Robert A Burger1, Wei Deng2, Vicky Makker3, Yvonne Collins4, Heidi Gray5, Robert Debernardo6, Lainie P Martin7, Carol Aghajanian8. 1. Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, PA 19104, United States of America. Electronic address: robert.burger@uphs.upenn.edu. 2. NRG Oncology, Clinical Trial Development Division, Biostatistics & Bioinformatics, Roswell Park, Buffalo, NY 14263, United States of America. Electronic address: wdeng@gogstats.org. 3. Department of Medicine, Memorial Sloan Kettering Cancer, New York, NY 10065, United States of America. Electronic address: makkerv@mskcc.org. 4. Department of Obstetrics & Gynecology, University of Illinois at Chicago CCOP, Chicago, IL 60612, United States of America. Electronic address: yvonne.collins-md@advocatehealth.com. 5. Dept. of OB/GYN, Washington University School of Medicine, Seattle, WA 98195, United States of America. Electronic address: hgray@u.washington.edu. 6. Department of Obstetrics & Gynecology, Case Western University Hospital, Cleveland, OH 44106, United States of America. Electronic address: debernr@ccf.org. 7. Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA 19111, United States of America. Electronic address: lainie.martin@fccc.edu. 8. Department of Medicine, Memorial Sloan Kettering Cancer, New York, NY 10065, United States of America. Electronic address: aghajanc@MSKCC.ORG.
Abstract
OBJECTIVE: To determine the efficacy of dalantercept, a soluble ALK1 inhibitor receptor fusion protein, in patients with persistent or recurrent ovarian carcinoma and related malignancies. METHODS: Eligibility criteria included measurable disease, 1-2 prior cytotoxic regimens and GOG performance status (PS) ≤2. Dalantercept was administered subcutaneously at 1.2 mg/kg every 3 weeks until disease progression or development of unacceptable toxicity. The primary null hypothesis was the probability of response ≤0.10 and the probability of 6-month progression-free survival without receipt of non-protocol therapy (event-free survival at 6 months, EFS6) ≤0.15, using RECIST 1.1 criteria. RESULTS: The first stage was closed after enrollment of 30 participants with median age of 56.5 years, high-grade serous histology in 76.7%, 2 prior regimens in 46.7%, and platinum-free interval <6 months in 73.3%. All participants discontinued dalantercept, 24 (80.0%), 5 (16.7%) and 1 (3.3%) due to progression, toxicity, and other reason, respectively. The median number of treatment cycles per patient was 2 (range 1-29). There were six treatment-related grade 3 AEs and no grade ≥4 AEs. There were no objective responses. EFS6 was reached in 20% (6 out of 30 participants, 90% CI 9.1% to 35.7%). CONCLUSIONS: Though safe, dalantercept as administered had limited efficacy in this patient population overall.
OBJECTIVE: To determine the efficacy of dalantercept, a soluble ALK1 inhibitor receptor fusion protein, in patients with persistent or recurrent ovarian carcinoma and related malignancies. METHODS: Eligibility criteria included measurable disease, 1-2 prior cytotoxic regimens and GOG performance status (PS) ≤2. Dalantercept was administered subcutaneously at 1.2 mg/kg every 3 weeks until disease progression or development of unacceptable toxicity. The primary null hypothesis was the probability of response ≤0.10 and the probability of 6-month progression-free survival without receipt of non-protocol therapy (event-free survival at 6 months, EFS6) ≤0.15, using RECIST 1.1 criteria. RESULTS: The first stage was closed after enrollment of 30 participants with median age of 56.5 years, high-grade serous histology in 76.7%, 2 prior regimens in 46.7%, and platinum-free interval <6 months in 73.3%. All participants discontinued dalantercept, 24 (80.0%), 5 (16.7%) and 1 (3.3%) due to progression, toxicity, and other reason, respectively. The median number of treatment cycles per patient was 2 (range 1-29). There were six treatment-related grade 3 AEs and no grade ≥4 AEs. There were no objective responses. EFS6 was reached in 20% (6 out of 30 participants, 90% CI 9.1% to 35.7%). CONCLUSIONS: Though safe, dalantercept as administered had limited efficacy in this patient population overall.
Authors: Kian Behbakht; Michael W Sill; Kathleen M Darcy; Stephen C Rubin; Robert S Mannel; Steven Waggoner; Russell J Schilder; Kathy Q Cai; Andrew K Godwin; R Katherine Alpaugh Journal: Gynecol Oncol Date: 2011-07-12 Impact factor: 5.482
Authors: Lydia Usha; Michael W Sill; Kathleen M Darcy; Doris M Benbrook; Jean A Hurteau; David P Michelin; Robert S Mannel; Parviz Hanjani; Koen De Geest; Andrew K Godwin Journal: Gynecol Oncol Date: 2011-03-17 Impact factor: 5.482
Authors: Thomas F Rocereto; William E Brady; Mark S Shahin; James S Hoffman; Laurie Small; Jacob Rotmensch; Robert S Mannel Journal: Gynecol Oncol Date: 2009-11-17 Impact factor: 5.482
Authors: Robert A Burger; Michael W Sill; Bradley J Monk; Benjamin E Greer; Joel I Sorosky Journal: J Clin Oncol Date: 2007-11-20 Impact factor: 44.544
Authors: Dianne Mitchell; Eileen G Pobre; Aaron W Mulivor; Asya V Grinberg; Roselyne Castonguay; Travis E Monnell; Nicolas Solban; Jeffrey A Ucran; R Scott Pearsall; Kathryn W Underwood; Jasbir Seehra; Ravindra Kumar Journal: Mol Cancer Ther Date: 2010-02-02 Impact factor: 6.261
Authors: Martin H Voss; Rupal S Bhatt; Nicholas J Vogelzang; Mayer Fishman; Robert S Alter; Brian I Rini; J Thaddeus Beck; Monika Joshi; Ralph Hauke; Michael B Atkins; Earle Burgess; Theodore F Logan; David Shaffer; Rahul Parikh; Nauman Moazzam; Xiaosha Zhang; Chad Glasser; Matthew L Sherman; Elizabeth R Plimack Journal: Cancer Date: 2019-04-05 Impact factor: 6.860