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Ref Type Journal Article
PMID (29138343)
Authors Wahner Hendrickson AE, Menefee ME, Hartmann LC, Long HJ, Northfelt DW, Reid JM, Boakye-Agyeman F, Kayode O, Flatten KS, Harrell MI, Swisher EM, Poirer GG, Satele D, Allred J, Lensing JL, Chen A, Ji J, Zang Y, Erlichman C, Haluska P, Kaufmann SH
Title A Phase I Clinical Trial of the Poly(ADP-ribose) Polymerase Inhibitor Veliparib and Weekly Topotecan in Patients with Solid Tumors.
Journal Clinical cancer research : an official journal of the American Association for Cancer Research
Vol 24
Issue 4
Date 2018 02 15
URL
Abstract Text Purpose: To determine the dose limiting toxicities (DLT), maximum tolerated dose (MTD), and recommended phase II dose (RP2D) of veliparib in combination with weekly topotecan in patients with solid tumors. Correlative studies were included to assess the impact of topotecan and veliparib on poly(ADP-ribose) levels in peripheral blood mononuclear cells, serum pharmacokinetics of both agents, and potential association of germline repair gene mutations with outcome.Experimental Design: Eligible patients had metastatic nonhematologic malignancies with measurable disease. Using a 3 + 3 design, patients were treated with veliparib orally twice daily on days 1-3, 8-10, and 15-17 and topotecan intravenously on days 2, 9, and 16 every 28 days. Tumor responses were assessed by RECIST.Results: Of 58 patients enrolled, 51 were evaluable for the primary endpoint. The MTD and RP2D was veliparib 300 mg twice daily on days 1-3, 8-10, and 15-17 along with topotecan 3 mg/m2 on days 2, 9, and 16 of a 28-day cycle. DLTs were grade 4 neutropenia lasting >5 days. The median number of cycles was 2 (1-26). The objective response rate was 10%, with 1 complete and 4 partial responses. Twenty-two patients (42%) had stable disease ranging from 4 to 26 cycles. Patients with germline BRCA1, BRCA2, or RAD51D mutations remained on study longer than those without homologous recombination repair (HRR) gene mutations (median 4 vs. 2 cycles).Conclusions: Weekly topotecan in combination with veliparib has a manageable safety profile and appears to warrant further investigation. Clin Cancer Res; 24(4); 744-52. ©2017 AACR.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
Unknown unknown ovarian carcinoma not applicable Topotecan + Veliparib Phase I Actionable In a Phase I trial, the combination of Veliparib (ABT-888) and topotecan demonstrated safety and tolerability, and resulted in an objective response rate of 9% (4/45; 1 complete response and 3 partial responses) and stable disease in 21 patients with ovarian carcinoma (PMID: 29138343; NCT01012817). 29138343
Unknown unknown Advanced Solid Tumor not applicable Topotecan + Veliparib Phase I Actionable In a Phase I trial, the combination of Veliparib (ABT-888) and topotecan demonstrated safety and tolerability, and resulted in an objective response rate of 10% (5/51; 1 complete response and 4 partial responses) and stable disease for at least 4 months in 43% (22/51) of patients with advanced solid tumors, with the majority of the patients having ovarian, fallopian tube, or primary peritoneal cancer (PMID: 29138343; NCT01012817). 29138343