DigniCap Scalp Cooling System

{0}------------------------------------------------ Image /page/0/Picture/2 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is an abstract symbol that resembles three human profiles facing to the right, with flowing lines beneath them. Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002 July 3, 2017 Dignitana AB % Mr. Michael Billig Experien Group, LLC 224 Airport Parkway. Suite 250 San Jose, California 95110 Re: K170871 Trade/Device Name: DigniCap Scalp Cooling System Regulation Number: 21 CFR 878.4360 Regulation Name: Scalp Cooling System to Reduce the Likelihood of Chemotherapy Induced Alopecia Regulatory Class: Class II Product Code: PMC Dated: March 21, 2017 Received: March 23, 2017 Dear Mr. Billig: We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Actinclude requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading. If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register. Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR {1}------------------------------------------------ Part 807); labeling (21 CFR Part 801); medical device reporting (reporting of medical devicerelated adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050. If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance. You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. Sincerely. # Jennifer R. Stevenson -S3 For Binita S. Ashar, M.D., M.B.A., F.A.C.S. Director Division of Surgical Devices Office of Device Evaluation Center for Devices and Radiological Health Enclosure {2}------------------------------------------------ # Indications for Use 510(k) Number (if known) K170871 Device Name DigniCap® Scalp Cooling System Indications for Use (Describe) The DigniCap® Scalp Cooling System is indicated to reduce the likelihood of chemotherapy-induced alopecia in cancer patients with solid tumors. Type of Use (Select one or both, as applicable) X Prescription Use (Part 21 CFR 801 Subpart D) | Over-The-Counter Use (21 CFR 801 Subpart C) #### CONTINUE ON A SEPARATE PAGE IF NEEDED. 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Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to: > Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff@fda.hhs.gov "An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number." {3}------------------------------------------------ K170871 510(k) Notification DigniCap® Scalp Cooling System Page 1 of 15 #### 510(k) Summary (K170871) ## Applicant Dignitana AB Traktorgränden 3 Lund, Sweden SE-226 60 Phone: +46 46 16 30 92 Fax: +46 46 16 30 99 Johan Ericsson, CEO johan.ericsson@dignitana.se ## Contact Person: Michael J. Billig, CEO Experien Group LLC Regulatory Consultant to Dignitana AB 224 Airport Parkway, Suite 250 San Jose, CA 95110 Tel: (408) 400-0856 Fax: (408) 400-0865 mjb@experiengroup.com ### Date of Summary: June 20, 2017 | Device Proprietary Name | DigniCap® Scalp Cooling System | | | |--------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------|--------------| | Common/Usual Name | Scalp Cooling System | | | | Classification Names /<br>Numbers and Code | 21 CFR | Classification Name | Product Code | | | 878.4360 | Scalp Cooling System | PMC | | Regulatory Class | II | | | | Prescription Status | Prescription Device | | | | Device / Classification<br>Panel | General & Plastic Surgery | | | | Predicate Device | DigniCap® Scalp Cooling System DEN150010 | | | | Description of Device | The DigniCap® Scalp Cooling System consists of a computer<br>controlled system that includes a refrigerated tank containing the<br>liquid coolant that is maintained at -7 $\pm$ 2°C. The coolant<br>circulates from the cooling unit to and through the channels of the<br>cap and back to the cooling unit. The scalp temperature is<br>monitored by three separate sensors. Deviations from the<br>treatment temperature are automatically adjusted by the system<br>(scalp temperature can be controlled with an accuracy of $\pm$ 2.0°C).<br>The DigniCap® Scalp Cooling System components include the<br>following: | | | {4}------------------------------------------------ | Description of Device (cont.) | Digni C3 – Is a refrigerator unit with an integral control system<br>operated via a touch screen and is capable of controlling two<br>separate DigniCap® Cooling caps independently of each other.<br>Scalp cooling is performed in conjunction with a silicone inner<br>cap (DigniCap®), an outer neoprene cap (DigniTherm), and the<br>liquid coolant (DigniCool). | |-------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------| | | DigniCap® – A soft, tight-fitting silicone cap which has two<br>separate cooling circuits, one for the front and one for the back of<br>the head. Each cooling circuit is equipped with a temperature<br>sensor, and the cap is also equipped with a third sensor for safety<br>control. The cap is available in different sizes. | | | DigniCool - The liquid coolant monopropylene glycol. | | | DigniTherm - The outer neoprene cap that insulates and keeps<br>the inner cap in place. This neoprene cover cap, called the<br>DigniTherm, comes in different sizes and is colored coded to<br>match the corresponding DigniCap® Cooling cap. | | | DigniStick- A component used to save data from a treatment or<br>for troubleshooting. It can also be used to update software. | | | DigniCard - A key card which has to be inserted in order to start<br>a treatment. | | Indications for Use | The DigniCap® Scalp Cooling System is indicated to reduce the<br>likelihood of chemotherapy-induced alopecia in cancer patients<br>with solid tumors. | ### 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: ## Contraindications The use of Dignicap is contraindicated in pediatric patients. The use of Dignicap is contraindicated in adult patients with: - cold sensitivity, - cold agglutinin disease, ● - cryoglobulinemia ● - cryofibrinogenemia. ● - Cold urticaria - CNS malignancies (either primary or metastatic), - squamous cell carcinoma of the lung, - small cell carcinoma of the lung, - cancers of the head and neck, ● - skin cancers including melanoma, squamous cell carcinoma, and Merkel cell ● carcinoma. - hematological malignancies treated with curative intent by chemotherapy ● {5}------------------------------------------------ K170871 510(k) Notification DigniCap® Scalp Cooling System Page 3 of 15 - solid tumor malignancies with a high likelihood of metastases in transit. - patients who are scheduled for bone marrow ablation chemotherapy - patients who are scheduled to undergo skull irradiation ● - patients who have previously received skull irradiation #### Warnings Scalp and/or cutaneous metastases have been reported in patients with non-small cell lung cancer, colon cancer, renal cell carcinoma, ovarian cancer, and bladder cancer. Patients with advanced forms of these cancers may be more likely to experience scalp metastases with the scalp cooling svstem. Use of Scalp Cooling in the palliative setting in patients with metastatic cancer may also increase the risk for scalp metastases. Use of scalp cooling with taxanes plus anthracyclines when used in combination has not been shown to be successful in preventing chemotherapeutic drug induced alopecia. Dignicap® Scalp Cooling System should not be used in these patients. Scalp radiation can cause stenosis of small cutaneous vessels decreasing device effectiveness. The effectiveness of this device in patients who have received previous chemotherapy has not been evaluated. The risk of scalp-cooling may outweigh the benefits in patients receiving chemotherapeutic agents with low incidence of inducing alopecia. Long-term effects of scalp-cooling and risk of scalp metastasis have not been fully studied. Clinical studies have demonstrated variable success rates in patient reduction of chemotherapy induced alopecia with scalp cooling since the outcome is dependent on multiple factors including chemotherapy regimen, dose, duration of drug infusion, chemotherapy drug metabolism, and concomitant comorbidities. Data have shown that women who experience hair loss in spite of using scalp cooling might have worse quality of life than women who did not have scalp cooling. #### Comparison to Predicate Devices Aside from the change in the Indications for Use, the DigniCap® Scalp Cooling System is identical in technological characteristics, design and performance to the predicate. #### Summary of Testing #### Pre-clinical Testing No additional testing was conducted for this 510(k) to support substantial equivalence. The device in this submission is identical to the previously cleared device, as the purpose of this application was for the expansion of the treatment population only. Testing of the predicate device included biocompatibility, shelf-life, shipping and packaging, electromagnetic compatibility and electrical safety, software, bench testing, and two clinical studies. All tests met the pre-determined specifications and acceptance criteria and demonstrated the DigniCap® Scalp Cooling System to be safe and effective as labeled. {6}------------------------------------------------ K170871 510(k) Notification DigniCap® Scalp Cooling System Page 4 of 15 #### Clinical Data The efficacy of scalp cooling with the DigniCap System has been reported in 18 clinical evaluations outside of the U.S. These studies investigated the effects of scalp cooling on the incidence of alopecia in patients with various malignancies using a variety of chemotherapy regimens in both the adjuvant and palliative settings. Efficacy has best been demonstrated in chemotherapy regimens containing docetaxel, paclitaxel, cyclophosphamide, and/or carboplatin. These studies did not have long term follow up, and were single armed non-randomized prospective studies. Long-term effects of scalp-cooling and scalp metastasis have not been fully studied in the adjuvant setting outside of stage I and II breast cancer. It is not clear whether there is increased risk of recurrence, particularly scalp or skull metastases, based on the data available. Some of the studies did not list the names of the solid tumor malignancies or their frequencies. A literature review was conducted to address the safety and effectiveness of the DigniCap device. A search in PubMed, EMBASE, Clinical Trial register and Manufacturer and User Facility Device Experience Database - (MAUDE) was performed using the following search terms: DigniCap, Digni and scalp, Digni and alopecia, Digni and hypothermia, and Dignitana. Abstracts and peer reviewed articles (Table 1) of clinical trials covering the majority of the relevance and methodology questions in the appraisal plan of the pivotal clinical evaluation report were selected. Due to the literature review method and the design of these studies, safety and effectiveness results presented in these studies may not be accurate. Based on the above published data there is insufficient evidence to assess long term effect. Use of DigniCap Scalp Cooling System in these patients may increase the risk of scalp metastasis, metastasis elsewhere in the body or impact the natural course of the disease #### Conclusion The DigniCap Cooling System described in this application is unchanged from the device approved in DEN150010. This application is limited to a revision of the indication for use. The clinical data described in the literature documents provided in this application do demonstrate that the DigniCap Cooling System can be used to reduce the likelihood of chemotherapy-induced alopecia in cancer patients with solid tumors. {7}------------------------------------------------ # Table 1 # Clinical Data with the DigniCap® Scalp Cooling System Outside of U.S. | Publication<br>(author, year,<br>institution) | Type of study<br>(RCT, retrospective,<br>single arm<br>prospective<br>nonrandomized<br>studies.) | Treatment group | Control group | Sample size | Length of<br>Follow- up | Follow-up schedule | Completed Cooling<br>% | % Success with<br><50% hair loss | List of Adverse<br>Events | Reason for<br>discontinuation<br>of cooling | |-----------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------|----------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------| | Hernández et al., 2016<br>American British<br>Cowdray, ABC Medical<br>Center, Mexico City | Retrospective<br>Consecutive series of<br>patients;<br>December 2010 -<br>January 2015. | Weekly TX for 12 cycles<br>(n=4).<br>Weekly TX for 12 cycles and<br>AC every 3 weeks for 4-6<br>cycles (n=66).<br>AC every 3 weeks for 6-8<br>cycles (n=28). | N/A | 204 patients with<br>Stage I-V breast<br>(n=120), ovary,<br>lung, uterus,<br>esophagus,<br>prostate, chest,<br>urethra, rectum,<br>larynx, bladder,<br>colon, liver cancer<br>and non-Hodgkin´s<br>lymphoma. | Not stated | Hair loss - Photos<br>Dean scale | 72% (98/120) | 84% (82/98) | At follow-up:<br>no side effects<br>or scalp<br>metastasis<br>present. | Hair loss. | | Fehr et al., 2016<br>1. Clinic of Kempten-<br>Oberallgäu, Germany<br>2. Cantonal Hospital<br>Frauenfeld, Switzerland | Non randomized<br>prospective | PT 175 mg/m2 and<br>carboplatin 6 AUC (area<br>under the curve) for 6 three-<br>week cycles [n = 12 (22%)]<br>D 60 mg/m2 and C 600<br>mg/m2 for 4 three-week<br>cycles, followed by DT 100<br>mg/m2 for 4 three-week<br>cycles [n = 11 (20%)]<br>E 90 mg/m2 and C 600<br>mg/m2 for 4 three-week<br>cycles, followed by PT 80<br>mg/m2 weekly for 12 weeks<br>[n = 10 (18%)]<br>PT 80 mg/m2 weekly for 16<br>weeks [n = 8 (15%)]<br>DT 75 mg/m2 and C 500<br>mg/m2 for 4 three-week<br>cycles [n = 6 (11%)]<br>F 500 mg/m2, E 100 mg/m2,<br>and C 500 mg/m2 for 3 three-<br>week cycles, followed by DT<br>100 mg/m2 for 3 three-week<br>cycles [n = 64 (7%)]<br>DT 75 mg/m2, D 50 mg/m2,<br>and C 500 mg/m2 for 6<br>three-week cycles [n = 4 (7%) | N/A | Women with breast,<br>endometrial, or<br>ovarian cancer<br>(n=55)<br>Breast cancer<br>35adjuvant,<br>5 palliative,<br>2 neo- adjuvant<br>Ovarian cancer 12<br>(22%)<br>Endometrial cancer<br>1 patient (1.8%) | Not stated | Photographs of the<br>patient's head from<br>5 different views.<br>WHO scale.<br>Grade 0: no hair loss<br>Grade 1: minimal<br>hair loss (>0% to<br>25%).<br>Corresponds to<br>Dean score 0 and 1. | 78% (43/55) | 56% (28/50)<br>(up to 25% hair<br>loss) | 1.8% (1/55)<br>could not<br>tolerate scalp<br>cooling. | Hair loss (n=7),<br>death (n=3),<br>change of treatment<br>centre (n=1),<br>and doubts about<br>study participation<br>resulting in withdrawal<br>of consent within 30<br>minutes of initiation of<br>the 1st cycle (n=1). | | Publication<br>(author, year,<br>institution) | Type of study<br>(RCT, retrospective,<br>single arm<br>prospective<br>nonrandomized<br>studies. | Treatment group | Control group | Sample size | Length of<br>Follow- up | Follow-up schedule | Completed Cooling<br>% | % Success with<br><50% hair loss | List of Adverse<br>Events | Reason for<br>discontinuation<br>of cooling | | Drinkut et al., 2016<br>Medizinische<br>Hochschule Hannover,<br>Klinik für<br>Frauenheilkunde und<br>Geburtshilfe, Hannover,<br>Germany | Non randomized<br>prospective<br>June 2014 - February<br>2016 | 4 x E/C 90/600 mg/m2 + 12 x<br>PT 80 mg/m2 | N/A | Women with breast<br>cancer (n=34) | Not stated | Quantification of<br>hair loss by patients<br>and nursing staff.<br>Photos. | 56% (19/34) | 100%<br>(Patient<br>assessm.: all<br><50% hair loss,<br>Nurses<br>assessm.: all<br><25% hair loss) | Not stated<br>(>50% of<br>patients did not<br>report any side<br>effects.) | Cold sensation (n=6)<br>Other (n=9) | | Schaffrin-Nabe et al.,<br>2016<br>Gemeinschaftspraxis<br>Bochum, Germany | Non randomized<br>prospective | Neo-adjuvant EC-PT | Neo-adjuvant<br>EC-PT | Breast cancer<br>patients (n=40)<br>Scalp cooled (n=32),<br>controls (n=8) | Not stated | Hair-mass- index<br>(trichometer)<br>No visible hair loss<br>was considered<br>treatment success. | 100% (32/32) | 63% (20/32)<br>(no visible hair<br>loss)<br>Complete hair<br>loss in controls. | Not stated. | N/A | | Traub et al., 2016<br>Agaplesion Markus<br>Krankenhaus Frankfurt<br>am Main, Germany | Non randomized<br>prospective<br>October 2015 - | 4 × EC → 12 × PT (n = 7)<br>4 × PT → 4 × EC (n = 1)<br>4 × EC (n = 1)<br>18 × PT Mono (n = 1)<br>4 × Nab-PT Mono (n = 1)<br>18 × PT plus Myocet (n = 1) | N/A | Women with breast<br>cancer (n=12) | Not stated | Objective<br>assessment of<br>photographs. | 75% (9/12) | 75% (9/12)<br>(<20% hair loss) | Cooling-<br>induced side<br>effects | Hair loss (n=1),<br>or cooling-induced<br>side effects (n=2) | | Campennì et al., 2016<br>European Institute<br>Oncology, Milan | Non randomized<br>prospective | EC<br>EC-TX +/- Trastuzumab<br>TC | N/A | Patients with stage I-<br>III breast cancer<br>receiving adjuvant<br>chemotherapy<br>(n=109). | Not stated | Hair loss<br>Patient self-<br>assessment &<br>assessment by<br>treating physician<br>Dean scale | 79% (86/109) | 77% (84/109) | Headaches and<br>coldness.<br>No serious<br>adverse events. | Hair loss (n=12),<br>Discomfort during the<br>cooling period (n=4),<br>other reasons (n=7). | {8}------------------------------------------------ {9}------------------------------------------------ K170871 510(k) Notification DigniCap® Scalp Cooling System Page 7 of 15 | Publication<br>(author, year,<br>institution) | Type of study<br>(RCT, retrospective,<br>single arm<br>prospective<br>nonrandomized<br>studies.) | Treatment group | Control group | Sample size | Length of<br>Follow- up | Follow-up schedule | Completed Cooling<br>% | % Success with<br><50% hair loss | List of Adverse<br>Events | Reason for<br>discontinuation<br>of cooling | |---------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------|-----------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------|---------------------------------------------------------------------------------------------------------------------------------------|------------------------|------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------| | Schaffrin-Nabe et al.,<br>2015<br>Gemeinschafts praxis<br>für Hämatologie und<br>Onkologie Bochum,<br>Germany | Non randomized<br>prospective | E 90 mg/m² + C 3w→PT w<br>E 90 mg/m² + C 2w→ PT w<br>E 90 mg/m2 + C 3w ->DT 100<br>mg/m²<br>F + E 100 mg/m² + C<br>F + E 90 mg/m² + C<br>DT 75 mg/m² Carboplatin<br>AUC6<br>F + E 100 mg/m² + C → DT<br>100 mg/m²<br>E 150 mg/m² + PT 225<br>mg/m² + C 2000 mg/m²<br>DT 75 mg/m² + A50 C 500<br>mg/m² PT 100 mg/m² +<br>Carboplatin AUC2<br>Gemcitabine 1000 mg/m² +<br>Carboplatin AUC2<br>DT 75 mg/m2 + C 600 mg/m2 | N/A | In total 226 cancer<br>patients with solid<br>tumors.<br>Breast cancer<br>receiving (neo)<br>adjuvant and<br>palliative<br>chemotherapy<br>(n=136). | Not stated | Hair loss, common<br>toxicity criteria (CTC<br>German version 1.0)<br>scale for alopecia.<br>No or not visible hair<br>loss, CTC 0-1. | 3.1% (7/226) | 65%<br>(no or not<br>visible hair loss,<br>CTC 0-1.) | Slight and well<br>tolerable<br>sensation of<br>cold and mild<br>cranial<br>pressure. No<br>skin irritations<br>recorded. | Cold intolerance and<br>aversion. | | Andrews et al., 2014<br>Patricia Ritchie Centre,<br>the Mater Hospital<br>Sydney, Australia | Prospective feasibility | AC or combination<br>FEC or FEC-D<br>TC<br>Other | N/A | Early stage breast<br>cancer (n=122) | Not stated | Completion rate<br>Hair loss: Dean score | 80.5% (98/122) | 50% (61/122) | Not stated | Adverse events not<br>listed specifically for<br>patients using the<br>DigniCap. | {10}------------------------------------------------ K170871 510(k) Notification DigniCap® Scalp Cooling System Page 8 of 15 | Publication<br>(author, year,<br>institution) | Type of study<br>(RCT, retrospective,<br>single arm<br>prospective<br>nonrandomized<br>studies.) | Treatment group | Control group | Sample size | Length of<br>Follow- up | Follow-up schedule | Completed Cooling<br>% | % Success with<br><50% hair loss | List of Adverse<br>Events | Reason for<br>discontinuation<br>of cooling | |-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------| | Friedrich and<br>Carstensen, 2014<br>Mammazentrum,<br>Jerusalem Hospital,<br>Hamburg, Germany | Non randomized<br>prospective<br>June 2011-December<br>2012 | Multiple combinations<br>(Neo-) adjuvant<br>chemotherapy<br>E 90 mg/m² + C 600 mg/m²<br>(q3w*4) → DT 100/175<br>mg/m² (q3w*4)<br>F 500 mg/m2 + E 100 mg/m²<br>+ C 500 mg/m² (q3w*6)<br>F 500 mg/m2 + E 100 mg/m²<br>+ C 500 mg/m² (q3w*6) →<br>DT 100 mg/m2 (q3w*3)<br>E 90 mg/m² + C 600 mg/m²<br>(q3w*4)<br>CarboplaPt/DT (q3w*6)<br>Palliative chemotherapy<br>Taxol 135/Herceptin 8mg/kg<br>Halaven 1.23<br>Taxol 90 Avastin 10mg/kg<br>Carboplatin<br>Gemcitabine/Cisplatin | N/A | Breast cancer<br>(n=83)<br>Adjuvant (n=58)<br>Palliative (n=6)<br>Drop outs (n=19) | Not stated | Hair loss: Photo<br>documentation<br>Numerical VAS (1-<br>10) | 77%<br>(64/83 finished<br>chemotherapy and<br>scalp cooling.) | 52.6% | Feeling of cold<br>Headaches<br>Heaviness of<br>head<br>Scalp pain<br>Frequency<br>differed<br>between<br>patients with<br>(neo-) adjuvant<br>and palliative<br>CT | Out of 19 patients;<br>hair loss (n=5),<br>Cancer related<br>emergency cases or<br>disease progression<br>(n=3),<br>Feeling of<br>cold/headaches (n=2),<br>Unspecified<br>intolerance (n=9). | | Publication<br>(author, year,<br>institution) | Type of study<br>(RCT, retrospective,<br>single arm<br>prospective<br>nonrandomized<br>studies.) | Treatment group | Control group | Sample size | Length of<br>Follow- up | Follow-up schedule | Completed Cooling<br>% | % Success with<br><50% hair loss | List of Adverse<br>Events | Reason for<br>discontinuation<br>of cooling | | Udrea et al., 2014<br>Medisprof Oncology day<br>hospital, Cluj, Romania | Non randomized<br>prospective<br>March 2012 -<br>November 2013 | E 100mg/m2 + C 600 mg/m2<br>(n=53)<br>DT 100 mg/m² (n=10)<br>PT 175 mg/m² + carboplatin<br>AUC5-6 (n=21)<br>Irinotecan 80 mg/m2 (n=4),<br>Etoposide 100 mg/m² day 1-<br>3 + Carboplatin AUC5 (n=3)<br>TXT 75 mg/m² (n=2)<br>DT 75 mg/m² + Cisplatine 75<br>mg/m² + Capecitabine 1000<br>mg/m² (n=2)<br>Other combinations (n=13) | N/A | 108 cancer patients<br>(Treatment ongoing<br>for 8 patients). | Not stated | Hair loss: US NCI<br>(CTCAE) v4.0.<br>No alopecia / crown<br>like alopecia | 96% (104/108) | 57% (62/108)<br>(No alopecia /<br>crown like<br>alopecia) | Not stated | Discomfort (n=4) | | Meunier et al., 2013<br>1) Service de<br>chimiothérapie, Clinique<br>Charcot, Lyon, France<br>2) Centre Alexis Vautrin,<br>Nancy, France<br>3) Jerusalem<br>Krankenhaus<br>Mammazentrum<br>Hamburg, Germany | Non randomized<br>prospective<br>multicenter | (Neo-) adjuvant<br>chemotherapy<br>4 E90 C600 + 4 Taxotere<br>(n=26)<br>3 FEC100 + 3 Taxotere (n=10)<br>6 FEC 100 (n=15)<br>4 T75C600 +/- Trastuzumab<br>(n=7)<br>Taxane +/-anthracyclines<br>(n=11)<br>Palliative chemotherapy<br>Paclitaxel, Eribuline, Carbo +<br>cisplatin, gemcitabine (n=6) | N/A<br>(Comparison 3<br>versus 8<br>degrees C) | Cancer patients<br>(total n=133).<br>Breast cancer<br>(n=75)<br>(Neo) adjuvant<br>(n=69)<br>Palliative (n=6). | Not stated | Hair loss: Patient<br>self- assessment<br>VAS 0-100, with 100<br>being total hair<br>preservation.<br>(success: keeping<br>60-100% of hair) | 44.6% | (neo) adjuvant:<br>65%<br>Palliative: 83% | Headaches<br>(22%)<br>Cold sensation<br>or pain to the<br>scalp (4%) | Intolerance (9%)<br>Headaches (9%)<br>Unknown (9%)<br>Hair loss (22%)<br>Stopped<br>chemo/disease<br>progression (9%) | | Publication<br>(author, year,<br>institution) | Type of study<br>(RCT, retrospective,<br>single arm<br>prospective<br>nonrandomized<br>studies.) | Treatment group | Control group | Sample size | Length of<br>Follow- up | Follow-up schedule | Completed Cooling<br>% | % Success with<br><50% hair loss | List of Adverse<br>Events | Reason for<br>discontinuation<br>of cooling | | Ekwall et al., 2013<br>Örebro University<br>Hospital,<br>Örebro, Sweden | Randomized<br>prospective | PT (175 mg/m2) +<br>carboplatin (AUC 5-6) | N/A | Gynecological<br>cancer (total n=43);<br>Ovarian cancer<br>(n=22)<br>Endometrial cancer<br>(n=17)<br>Cervical cancer<br>(n=2)<br>Tubal cancer (n=1)<br>Peritoneal cancer<br>(n=1) | Not stated | Hair loss: Photo<br>documentation as<br>assessed by two<br>Investigators<br>VAS (0-10) as<br>assessed by the<br>patients | 91% (43/47) | 51% | Scalp cooling<br>was generally<br>very well<br>tolerated.<br>Headaches<br>VAS ≤ 1<br>Coldness<br>VAS ≤ 3.4 | Anaphylactic reactions,<br>peripheral neuropathy<br>and regimen<br>modification. | | Abramov et al., 2011<br>N.N. Blokhin Russian<br>Center Research,<br>Chemo- therapy and<br>combined treatment<br>Moscow. Russian<br>federation | Non randomized<br>prospective | ANR (n=5)<br>TX (n=8)<br>ANR+TX (n=7) | N/A | Breast cancer<br>(n=20) | Not stated | Hair loss: CTCAE<br>v3.0 Grade 1:<br>(thinning or patchy) | Not stated. | 100%<br>ANR: 100% no<br>hair loss<br>TX: 50% no hair<br>loss, 50% grade<br>1<br>ANR+TX: 29%<br>no hair loss,<br>71% Grade 1 | Not stated | N/A | | Kato et al., 2011<br>Kato Breast Clinic, Shiga,<br>Japan | Non randomized<br>prospective<br>August 2007- October<br>2010 | PT 60 mg/m2 weekly + C 400<br>mg/m2 (n=252)<br>PT+ H (n=29)<br>E 40 mg/m2 biweekly+ C 400<br>mg/m2 (n=54)<br>Other combinations (n=24)<br>(Combination by 5FU, CPT-<br>11, Gemcitabine and<br>CBDCA.) | N/A | Breast cancer<br>(n=359) | Not stated | Modified WHO scale<br>(Grade 1-5)<br>Success defined as<br><30% hair loss.<br>Photos | Not stated | 96% | No abnormal<br>scalp sensation<br>or headaches<br>during or after<br>treatment.<br>No scalp<br>metastasis. | N/A | | Byahov et al., 2006<br>Semashko Central<br>Clinical Hospital,<br>Moscow, Russia | Non randomized<br>prospective | ANR (n=43)<br>Non-ANR (n=34) | N/A | Breast cancer,<br>ovarian cancer,<br>colorectal cancer<br>(total n=77) | Not stated | Hair loss CTCAE v 3.0 | Not stated | ANR: 79%<br>Non-ANR: 94% | Well tolerated<br>by all patients. | N/A | | Publication<br>(author, year,<br>institution) | Type of study<br>(RCT,<br>retrospective,<br>single arm<br>prospective<br>nonrandomized<br>studies.) | Treatment group | Control<br>group | Sample size | Length of<br>Follow- up | Follow-up<br>schedule | Completed<br>Cooling % | % Success<br>with<br><50% hair<br>loss | List of<br>Adverse<br>Events | Reason for<br>discontinuation<br>of cooling | | Ridderheim et al.,<br>2003<br>Lund University<br>Hospital, Sweden | Non randomized<br>prospective pilot | PT 175 mg/m²,<br>Carboplatin AUC 5<br>PT 175 mg/m², E 75<br>mg/m2, Carboplatin AUC<br>ട<br>DT 100 mg/m²<br>PT 175 mg/m²<br>Gemcitabine 1,000<br>mg/m² day 1+8, E 75<br>mg/m² day 1<br>E 60 mg/m², C 600<br>mg/m², 5-FU 600 mg/m²<br>D 50 mg/m², Cisplatin 50<br>mg/m²<br>E 50 mg/m², Carboplatin<br>AUC 5<br>Vinorelbine 30 mg/m²<br>D 25 mg/m²<br>Bleomycin 10,000 E/m²<br>Vinblastin 6 mg/m²<br>Darcabazin 375 mg/m²<br>Bleomycin 30,000 day 1,<br>5, 16<br>Etoposide 100 mg/m²<br>day 1-5<br>Cisplatin 20 mg/m² day<br>1—5<br>Topotecan 1.0 mg/m²<br>day 1-5<br>Etoposide 50 mg/day 6-<br>12<br>Topotecan 1.0 mg/m² | | In total 74 cancer<br>patients<br>Ovarian cancer<br>(n=60)<br>Hodgkin´s<br>Lymphoma (n=8)<br>Breast cancer<br>(n=3)<br>Endometrial<br>cancer (n=2)<br>Sarcoma (n=1) | 15 months<br>(range 3-44). | Hair loss:<br>Photo<br>documentation<br>Numerical VAS<br>(0-10) | 97% (72/74) | Minimal to<br>no hair loss in<br>ANR or TX<br>treated<br>patients.<br>Median hair<br>loss was VAS<br>6 (range 1.5-<br>8) in patients<br>treated when<br>combining<br>ANR and TX. | Discomfort<br>was modest<br>(median<br>value 1.5;<br>range 0.5-8).<br>No presence<br>of scalp<br>metastases | Discomfort | | Publication<br>(author, year,<br>institution) | Type of study<br>(RCT,<br>retrospective,<br>single arm<br>prospective<br>nonrandomized<br>studies.) | Treatment group | Control<br>group | Sample size | Length of<br>Follow- up | Follow-up<br>schedule | Completed<br>Cooling % | % Success<br>with<br><50% hair<br>loss | List of<br>Adverse<br>Events | Reason for<br>discontinuation<br>of cooling | | Henriksen et al.,<br>2003<br>Herlev Hospital,<br>University of<br>Copenhagen<br>Denmark | Non randomized<br>prospective interim | Seven cycles of FEC<br>(Adjuvant). Dose not<br>stated. | N/A | Breast cancer<br>(n=26) | Not stated | Hair loss:<br>Patients self-<br>assessment<br>Clinical photos<br>Numerical VAS,<br>wig use<br>Side effects:<br>Numerical VAS<br>Post-treatment<br>questionnaire | Not stated | 88% success<br>rate,<br>23/26<br>patients<br>choose not to<br>use a wig. | Side effects<br>and extra<br>time<br>accepted by<br>the patients. | N/A | | Lundgren et al., 1999<br>Umeå University<br>Hospital & Lund<br>University Hospital,<br>Sweden | Non randomized<br>prospective pilot | PT 135-175 mg/m2 (n=3)<br>DT 100 mg/ m2 (n=3)<br>FEC (n=2)<br>CMF (n=1) | PT | Ovarian cancer<br>(n=3)<br>Breast cancer<br>(n=6)<br>Ovarian cancer<br>control (n=2) | Not stated | Hair loss:<br>Numerical VAS (1-<br>10) assessed by<br>independent<br>observers.<br>Discomfort<br>assessed by the<br>patients. | 100% | Scalp cooled<br>patients:<br>100%<br>Controls: 0%<br>(Minimal to<br>no hair loss<br>(VAS < 2.5) in<br>all scalp<br>cooled<br>patients.) | Discomfort<br>level initially<br>low (mean<br>VAS 3) and<br>decreased<br>after 10 min<br>(mean VAS<br>1.5).<br>No presence<br>of scalp<br>metastases | N/A | {11}------------------------------------------------ {12}------------------------------------------------ K170871 510(k) Notification DigniCap® Scalp Cooling System Page 10 of 15 {13}------------------------------------------------ {14}------------------------------------------------ # K170871 510(k) Notification DigniCap® Scalp Cooling System Page 12 of 15 DigniCap® Scalp Cooling System {15}------------------------------------------------ K170871 510(k) Notification DigniCap® Scalp Cooling System Page 13 of 15 #### Chemotherapy and Abbreviations ANR: anthracyclines H: Herceptin TCH: docetaxel + carboplatin + trastuzumab AC: doxorubin + cyclophosphamide M: methotrexate TC: docetaxel + cyclophosphamide C: cyclophosphamide D: doxorubicin DT: docetaxel E: epirubicin F: 5-fluorouracil Mi: mitoxanthrone PT: paclitaxel TX: taxanes Vc: vincristine {16}------------------------------------------------ #### Bibliography: - 1. 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Ekwall, E, et al."Determinationofthemosteffectivecoolingtemperaturefortheprevention of chemotherapy-inducedalopecia." Molecular and Clinical Oncology. Vol. 1. 2013. 1071. - 8. Meunier,A,etal."Evaluationdelatoléranceetdel'efficacitéd'uncasqueàrefrigeration continue (DIGNICAP)danslapréventiondel'alopéciechimio-induite."(Translationfrom French). Presented at the Society For Science-Based Medicine , 2013. - 9. Udrea.A. "Scalpcoolingsystemingchemotherapy-induced alopecia: a pilot study on 108 patients -a Romanian oncology -dayhospitalexperience."Medisprof Oncology. Psycho-Oncology 23 (Suppl. 3):169-254 (2014), P1-0062. - 10. Friedrichs,KandMCarstensen. "Successfulreductionofalopeciainducedbyanthracycline and taxane containing adjuvant chemotherapy in breast cancer -clinical evaluation of sensorcontrolledscalpcooling."SPrignerPlus. Vol. 3, No. 500 2014. 1-7. - 11. Andrews.K.etal. "CrowningGlory:Isthatthewholestory?Implementingscalpcoolingin an Australian setting." 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Campenni,GM,etal."Preventingchemotherapy-induced alopecia by scalp cooling: preliminary data from a study on the efficacy and safety of dignicap® system in breast cancer patients."Ann Oncol. Vol. 27. Supp. 4. 2016. iv63-iv64. - 17. Fehr,MK,etal. "Sensor-controlled scalp cooling to prevent chemotherapy-induced alopecia in {17}------------------------------------------------ K170871 510(k) Notification DigniCap® Scalp Cooling System Page 15 of 15 femalecancerpatients."Current Oncology. Vol. 23, No. 6. December 2016. e576-e582. - 18. Hernández R.E. et al., Experience at the ABC Medical Center of Mexico City, 2010-2015, using the scalp cooling system DigniCap® for the prevention of chemotherapy-induced alopecia. Poster 850794 at the San Antonio Breast…