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Nci 2017-09-01 Phase I Trial of Endoxifen Gel Versus NWU2017-09-01 Protocol Version 6.5, May 11, 2020 COVER PAGE DCP Protocol #: NWU2017-09-01 Local Protocol #: NCI 2017-09-01 PHASE I TRIAL OF ENDOXIFEN GEL VERSUS PLACEBO GEL IN WOMEN UNDERGOING BREAST SURGERY Consortium Name: Northwestern Cancer Prevention Consortium Organization Name: Northwestern University Name of Consortium Principal Seema A. Khan, M.D. Investigator: 303 E. Superior, Suite 4-111 Chicago, IL 60611 Tel: (312) 503-4236 Fax: (312) 503-2555 E-mail: [email protected] Organization Name: Northwestern University Protocol Principal Seema A. Khan, M.D. Investigator and Protocol Chair: Professor of Surgery 303 E. Superior, Suite 4-111 Chicago, IL 60611 Tel: (312) 503-4236 Fax: (312) 503-2555 E-mail: [email protected] Organization: Memorial Sloan-Kettering Cancer Center Investigator: Melissa Pilewskie, M.D. Evelyn H. Lauder Breast Center 300 East 66th Street New York, NY 10065 Tel: 646-888-4590 Fax: 646-888-4921 E-mail: [email protected] Organization: Cedars-Sinai Medical Center Investigator: Scott Karlan, M.D. Saul and Joyce Brandman Breast Center in the Samuel Oschin Cancer Center 310 N. San Vicente Blvd., Room 314 West Hollywood, CA 90048-1810 Tel: (310) 423-9331 Fax: (310) 423-9339 E-mail: [email protected] Organization: Northwestern University Statistician: Masha Kocherginsky, Ph.D. 680 N. Lake Shore Dr., Suite 1400 –1– NWU2017-09-01 Protocol Version 6.5, May 11, 2020 Chicago, IL 60611 Telephone: (312) 503- 4224 Fax: (312) 908- 9588 Email: [email protected] IND Sponsor: NCI/Division of Cancer Prevention IND# Agent(s)/Supplier: National Cancer Institute NCI Contract # HHSN2612201200035I Protocol Template: Version 8.5 08/31/2016 Protocol Version Date: May 11, 2020 Protocol Revision or Amendment # Version 6.5 –2– NWU2017-09-01 Protocol Version 6.5, May 11, 2020 SCHEMA NWU2017-09-01: Phase I trial of endoxifen gel versus placebo gel in women undergoing breast surgery Women scheduled for mastectomy1 Screening Visit 1 – consent, baseline tests, BESS Q, skin photos 2:1 Randomization in Cohorts 1 and 2. All subjects in Cohort 3 will receive active agent without randomization. A maximum of 38 subjects will be enrolled. Cohort 12: 10mg daily3 Endoxifen gel (8) vs. placebo gel (4) Cohort 2: 20mg daily4 Endoxifen gel (8) vs. placebo gel (4) Cohort 3: 10mg5 Endoxifen gel (8) Daily treatments to both breasts for 21-28 days6 Weekly phone calls for compliance and AE assessment Study Visit 1: End of study treatment tests, BESS Q, skin photos Study Visit 2: Mastectomy procedure Study Visit 3: 7-14 day post-op visit Final phone call/email/text message at 60 days Endpoints 1) Skin toxicity evaluation using CTCAE v 4 2) Drug concentration in breast tissue and blood 3) Breast tissue biomarkers of endoxifen effect 4) Coagulation proteins measures of systemic estrogenicity in plasma 5) Future studies of drug metabolism genes in germline DNA from peripheral blood (Buffy Coat) for DNA/RNA isolation (optional) 1: Mastectomy for stage 0-III breast cancer therapy or prophylaxis (BRCA mutation carriers, women with strong family history or lobular carcinoma in situ or other conditions where prophylactic mastectomy has been elected) 2: If more than one subject experiences dose-limiting toxicity in Cohort 1, the cohort will be extended to include an additional 6 subjects: 10mg daily3 Endoxifen gel (4) vs. placebo gel (2). 3: 10 mg daily, applied 5 mg per breast 4: 20 mg daily, applied 10 mg per breast 5: Although no more than one subject experienced dose-limiting toxicity in Cohort 2, interim analysis showed more skin irritation and no permeation advantage with higher dose. Therefore, 10 mg daily dosage will be used for Cohort 3. 6: All subjects will undergo mastectomy at 21-28 days. If surgery needs to be delayed, an additional 7 days of treatment is allowed. –3– NWU2017-09-01 Protocol Version 6.5, May 11, 2020 TABLE OF CONTENTS COVER PAGE.............................................................................................................................................. 1 SCHEMA ...................................................................................................................................................... 3 1. OBJECTIVES ..................................................................................................................................... 6 1.1 Primary Objective ........................................................................................................................................ 6 1.2 Secondary Objectives .................................................................................................................................. 6 2. BACKGROUND................................................................................................................................. 6 2.1 Need for new approaches for women with duct carcinoma in situ and those at high risk ........................... 6 2.2 Endoxifen ..................................................................................................................................................... 7 2.3 Rationale ...................................................................................................................................................... 9 3. SUMMARY OF STUDY PLAN ...................................................................................................... 10 4. PARTICIPANT SELECTION .......................................................................................................... 12 4.1 Inclusion Criteria ....................................................................................................................................... 12 4.2 Exclusion Criteria ...................................................................................................................................... 13 4.3 Inclusion of Women and Minorities .......................................................................................................... 14 4.4 Recruitment and Retention Plan ................................................................................................................ 14 5. AGENT ADMINISTRATION .......................................................................................................... 15 5.1 Dose Regimen and Dose Groups ............................................................................................................... 15 5.2 Study Agent Administration ...................................................................................................................... 16 5.3 Run-in Procedures ..................................................................................................................................... 16 5.4 Contraindications ....................................................................................................................................... 16 5.5 Concomitant Medications .......................................................................................................................... 16 5.6 Dose Modification ..................................................................................................................................... 17 5.7 Adherence/Compliance .............................................................................................................................. 17 6. PHARMACEUTICAL INFORMATION ......................................................................................... 17 6.1 Study Agent (IND , NCI, Division of Cancer Prevention) ............................................................ 17 6.2 Reported Adverse Events and Potential Risks ........................................................................................... 17 6.3 Availability ................................................................................................................................................ 20 6.4 Agent Distribution ..................................................................................................................................... 20 6.5 Agent Accountability ................................................................................................................................. 20 6.6 Packaging and Labeling ............................................................................................................................. 20 6.7 Storage ....................................................................................................................................................... 20 6.8 Registration/Randomization ...................................................................................................................... 21 6.9 Blinding and Unblinding Methods ............................................................................................................. 21 6.10 Agent Destruction/Disposal ....................................................................................................................... 22 7. CLINICAL EVALUATIONS AND PROCEDURES ...................................................................... 22 7.1 Schedule of Events .................................................................................................................................... 22 7.2 Baseline Testing/Pre-study Evaluation ...................................................................................................... 23 7.3 Evaluation During Study Intervention ....................................................................................................... 24 7.4 Evaluation
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