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The Desmoid Tumor Research Foundation

June 2018

Phase I trial of z-endoxifen with estrogen receptor imaging in adults with advanced hormone receptor-positive solid tumors including desmoid and gynecologic tumors

Author Information

N Takebe, G O'Sullivan Coyne, S Kummar, J Reid, R Piekarz, L Harris, L Juwara, M Flanagan Quinn, N Moore, P Choyke, E Mena, L Lindenberg, F Lin, M Goetz, R McGovern, H Streicher, J Covey, J Collins, J Doroshow, A Chen

NCI/ NIH, Elkridge, MD; Early Clinical Triials Development Program, DCTD, NCI at the NIH, Bethesda, MD; Division of Cancer Treatment & Diagnosis, NCI, Bethesda, MD; Dept of Oncology, Mayo Clinic, Rochester, MN; Cancer Therapy Evaluation Program, NCI, Bethesda, MD; Cancer Diagnosis Program, NCI, Rockville, MD; NCI at Frederick, Bethesda, MD, US; National Naval Medical Center, Rockville, MD; DCTD, NCI, NIH, Bethesda, MD; NCI at the NIH, Bethesda, MD; Molecular Imaging Program, Center for Cancer Research, NCI at the NIH, Bethesda, MD; NIH, Washington, DC; NIH, NCI, Bethesda, MD; Mayo Clinic, Rochester, MN; Division of Cancer Treatment and Diagnosis, NCI, NIH, Bethesda, MD; NCIl, Cancer Institute/Division of Cancer Treatment & Diagnosis, Rockville, MD; Center for Cancer Research, Division of Cancer Treatment and Diagnosis, Bethesda, MD

Publication

J Clin Onc

Summary

Differential response to tamoxifen observed in patients (pts) with hormone receptor-positive cancer may be due to variations in tamoxifen metabolism from CYP2D6 genetic polymorphisms that limit exposure to the active metabolite, z-endoxifen (Z). We conducted a phase 1 clinical trial (3+3 design) with estrogen receptor imaging to determine the safety, MTD, and pharmacokinetics (PK) of oral Z. Adults with refractory gynecologic tumors, hormone-positive breast or other solid tumors, or desmoid tumors were eligible with ECOG performance status of 0-2 and adequate organ functions. Z was administered at 20, 40, 60, 100, 140, 200, 280, and 360 mg q day on a 28-day cycle. Estrogen receptor imaging with 16 alpha-[18F]-fluoro-17 beta-estradiol (FES)-PET was performed before dosing and, if positive, repeated during C1W1. We established a targeted maximum dose of 360 mg/day Z and evidence of antitumor activity was observed. Oral Z administration produces Z plasma exposures well above those obtained after therapeutic doses of tamoxifen.

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