(277 days)
Digni C3 system, DigniCap™, DigniCool™, DigniTherm™, DIGNISTICK™, DIGNICARD™
Not Found
No
The description focuses on a temperature control system and does not mention any AI or ML components for image analysis, data interpretation, or predictive capabilities. The system adjusts temperature based on sensor readings, which is a standard control loop, not AI/ML.
Yes
The device is indicated to "reduce the likelihood of chemotherapy induced alopecia," which is a therapeutic effect.
No
The device is designed to prevent chemotherapy-induced hair loss by cooling the scalp, which is a therapeutic rather than a diagnostic function. It does not measure or identify a disease or medical condition.
No
The device description clearly outlines multiple hardware components including a refrigerated tank, cooling unit, cap, thermometers, and a control system with a touch screen monitor. While software is mentioned for control and updates, the device is fundamentally a hardware system with integrated software.
Based on the provided information, the DigniCap™ Scalp Cooling System is not an IVD (In Vitro Diagnostic) device.
Here's why:
- Intended Use: The intended use is to "reduce the likelihood of chemotherapy induced alopecia in women with breast cancer." This is a therapeutic or preventative purpose, not a diagnostic one.
- Device Description: The device description details a system that physically cools the scalp. It does not involve the examination of specimens derived from the human body (like blood, urine, tissue, etc.) to provide information for the diagnosis, prevention, or treatment of a disease or condition.
- Lack of IVD Characteristics: The description does not mention any components or processes typically associated with IVD devices, such as reagents, assays, or analysis of biological samples.
- Performance Studies: The performance studies focus on the clinical outcome of hair loss reduction, not on the accuracy or reliability of a diagnostic test.
In summary, the DigniCap™ Scalp Cooling System is a medical device used for a therapeutic/preventative purpose (reducing hair loss), not for diagnosing a condition.
N/A
Intended Use / Indications for Use
The DigniCap™ Scalp Cooling System is indicated to reduce the likelihood of chemotherapy induced alopecia in women with breast cancer.
Product codes
PMC
Device Description
The Dignitana DigmiCap™ Scalp Cooling System consists of a computer controlled system that includes a refrigerated tank containing the cooling agent that is maintained at -8 ± 1 ℃. The liquid coolant circulates from the cooling unit to and through the channels of the cap and back to the cooling unit. The scalp temperature is monitored by three separate thermometers. Deviations from the pre-set temperature are automatically adjusted by the system (scalp temperature can be controlled with an accuracy of ±2.0℃).
The DigniCap™ Scalp Cooling System components include the following:
Digni C3 system - Is a refrigerator unit with an integral control system operated via a touch screen monitor and is capable of controlling two separate cooling caps independently of each other. Scalp cooling is performed in conjunction with a silicon inner cap (DigniCap™), an outer neoprene cap (DigniTherm™), and the liquid coolant (DigniCool™).
DigniCap™ - A soft, tight-fitting silicon cap which has two separate cooling circuits, one for the front of the head and one for the back of the head plus a third sensor for overall safety control.
DigniCool™ - The liquid coolant monopropylene glycol (MPG5).
DigniTherm™ - The outer neoprene cap that insulates and keeps the inner cap in place. To improve cooling and ensure proper fitting, this cap is covers the DigniCap™ and includes a chin strap which is used to hold the cap in place. This neoprene cover cap, called the DigniTherm™, comes in different sizes and is colored coded to match the corresponding correct silicone Cooling Cap. In addition to acting as a means of maintaining cooling cap placement, this outer cap also provides insulation which improves cooling efficiency
DIGNISTICK™ – A component used to save data from a treatment or for troubleshooting when inserted in the slot. It can also be used to update software.
DIGNICARD™ – A key card which has to be inserted in order to start a treatment.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Scalp
Indicated Patient Age Range
18 years of age and older.
Intended User / Care Setting
Prescription use in a medical setting.
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Not Found
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Feasibility Study
- Study Type: Feasibility Study
- Sample Size: 20 subjects, 2 sites
- Key Results:
- Primary endpoint: One patient out of 20 discontinued due to cap associated toxicity, resulting in a 5% discontinuation rate, indicating feasibility.
- Adverse events (Patient Reported): Head Pain (65%), Chill (80%), Scalp Pain (95%).
- Adverse events (Practitioner Reported): No cases of metastasis, including scalp metastasis. Adverse events (other than during time of actual cap use) were not related or unlikely related to cap use.
- Hair loss assessment (Patient assessment): Halfway through treatment, 60% of patients reported grade 2 alopecia.
- Hair loss assessment (Independent Panel assessment): Halfway through treatment, 85% of patients had 6. 43 patients reported headaches triggered/exacerbated by scalp cooling. Chilliness was reported by most patients (n=102 for cooling down, n=104 for overall treatment). Scalp pain was reported by 75 patients.
- Patient assessment of satisfaction with hair: Mean score of 70.9 (DigniCap™) vs 25.6 (control) for hair quantity. Mean score of 69.1 (DigniCap™) vs 37.6% (control) for hair quality. Mean score of 87.5 for satisfaction with decision to use scalp cooling.
- Quality of life (EORTC-QLQ-BR23): Increase in some symptom occurrences (dry mouth, painful eyes, hair loss, headaches, etc.) compared to baseline, but hair loss was twice as likely in the control arm.
- Adverse Events (SAEs): 8 patients experienced 9 unanticipated SAEs; none were related to scalp cooling (all chemotherapy related).
- Device Incidents: 22 incidents reported (cap malfunction, temperature sensor issues, cap not cooling, coolant leak).
- Subgroup Analysis (Effectiveness by Chemotherapeutic Regimen): Docetaxel and carboplatin (83.3% success), Docetaxel and cyclophosphamide (60.5% success), Paclitaxel (83.3% success).
- Subgroup Analysis (Effectiveness by Baseline Hair Quality): Thick hair (75% success), Medium hair (64% success), Thin Hair (82.4% success).
- No differences demonstrated when stratified by Age, BMI, prior history of chemotherapy.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Feasibility Study
- Discontinuation Rate due to cap associated patient toxicity: 5% (1 out of 20 patients)
- Hair loss grade 2 alopecia (Patient assessment): 55%
- Overall patients had
§ 878.4360 Scalp cooling system to reduce the likelihood of chemotherapy-induced alopecia.
(a)
Identification. A scalp cooling system to reduce the likelihood of chemotherapy-induced alopecia is a prescription device intended to reduce the frequency and severity of alopecia during chemotherapy in which alopecia-inducing chemotherapeutic agents are used.(b)
Classification —Class II (special controls). The special controls for this device are:(1) Non-clinical performance testing must demonstrate that the device meets all design specifications and performance requirements, and that the device performs as intended under anticipated conditions of use. This information must include testing to demonstrate accuracy of the temperature control mechanism.
(2) Performance testing must demonstrate the electromagnetic compatibility and electrical safety of the device.
(3) Software verification, validation, and hazard analysis must be performed.
(4) The patient contacting components of the device must be demonstrated to be biocompatible. Material names must be provided.
(5) Labeling must include the following:
(i) A statement describing the potential risk of developing scalp metastasis.
(ii) Information on the patient population and chemotherapeutic agents/regimen for which the device has been demonstrated to be effective.
(iii) A summary of the non-clinical and/or clinical testing pertinent to use of the device.
(iv) A summary of the device technical parameters, including temperature cooling range and duration of cooling.
(v) A summary of the device- and procedure-related adverse events pertinent to use of the device.
(vi) Information on how the device operates and the typical course of treatment.
(6) Patient labeling must be provided and must include:
(i) Relevant contraindications, warnings, precautions, and adverse effects/complications.
(ii) Information on how the device operates and the typical course of treatment.
(iii) Information on the patient population for which there is clinical evidence of effectiveness.
(iv) The potential risks and benefits associated with use of the device.
(v) Postoperative care instructions.
(vi) A statement describing the potential risk of developing scalp metastasis.
0
DE NOVO CLASSIFICATION REQUEST FOR DIGNICAP™ SCALP COOLING SYSTEM
REGULATORY INFORMATION
FDA identifies this generic type of device as:
Scalp cooling system to reduce the likelihood of chemotherapy induced alopecia: A scalp cooling system is intended to reduce the frequency and severity of alopecia during chemotherapy in which alopecia-inducing chemotherapeutic agents are used.
NEW REGULATION NUMBER: 878.4360
CLASSIFICATION: II
PRODUCT CODE: PMC
BACKGROUND
DEVICE NAME: DIGNICAP™ SCALP COOLING SYSTEM
SUBMISSION NUMBER: DEN150010
DATE OF DE NOVO: MARCH 6, 2015
CONTACT: DIGNITANA AB C/O GLEN D. PARK, PHARMD TARGET HEALTH, INC. 261 MADISON AVENUE, 24TH FLOOR NEW YORK, NEW YORK 10016
REQUESTER'S RECOMMENDED CLASSIFICATION: II
INDICATIONS FOR USE
The DigniCap™ Scalp Cooling System is indicated to reduce the likelihood of chemotherapy induced alopecia in women with breast cancer.
LIMITATIONS
The sale, distribution, and use of DigniCap™ Scalp Cooling System are restricted to prescription use in accordance with 21 CFR 801.109.
Limitations on device use are also achieved through the following statements included in the instructions for use:
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Contraindications:
"Contraindications are cold sensitivity, cold agglutinin disease, cryoglobulinemia and crvofibrinogenemia."
"Scalp cooling is contraindicated if chemotherapy is given with a curative intent in patients with hematological malignancies."
Precautions / Warnings:
"Long-term effects of scalp-cooling and scalp metastasis have not been fully studied"
"Use of scalp cooling with taxanes plus anthracyclines when used together or in sequence has not been shown to be successful in preventing chemotherapeutic drug induced alopecia."
"Attention: Clinical studies have produced variable success rates in patient reduction of chemotherapy induced alopecia with scalp cooling since the outcome is dependent on several factors including chemotherapy regimen, dose, duration of drug infusion, chemotherapy drug metabolism, and concomitant comorbidities."
"Breast cancer patients treated with taxanes plus anthracyclines, when used together or in sequence, have not been shown to respond to scalp cooling for reducing chemotherapeutic drug induced alopecia. Dignicap® Scalp Cooling System should not be used in these patients."
PLEASE REFER TO THE LABELING FOR A MORE COMPLETE LIST OF WARNINGS, PRECAUTIONS AND CONTRAINDICATIONS.
DEVICE DESCRIPTION
The Dignitana DigmiCap™ Scalp Cooling System consists of a computer controlled system that includes a refrigerated tank containing the cooling agent that is maintained at -8 ± 1 ℃. The liquid coolant circulates from the cooling unit to and through the channels of the cap and back to the cooling unit. The scalp temperature is monitored by three separate thermometers. Deviations from the pre-set temperature are automatically adjusted by the system (scalp temperature can be controlled with an accuracy of ±2.0℃).
The DigniCap™ Scalp Cooling System components include the following:
Digni C3 system - Is a refrigerator unit with an integral control system operated via a touch screen monitor and is capable of controlling two separate cooling caps independently of each other. Scalp cooling is performed in conjunction with a silicon inner cap (DigniCap™), an outer neoprene cap (DigniTherm™), and the liquid coolant (DigniCool™).
2
DigniCap™ - A soft, tight-fitting silicon cap which has two separate cooling circuits, one for the front of the head and one for the back of the head plus a third sensor for overall safety control.
DigniCool™ - The liquid coolant monopropylene glycol (MPG5).
DigniTherm™ - The outer neoprene cap that insulates and keeps the inner cap in place. To improve cooling and ensure proper fitting, this cap is covers the DigniCap™ and includes a chin strap which is used to hold the cap in place. This neoprene cover cap, called the DigniTherm™, comes in different sizes and is colored coded to match the corresponding correct silicone Cooling Cap. In addition to acting as a means of maintaining cooling cap placement, this outer cap also provides insulation which improves cooling efficiency
DIGNISTICK™ – A component used to save data from a treatment or for troubleshooting when inserted in the slot. It can also be used to update software.
DIGNICARD™ – A key card which has to be inserted in order to start a treatment.
Image /page/2/Picture/5 description: The image shows a medical device and four cooling caps. The medical device is a cooling machine on wheels with a screen and a red helmet-like attachment. The four cooling caps are different colors: yellow, green, blue, and red. The caps are designed to be worn on the head and have straps to secure them in place.
Figure 1: DigniTherm™ and corresponding DigniCap™
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SUMMARY OF NONCLINICAL/BENCH STUDIES
BIOCOMPATIBILITY/MATERIALS
The only portion the system that comes into patient contact is the silicon DigniCap™. The DigniCap™ is a surface device that is in contact with the skin for a limited duration (
75% hair loss by the completion of chemotherapy. | |
| Study
Endpoints | Primary endpoint:
To determine the feasibility of use of the DigniCap™ Scalp Cooling System in
this setting. Feasibility is defined as less than 50% of patients discontinuing use
of the cap due to cap associated patient toxicity.
Secondary endpoints:
- Ability to complete protocol case report forms
- Adverse events related to use of the DigniCap™ Scalp Cooling System
- Hair loss assessment in women receiving specified chemotherapy regimens
using the DigniCap™ Scalp Cooling System with success was defined as Exclusion criteria: | | |
| 1. | Patients must not have female pattern baldness resembling picture I-3 or higher on the Savin scale. | |
| 2. | No autoimmune disease affecting hair; e.g. alopecia areata, systemic lupus with associated hair loss. | |
| 3. | No history of whole brain radiation. | |
| 4. | No plan to use a chemotherapy regimen other than those specified in section 7. Specifically, patients receiving a regimen including both an anthracycline and a taxane are not eligible for this trial: : Adriamycin, Cytoxan/taxotere (AC/T), Epirubicin/cyclophosphamide/ taxotere (EC/T), Taxotere/Adriamycin/cyclophosphamide (TAC), etc.. Patients may not receive concurrent hormone therapy; hormone therapy should be given as indicated following completion of chemotherapy. | |
| 5. | No serious concurrent infection or medical illness which would jeopardize the ability of the patient to complete the planned chemotherapy. | |
| 6. | No history of persistent grade 2 alopecia induced by prior chemotherapeutic regimens. | |
| 7. | No participation in any other clinical investigation or exposure to other investigational agents, drugs, device or procedure that may cause hair loss. | |
| 8. | No intercurrent life-threatening malignancy. | |
| 9. | No history of cold agglutinin disease, cryoglobulinemia or | |
| | 10. No evidence of untreated or poorly controlled hyper or hypothyroidism. | |
| | 11. No history of silicon allergy. - No evidence of abnormal liver function, defined as, aspartate | |
| | aminotransferase (AST) ≥ 3x upper limit of normal. | |
| | 13. No evidence of abnormal kidney function defined as creatinine ≥ 2X upper | |
| | limit of normal. | |
| | 14. American Society of Anesthesiologist Class ≥3. | |
| Procedure | Eligible patients included women diagnosed with stage1 breast cancer planning
to receive chemotherapy in the adjuvant or neo-adjuvant setting. 20 patients
were enrolled. The majority (80%) received docetaxel and cyclophosphamide
(TC) every three weeks for four to six doses. Other chemotherapy regimens
included 12 cycles of weekly paclitaxel with trastuzumab (10%), and docetaxel
and carboplatin with trastuzumab every three weeks for six cycles (10%).
Patients will receive scalp hypothermia as delivered by the DigniCap™ Scalp
Cooling System. Scalp cooling will begin 30 minutes prior to administration of
chemotherapy. Scalp temperature will be maintained at +3°C (37°F) throughout
drug administration and for 90-120 minutes after discontinuing the infusion,
depending on the chemotherapy regimen | |
| | | |
| Follow-up | Safety and tolerability in terms of adverse symptoms and adverse device effects
reported by patients during use of the DigniCapTM Scalp Cooling System and
during the follow-up period 3, 6 and 12 months after completion of treatment
was examined. | |
| Assessment
Tools | Photographic documentation was performed before initiation of the first cycle
of chemotherapy, before each subsequent cycle, at a visit 3 to 4 weeks after the
last cycle of chemotherapy. | |
| | Hair loss was assessed by an independent panel consisting of a hair dresser, a
patient advocate, and a dermatologist specializing in hair according to the Dean
Scale by review of photographs blinded to patient and sequence. | |
| | Patients evaluated their degree of hair loss at each visit according to the Dean
Scale without the review of photographs. | |
| | Quality of Life during and after chemotherapy was assessed by the patient using
the European Organization for Research and Treatment of Cancer (EORTC)
Breast Cancer-Specific Quality of Life Questionnaire (QLQ-BR23) scale and the
Body Image Scale (BIS). | |
| | A Patient Symptom Survey was completed at each chemotherapy cycle. | |
| | | |
| Results | | |
| Patient | Evaluable patients for all follow-up visits = 19. | |
| Account- | | |
| ability | | |
| Results | Primary endpoint: | |
| | One patient out of the 20 evaluable patients discontinued study therapy due to
cap associated patient toxicity, patient assessed hair loss and severe anxiety. This
represents a 5% discontinuation rate and indicates that the scalp cooling system
is feasible in this setting. | |
| | Secondary endpoints | |
| | 1. Assessment of the ability to complete protocol case report forms
Patients completed a number of questionnaires throughout the study and
compliance was excellent | |
| | 2. Documentation of adverse events related to use of the DigniCap™ System | |
| | 2.1 Patient Reported Symptoms
Head Pain - 65% (13) of patients reported head pain during at least one
treatment
Chill - 80% (18) of patients experienced chill during treatment.
Scalp Pain - 95% (19) of patients reported scalp pain during at least one
treatment.
2.2 Use of Pain Medications During Treatment immediately before their
chemotherapy infusion and use of the DigniCap™ Scalp Cooling System
at some point during their treatment course
3 patients (15%) took non-prescription pain medication
11 patients (55%) took prescription pain medication
7 patients (35%) reported not using pain medication of any kind the
morning of their infusion with the DigniCap™ Scalp Cooling System
2.3 Practitioner reported specific cap-related adverse events.
No cases of metastasis, including metastasis to the scalp.
Adverse events (other than during time of actual cap use) were not related or
unlikely related to cap use. | |
| | 3. Hair loss assessment in women receiving specified chemotherapy
regimens using the DigniCap™ Scalp Cooling System including: | |
| | 3.1 Patient assessment
3.1.1. Assessment of physical hair loss according to the Deans scale.
Baseline mean grade on Deans scale = 0.15.
Halfway through treatment (N=20): 60% of patients reported grade 2 alopecia throughout their entire treatment and follow-up. | |
| | 3.1.2. Assessment of quality of treatment response & quality of life. | |
| | 3.1.3. Assessment of the impact of hair loss on treatment decisions | |
| 3.2. Assessment by independent panel | | |
| - | Halfway through treatment (N=20): 85% of patients had 4. Quality of life in women using the DigniCap™ System: | | |
| | Overall, average patient satisfaction with hair was 85% at baseline, and 82% three months after the completion of chemotherapy. At the 1 month follow up the use of wigs was reported as "always" in 11% of patients, “sometimes" in 16% of patients and "never" in 74% of patients. The percentage of patients who strongly agreed that their hair was important to them was 80% at Baseline and 81% at 1 month follow up. The percentage of patients who thought that their hair was important to their appearance increased from 74% at Baseline to 93% at 1 month follow up. | |
| 5. Impact of hair loss on treatment decisions | | |
| - | Seventy-five percent of patients said hair loss did not affect their decision at all or it affected it a little. | |
| - | Overall, 17 (85%) of the participants commented at least once that the availability of the scalp cooling system made their decision much easier: they were grateful for the scalp cooling option, and/or that the opportunity relieved some of the stress involved in the decision. | |
Table 3: Feasibility Study
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Feasibility Study Summary:
This feasibility study consisted of 20 patients from 2 centers with stage 1 breast cancer who were to receive alopecia inducing chemotherapeutic regimens. The patients were followed for one year. The objective of this study was to demonstrate that these breast cancer patients who would normally have a greater than 75% hair loss with chemotherapy, had a reduction in the incidence and frequency of hair loss with hypothermia treatment of the scalp. The DigniCap™ Scalp Cooling System was shown to decrease hair loss by over 50% in 75% of the patients. This benefit was associated with minor risks and side effects: 65% of patients experienced headaches, 80% experienced chills, and 95% of patients reported scalp pain during at least one treatment. The side effects usually resolved with termination of scalp cooling and there were no incidence of scalp metastasis during the one year follow-up. Only one patient dropped out of the study due to anxiety
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and failed hair preservation. No serious adverse events or safety issues were attributed to DigniCap™ Scalp Cooling System in this feasibility study. Patient overall satisfaction with the quality and quantity of their hair was 85% at baseline and 82% three months after the completion of chemotherapy and 74% never had to use a wig. The presence of a scalp cooling system made the decision to undergo chemotherapy much easier in 85% of the patients.
Table 4: Pivotal Study
| Table 4: Pivotal Study | |
|---|---|
| Study | |
| Title | Clinical Performance, Efficacy and Safety of the DigniCap™ Scalp Cooling |
| System, a Scalp Hypothermia System, in Preventing Chemotherapy Induced | |
| Alopecia in Patients with Early Stage Breast Cancer | |
| Study | |
| Design | This study was a non-randomized, multi-center (6 sites), concurrent controlled, |
| clinical study to evaluate the effect of scalp cooling on hair loss during treatment | |
| with alopecia inducing chemotherapeutic regimens. | |
| Study | |
| Objectives | The overall objective is to assess the clinical performance, efficacy and safety of a |
| Scalp Hypothermia System in breast cancer patients receiving specific | |
| chemotherapy treatments that, unless counteracted by simultaneous hypothermia | |
| treatment, result in hair loss. | |
| Primary Objective: |
- To assess the ability of the DigniCap™ Scalp Cooling System to prevent
hair loss in women receiving specific chemotherapy regimens for early
stage breast cancer. Efficacy will be measured by assessment of hair loss up
to 4 weeks (3-6 week window) after the completion of the last
chemotherapy cycle by patient self-assessment of standardized
photographs using the Dean scale by patients in the treatment and control
groups |
| | Secondary Objectives: - To assess safety of the DigniCap™ Scalp Cooling System in women
receiving specific chemotherapy regimens for early stage breast cancer. - To assess tolerability of the DigniCap™ Scalp Cooling System.
- To evaluate hair loss and recovery as assessed by the patient during and
following chemotherapy using the alopecia self-report. - To evaluate hair re-growth at 3 and 6 months after completion of
chemotherapy as assessed by the patient using the Hair Re-growth Follow
Up Survey. - To assess patient quality of life and satisfaction with hair during and after
treatment with the DigniCap™ Scalp Cooling System. - To assess the impact of hair loss on treatment decisions. |
| Study
Endpoints | Primary endpoint:
Success of the DigniCap™ Scalp Cooling System to prevent hair loss, defined as a
maximum Dean score of ≤ 2 using standardized photographs graded by the patient
up to 4 weeks after the last chemotherapy treatment, in at least 50% of patients |
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| enrolled in the treatment group with a lower bound of the 95% CI greater than | |||||
|---|---|---|---|---|---|
| 40%, and statistical superiority over a concurrent control group. | |||||
| Secondary endpoints: | |||||
| 1. Safety as determined by spontaneous reporting of adverse events and as negative scalp changes determined by physical examination. | |||||
| 2. Tolerability is defined as the percentage of patients who complete all planned cycles of chemotherapy do so using the DigniCap™ Scalp Cooling System. | |||||
| 3. Patient assessment of hair loss by the alopecia self-reports at each chemotherapy. Hair re-growth is defined an improvement in the Dean scale by at least one level. | |||||
| 4. Quality of life as measured by the EORTC-QLQ-BR23 quality of life questionnaire and a Body Image Scale. | |||||
| Number of Patients/ Sites | Treatment subjects: n=110 (Presumed drop-out rate of 10% results in n=100); | ||||
| Control subjects: n=15 (at interim analysis) or 30 | |||||
| 5 sites | |||||
| Inclusion/ Exclusion Criteria | Inclusion | ||||
| 1. Female patients 18 years of age | |||||
| 2. Documented diagnosis of stage I or II breast cancer | |||||
| 3. A planned course of chemotherapy in the adjuvant or neoadjuvant setting with curative intent including one of the following regimens: | |||||
| - Doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 x 4 - 6 cycles IV every 2 - 3 weeks | |||||
| - Docetaxel 75 mg/m2 and cyclophosphamide 600 mg/m2 x 4 - 6 cycles IV every 3 weeks | |||||
| - Paclitaxel 80 mg/m2 weekly IV x at least 12 weeks with or without IV trastuzumab | |||||
| - Paclitaxel 175 mg/m2 IV every 2 weeks x 4 – 6 cycles (without an anthracycline) | |||||
| - Paclitaxel weekly and carboplatin AUC 2 weekly or AUC 6 every 3 weeks IV x 4 - 6 cycles with or without trastuzumab IV weekly or every 3 weeks | |||||
| - Docetaxel 75 mg/m2 and carboplatin AUC 6 IV every 3 weeks x 4 - 6 cycles with or without trastuzumab IV weekly or every 3 weeks | |||||
| - Targeted agents such as trastuzumab or lapatinib are allowed | |||||
| 4. Plan to complete chemotherapy within 6 months | |||||
| 5. At least two years out from the last chemotherapy causing hair loss with complete recovery of hair | |||||
| 6. Karnofsky performance status 80% | |||||
| 7. Willing and able to sign informed consent for protocol treatment | |||||
| 8. Willing to participate in study procedures including having photographs of the head before each cycle of chemotherapy and 1 month after the last chemotherapy | |||||
| 9. Willing to enroll in an extension protocol for follow up for 5 years following the end of chemotherapy |
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| Exclusion | 1. Patients with female pattern baldness resembling picture 1-3 or higher on the Savin scale
2. Autoimmune disease affecting hair; e.g. alopecia areata, systemic lupus with associated hair loss
3. Plans to use a chemotherapy regimen other than those specified in the inclusion criteria. Specifically, patients receiving a regimen including both an anthracycline and a taxane are not eligible for this trial: AC/T, EC/T, TAC, etc.
4. A history of whole brain radiation
5. Concurrent hormone therapy with chemotherapy. Hormone therapy should be used as indicated following completion of chemotherapy
6. Intercurrent life-threatening malignancy
7. Clinically significant renal dysfunction defined as serum creatinine > the upper limit of normal
8. Underlying clinically significant liver disease including active viral hepatitis with abnormal liver function tests >1.5 times the upper limit of normal, including alkaline phosphatase, AST, and total bilirubin. Patients with Gilbert's disease (elevated indirect bilirubin only) will be eligible for participation.
9. A serious concurrent infection or medical illness that would jeopardize the ability of the patient to complete the planned therapy and follow-up
10. A history of persistent grade 2 (or higher) alopecia induced by prior chemotherapeutic regimens
11. A history of cold agglutinin disease or cryoglobulinemia
12. Evidence of untreated or poorly controlled hyper- or hypothyroidism
13. A history of silicon allergy
14. American Society of Anesthesiologist Class ≥3 |
| ----------- | ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- |
|---|
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| Taxotere carboplatin (TC) x 4 or 6 cycles, every 3 weeks | Docetaxel 75 mg/m², Cyclophosphamide 600 mg/m² | 120 |
|---|---|---|
| Paclitaxel x at least 12 cycles every week | Paclitaxel 80 mg/m² | 90 |
| Paclitaxel and Carboplatin x 6 cycles, 3 on / 1 off | Paclitaxel weekly and carboplatin AUC 2 weekly or AUC 6 every 3 weeks IV x 4 - 6 cycles with or without trastuzumab IV weekly or every 3 weeks | 120 |
| Paclitaxel x 4 – 6 cycles every 2 weeks | Paclitaxel 175 mg/m² IV every 2 weeks (without an anthracycline) | 120 |
| Taxotere, carboplatin herceptin (TCH) x 6 cycles every 3 weeks (pertuzumab is allowed in the neoadjuvant setting) | Docetaxel 75mg/m², Carboplatin AUC 6, Trastuzumab weekly or every 3 weeks | 120 |
| Pertuzumab, trastuzumab, and docetaxel every 3 weeks (in the neoadjuvant setting) for 3 - 6 cycles | Pertuzumab initial dose of 840 mg, followed by 420 mg every 3 weeks, Trastuzumab initial dose of 8 mg/kg, followed by 6 mg/kg every 3 weeks, Docetaxel 75 mg/m² | 120 |
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| | 2.
EORTC-QLQ-BR23 was used to assess at baseline, cycle 4 and 4 weeks | | | |
|---------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------|-------------------------|--|
| | after the last cycle of chemotherapy.
3. | | | |
| | Body Image Scale (BIS) was done at Baseline, Cycle 4 of chemotherapy and
4 weeks after the last cycle of chemotherapy. | | | |
| | 4.
Hair re-growth was evaluated at Month 3 and 6 post completion of | | | |
| | | chemotherapy. For this the patient graded their hair quality in terms of | | |
| | texture, manageability, and color variation from baseline. | | | |
| | Photographic Documentation: Photographic documentation for all treatment and
control patients will be performed before initiation of the first cycle of
chemotherapy, each subsequent cycle of chemotherapy, and at a visit 4 weeks (3-6
week window) after the last cycle of chemotherapy. At each time point, 5
photographs should be taken: from the front (bangs should be held back), behind,
both sides and the top with the hair divided in the midline with both hands.
Hair loss will be assessed by comparing the photographs against standardized
photographs to estimate the percentage of hair lost according to the Dean scale.
At the end of the infusion:
Discomforts such as headache, being chilled, and scalp pain will be assessed using | | | |
| | a visual analogue scale. Any adverse events will also be reported. | | | |
| Follow-up | Adverse Device Events (ADE)
An Adverse Device Event is any untoward and unintended response to a medical
device, including any event resulting from insufficiencies or inadequacies in the
instructions for use of the device, and/or any event that is a result of a user error.
The outcome of the adverse event will be assessed as:
1 = Resolved
2 = Improved
3= Unchanged
4= Worse
5= Fatal
6= Not available
The action taken as a result of the adverse event will be assessed as:
1 = None
2 = Therapy required
3= Procedure discontinued due to AE
4= Hospitalization required or prolonged | | | |
| | | Results | | |
| Patient | | | | |
| Account-
ability | | Treated Group
(N=106) | Control Group
(N=16) | |
| | Safety Population | IOQ | ] ୧ | |
| | Evaluable | 101 | ાર | |
| | Per Protocol | ૪૨ | ા ર | |
16
| | | Patients discontinued use of the cap due to :
4 patients were excluded from the evaluable population due to toxicity of chemotherapy. 1 patient was excluded from the evaluable population due to eligibility violation. 8 patients discontinued due to hair loss 1 patient withdrew because of the length of time of the study and the coldness was unbearable 2 patients refused after one cycle due to the effect of cooling during and after chemotherapy 4 patients discontinued due to non-compliance 1 patient was lost to follow-up | | |
|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------|-----------------|
| Patient
Demographics | | | DigniCapTM
N=106 | Control
N=16 |
| | Age | N | 106 | 16 |
| | | Mean | 53.0 | 54.9 |
| | | SD | 11.2 | 8.6 |
| | | Median | 55.0 | 56.0 |
| | | Minimum | 28.0 | 36.0 |
| | | Maximum | 77.0 | 67.0 |
| | Ethnicity | N | 106 | 16 |
| | | Hispanic or Latino | 17 (16.0%) | 1 (6.3%) |
| | | Not Hispanic or Latino | 88 (83.0%) | 15 (93.8%) |
| | | Missing | 1 (0.9%) | 0 (0.0%) |
| | Race | N | 106 | 16 |
| | | American Indian or Alaska Native | 0 (0.0%) | 0 (0.0%) |
| | | Asian | 10 (9.4%) | 3 (18.8%) |
| | | Black or African | 11 (10.4%) | 0 (0.0%) |
| | | Native Hawaiian or Other Pacific | 0 (0.0%) | 0 (0.0%) |
| | | White | 82 (77.4%) | 12 (75.0%) |
| | | Multiracial | 1 (0.9%) | 1 (6.3%) |
| | | Missing | 2 (1.9%) | 0 (0.0%) |
| Note: Two subjects have multiracial background. Subject 03-C002 is American Indian or Alaska Native, Black or African American, White. Subject 03-T023 is Native Hawaiian or Pacific Islander White | | | | |
17
| Primary
Effectiveness | Of the 101 evaluable patients in the DigniCap™ Scalp Cooling System treatment
group, 67 (66.3%) demonstrated treatment success (Dean score ≤2) compared to | | |
|--------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------|------------|
| S | 0 (0%) in the control group who did not use the DigniCap™ Scalp Cooling | | |
| | System (95% CI, 56.2, 75.4%; p 25% up to 50% hair
loss) | 31 (30.7%) | 0 |
| | Grade 3 (>50% up to 75% hair
loss) | 19 (18.8%) | 1 (6.3%) |
| | Grade 4 (>75% hair loss)
below. | 15 (14.9%) | 15 (93.8%) |
| | An independent panel review of the photographs was conducted and 73 patients
(72%) were rated as treatment successes. | | |
| Secondary
Endpoints | Tolerability is defined as the percentage of patients who complete all
planned cycles of chemotherapy do so using the DigniCap™ Scalp Cooling
System | | |
| | 83.0% of patients completed all planned cycles of chemotherapy using the
DigniCap™ System in all cycles | | |
| | Patient Symptoms Survey: looked at tolerability of the cap with respect to
headaches, scalp pain and the feeling of chilling due to the cap. | | |
| | Patient Symptoms Survey results showed that 74 patients experienced
headaches during the prior month; 31.1% of the patients had 1-2
headaches, 27.0% had 3-4 headaches, 21.6% had 5-6 headaches, and
20.3% had >6 headaches. A total of 43 patients reported that headaches were triggered or
exacerbated by scalp cooling treatment and the average level of pain
experienced by these patients was 39.3 on a scale of 0 to 100 (with 100
being the worst pain). On average this occurred for 1 cycle but ranged up
to 10 cycles. There were over 100 instances reported. The feeling of chilliness during the cooling down period was reported by
most patients (n=102) and with overall cooling treatment (n=104). Scalp pain associated with cooling was reported by 75 patients with an
average level of any scalp pain experienced by these patients of 24.2 out
of 100 (range 1.7 to 85.0). Over 250 instances of scalp pain were | | |
18
recorded.
-
. Of the 105 patients, only 35 took pain medications during the chemotherapy cycles.
Patient assessment of satisfaction with their hair by the alopecia self-reports at each chemotherapy. -
A mean score of 70.9 out of 100 for satisfaction for hair quantity in the ● DigniCap™ Scalp Cooling System group versus 25.6 in the control group.
-
. A mean score of 69.1 out of 100 for satisfaction with hair quality in the DigniCap™ Scalp Cooling System group versus 37.6% in the control group.
-
. A mean score of 87.5 out of 100 for satisfaction with decision to use scalp cooling.
Quality of life as measured by the EORTC-QLQ-BR23 quality of life questionnaire and a Body Image Scale.
On the EORTC questionnaire:
- a) There was an increase in the number of patients from baseline at the last cycle of chemotherapy and one month follow-up that had dry mouth, different than usual taste in food and drink, eyes were painful, irritated or waterv, lost hair, upset at hair loss, feel ill or unwell, have hot flushes. have headaches, felt physically less attractive or less feminine due to the disease or treatment. However, hair loss was twice as likely to occur in the control arm as the treatment arm.
- b) There were less changes from baseline in the number of patients in responses to the categories of difficult to look at yourself naked, dissatisfied with body imaging, worried about heath in the future, interested in sex, extent of being sexually active, sexually enjoyable, pain or swollen in the arm or shoulder, difficult in raise arm or move it sideways, if pain, swollen, oversensitive or skin problem (itchy, dry flaky) in affected breast at the last cycle of chemotherapy and one month followup
On the Body Image Scale questionnaire:
Greater than 90% of patients in the DigniCap™ Scalp Cooling System treatment group agreed strongly and somewhat that hair is important and is important for appearance compared to 90% in the Control Group at the end of the study period. Note that at baseline in the control group 75% felt strongly.
To look further at the question of headaches, the EORTC-QLQ-BR23 also included a question regarding the frequency of headaches compared to baseline and is presented below. Of note is that the control group and a much higher rate change in response to this question than did the treated group. So although, headache may have been associated with use of the device the effect dissipated once the device was no longer used. The number of patients having a headache in
19
| the treated group was nearly double the baseline at last assessment, while the control group remained the same. | ||||
|---|---|---|---|---|
| Adverse | ||||
| Events | 1. Eight (8) patients experienced 9 unanticipated SAEs; two (2) patients who discontinued from the study due to an AE |
- Patients events that were suspected or probably related to DigniCap™ Scalp Cooling System treatment, included:
• Headache (4)
• Pruritus (1)
• Pain of skin (1)
• Head discomfort (1)
• 1 instance of neck pain which is listed as mild serverity | | | |
| | Summary of SAE's: (There were no deaths) - There were 5 unanticipated events in 4 patients in the treatment group and 4 events in the control group.
- None of the SAE's were related to scalp cooling.
- All were chemotherapy related and not unexpected. They included: febrile neutropenia, anemia, thrombocytopenia and a maculo-papular rash.
- All required hospitalization and intervention but all resolved.
- Two (2) patients discontinued from the study due to an unrelated to device AE, one (02-T010) experienced an allergic reaction, shortness of breath and facial flushing on 18Mar2014; the infusion was interrupted, the patient required oxygen. This hypersensitivity reaction (immune system disorders) recovered/resolved in one month. One patient (03-T024) experienced peripheral neuropathy, numbness in fingertips and toes on 11Apr2014. This event (nervous system disorders) recovered/resolved in two months. | | | |
| | Device Incidents: (There were 22 device incidents during the trial ) - Most common was cap malfunction (n=11)
- Problems with the temperature sensor/cooling cable not working (n=9)
- Cap never cooling down (n=4)
- 1 event of coolant leaking was identified | | | |
20
| Subgroup | Effectiveness by Chemotherapeutic Regimen: | ||||||
|---|---|---|---|---|---|---|---|
| Analyses | n | Success Rate | 95% CI (%) | p-value | |||
| Docetaxel and | |||||||
| carboplatin | 12 | (%) | |||||
| 83.3 | 51.6, 97.9 | 0.022 | |||||
| Docetaxal and | |||||||
| cyclophosphamide | 76 | 60.5 | 48.6, 71.6 |