Phase II evaluation of dalantercept, a soluble recombinant activin receptor-like kinase 1 (ALK1) receptor fusion protein, for the treatment of recurrent or persistent endometrial cancer: An NRG Oncology/Gynecologic Oncology Group Study 0229N

Autor: Vicky Makker, Virginia L. Filiaci, Katherine M. Moxley, Carol Aghajanian, Christopher J. Darus, Gregory P. Sutton, Lee-may Chen, James E. Kendrick
Rok vydání: 2015
Předmět:
Oncology
Dalantercept
Activin Receptors
Activin Receptors
Type II
Peripheral edema
Phases of clinical research
Prior Radiation Therapy
Cancer
Neovascularization
Pathologic
Obstetrics and Gynecology
Recurrent endometrial cancer
Hematology
Middle Aged
Bowel obstruction
Local
6.1 Pharmaceuticals
Female
medicine.symptom
Adult
medicine.medical_specialty
Recombinant Fusion Proteins
Oncology and Carcinogenesis
Gynecologic oncology
Type II
Disease-Free Survival
Article
Paediatrics and Reproductive Medicine
Rare Diseases
Uterine Cancer
Clinical Research
Internal medicine
medicine
Carcinoma
Humans
Oncology & Carcinogenesis
Adverse effect
Neovascularization
ALK-1
Aged
Pathologic
business.industry
Endometrial cancer
Evaluation of treatments and therapeutic interventions
medicine.disease
Endometrial Neoplasms
Immunoglobulin Fc Fragments
Neoplasm Recurrence
Neoplasm Recurrence
Local
business
Zdroj: Gynecologic oncology, vol 138, iss 1
ISSN: 0090-8258
DOI: 10.1016/j.ygyno.2015.04.006
Popis: Objective This two-stage phase II study assessed activity of single agent dalantercept in patients with recurrent/persistent endometrial carcinoma (EMC). Methods Eligible patients had persistent/recurrent EMC after 1–2 prior cytotoxic regimens, measurable disease (RECIST 1.1), and GOG performance≤2. Dalantercept 1.2mg/kg subcutaneous was administered once every 3weeks until disease progression (PD)/development of prohibitory toxicity. Primary objectives were to estimate the proportion of patients with persistent/recurrent EMC, who survive progression-free without receiving non-protocol therapy (TPFS) for at least 6months and to estimate the proportion having objective tumor response. Results All 28 enrolled patients were eligible and evaluable. Median age: 62years. Most common histologies: 32% Grade 1/2 endometrioid and 54% serous tumors. Prior treatment: 1 or 2 regimens in 82% and 18% of patients, respectively. Eighteen patients received prior radiation therapy. Patients received 1–12 cycles of dalantercept, and 46% of patients received ≤2cycles. The most common adverse events (AE) were fatigue, anemia, constipation and peripheral edema. Grade 3/4 AEs occurred in 39% and 4% of patients. One grade 5 gastric hemorrhage in a patient with a history of radiation fibrosis/small bowel obstruction was deemed possibly dalantercept-related. All patients are off study: 86% for PD. No ORs were observed; 57% had stable disease and 11% had TPFS>6 mos. Median progression-free and overall survival: 2.1months (90% CI: 1.4–3.2) and 14.5months (90% CI: 7.0–17.5), respectively. Conclusions Dalantercept has insufficient single agent activity in recurrent EMC to warrant further investigation at this dose level and schedule.
Databáze: OpenAIRE
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