Carboplatin, Paclitaxel, Bevacizumab, and Veliparib in Treating Patients With Newly Diagnosed Stage II-IV Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cancer
A Phase I Study of Intravenous Carboplatin/Paclitaxel or Intravenous and Intraperitoneal Paclitaxel/Cisplatin in Combination With Continuous or Intermittent /CTEP-Supplied Agent ABT-888 (NSC #737664) and CTEP-Supplied Agent Bevacizumab (NSC #704865) in Newly Diagnosed Patients With Previously Untreated Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Cancer
5 other identifiers
interventional
431
1 country
23
Brief Summary
This phase I trial studies the side effects and best dose of veliparib when given together with carboplatin, paclitaxel, and bevacizumab in treating patients with newly diagnosed stage II-IV ovarian epithelial, fallopian tube, or primary peritoneal cancer. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cells to repair themselves from damage and survive. Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Bevacizumab, a type of drug called a monoclonal antibody, blocks tumor growth by targeting certain cells and preventing the growth of new blood vessels that tumors need to grow. Giving veliparib together with carboplatin, paclitaxel, and bevacizumab may kill more tumor cells.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Oct 2009
Longer than P75 for phase_1
23 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 2, 2009
CompletedFirst Posted
Study publicly available on registry
October 5, 2009
CompletedStudy Start
First participant enrolled
October 28, 2009
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 2, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
April 10, 2020
CompletedOctober 20, 2021
October 1, 2021
6.9 years
October 2, 2009
October 19, 2021
Conditions
Outcome Measures
Primary Outcomes (2)
Incidence of dose-limiting toxicities (DLTs) occurring in the first or second course of treatment (dose-escalation phase)
Up to day 42
Incidence of DLTs occurring in the first 4 courses of treatment (feasibility phase)
Up to day 84
Secondary Outcomes (3)
Objective tumor response (complete and partial response) as assessed by the Response Evaluation Criteria in Solid Tumors (RECIST)
Up to 11 years
Progression-free survival
Time from start of treatment to time of progression or death, assessed up to 11 years
Incidence of toxicity, graded according to National Cancer Institute CTCAE version 4.0
Up to 30 days after last dose of treatment
Other Outcomes (2)
Change in PARP inhibition in PBMCs
Day 1 to day 22 (day 1 of course 1 to day 1 of course 2)
Genomic BRCA mutation status
Baseline
Study Arms (3)
Regimen I (paclitaxel, carboplatin, bevacizumab, veliparib)
EXPERIMENTALPatients receive paclitaxel IV over 3 hours, carboplatin IV over 30 minutes, and bevacizumab IV over 30-90 minutes (beginning in course 2) on day 1. Patients also receive veliparib PO BID on days 1-21. Treatment repeats every 21 days for 6 courses. Patients then receive bevacizumab alone on day 1. Treatment with bevacizumab repeats every 21 days for 16 courses in the absence of disease progression or unacceptable toxicity.
Regimen II (paclitaxel, carboplatin, bevacizumab, veliparib)
EXPERIMENTALPatients receive paclitaxel IV over 1 hour on days 1, 8, and 15. Patients also receive carboplatin, bevacizumab, and veliparib as in Regimen I. Treatment repeats every 21 days for 6 courses. Patients then receive bevacizumab alone on day 1. Treatment with bevacizumab repeats every 21 days for 16 courses in the absence of disease progression or unacceptable toxicity.
Regimen III (paclitaxel, cisplatin, bevacizumab, veliparib)
EXPERIMENTALPatients receive paclitaxel IV over 3 hours on day 1 and IP on day 8, and cisplatin IP on day 1 or 2. Patients also receive bevacizumab and veliparib as in Regimen I. Treatment repeats every 21 days for 6 courses. Patients then receive bevacizumab alone on day 1. Treatment repeats every 21 days for 16 courses in the absence of disease progression or unacceptable toxicity.
Interventions
Given IV
Given IV
Given IP
Correlative studies
Given IV or IP
Given PO
Eligibility Criteria
You may qualify if:
- Patients with a histologic diagnosis of epithelial ovarian, fallopian tube, or primary peritoneal carcinoma, or carcinosarcoma stage II, III, or IV with either optimal (=\< 1 cm residual disease) or suboptimal residual disease
- All patients must have a procedure for determining diagnosis of epithelial ovarian, fallopian tube, primary peritoneal, or carcinosarcoma with appropriate tissue for histologic evaluation
- Patients with the following histologic cell types are eligible:
- Serous adenocarcinoma, endometrioid adenocarcinoma, mucinous adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial adenocarcinoma, transitional cell carcinoma, malignant Brenner's tumor, adenocarcinoma not otherwise specified (N.O.S.) or carcinosarcoma
- Absolute neutrophil count (ANC) greater than or equal to 1,500/mm\^3, equivalent to CTEP Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, grade 1; this ANC cannot have been induced or supported by granulocyte colony stimulating factors
- Platelets greater than or equal to 100,000/mm\^3
- Regimens I and II: Creatinine =\< 1.5 x institutional upper limit normal (ULN), CTCAE grade 1
- Regimen III: Creatinine no greater than the institutional upper limits of normal
- Bilirubin less than or equal to 1.5 x ULN (CTEP CTCAE version 4.0, grade 1)
- Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase \[AST\]) less than or equal to 3 x ULN (CTEP CTCAE version 4.0, grade 1)
- Alkaline phosphatase less than or equal to 2.5 x ULN (CTEP CTCAE version 4.0, grade 1)
- Albumin greater than or equal to 3.0 g/dL
- Neuropathy (sensory and motor) less than or equal to CTEP CTCAE version 4.0, grade 1
- Prothrombin time (PT) such that international normalized ratio (INR) is =\< 1.5 x ULN (or an in-range INR, usually between 2 and 3, if a patient is on a stable dose of therapeutic warfarin) and a partial thromboplastin time (PTT) \< 1.5 x ULN
- Patients must have a Gynecologic Oncology Group (GOG) performance status of 0, 1, or 2
- +3 more criteria
You may not qualify if:
- Patients with a current diagnosis of borderline epithelial ovarian tumor (formerly "tumors of low malignant potential") or recurrent invasive epithelial ovarian, primary peritoneal or fallopian tube cancer treated with surgery only (such as patients with stage IA or IB low-grade epithelial ovarian or fallopian tube cancers) are not eligible
- NOTE: Patients with a prior diagnosis of a borderline tumor that was surgically resected and who subsequently develop an unrelated, new invasive epithelial ovarian, peritoneal primary or fallopian tube cancer are eligible, provided that they have not received prior chemotherapy for any ovarian tumor
- Patients with synchronous primary endometrial cancer or a past history of endometrial cancer, unless all of the following conditions are met:
- Stage not greater than IB
- No more than superficial myometrial invasion
- No vascular or lymphatic invasion
- No poorly differentiated subtypes, including papillary serous, clear cell, or other International Federation of Gynecology and Obstetrics (FIGO) grade 3 lesions
- Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancer and other specific malignancies as noted, are excluded if there is any evidence of other malignancy being present within the last five years; patients are also excluded if their previous cancer treatment contraindicates this protocol therapy
- Patients who have received prior radiotherapy to any portion of the abdominal cavity or pelvis are excluded; prior radiation for localized cancer of the breast, head and neck, or skin is permitted, provided that it was completed more than three years prior to registration, and the patient remains free of recurrent or metastatic disease
- Patients who have received prior chemotherapy for any abdominal or pelvic tumor within the last five years are excluded; patients may have received prior adjuvant chemotherapy for localized breast cancer, provided that it was completed more than three years prior to registration, and that the patient remains free of recurrent or metastatic disease
- Patients with acute hepatitis or active infection that requires parenteral antibiotics
- Patients with serious non-healing wound, ulcer, or bone fracture; this includes history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 28 days; patients with granulating incisions healing by secondary intention with no evidence of fascial dehiscence or infection are eligible but require weekly wound examinations
- Patients with active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major vessels
- Patients with history or evidence upon physical examination of central nervous system (CNS) disease, including primary brain tumor, seizures or history of seizures, and/or any CNS metastases are ineligible
- Patients with history of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage within six months of the first date of treatment on this study are ineligible
- +14 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- National Cancer Institute (NCI)lead
- NRG Oncologycollaborator
Study Sites (23)
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, 35233, United States
University of Colorado Hospital
Aurora, Colorado, 80045, United States
Augusta University Medical Center
Augusta, Georgia, 30912, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637, United States
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, 52242, United States
MedStar Franklin Square Medical Center/Weinberg Cancer Institute
Baltimore, Maryland, 21237, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Roswell Park Cancer Institute
Buffalo, New York, 14263, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
Case Western Reserve University
Cleveland, Ohio, 44106, United States
MetroHealth Medical Center
Cleveland, Ohio, 44109, United States
Cleveland Clinic Cancer Center/Fairview Hospital
Cleveland, Ohio, 44111, United States
Cleveland Clinic Foundation
Cleveland, Ohio, 44195, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
Riverside Methodist Hospital
Columbus, Ohio, 43214, United States
Hillcrest Hospital Cancer Center
Mayfield Heights, Ohio, 44124, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111, United States
Women and Infants Hospital
Providence, Rhode Island, 02905, United States
University of Virginia Cancer Center
Charlottesville, Virginia, 22908, United States
Virginia Commonwealth University/Massey Cancer Center
Richmond, Virginia, 23298, United States
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, 53792, United States
Related Publications (2)
Gillen J, Miller A, Bell-McGuinn KM, Schilder RJ, Walker JL, Mathews CA, Duska LR, Guntupalli SR, O'Cearbhaill R, Hays J, Hagemann AR, Gray HJ, Gordon SW, Armstrong DK, Chen A, Fracasso PM, Aghajanian C, Moore KN. Post hoc analyses of GOG 9923: Does BRCA status affect toxicities?: An NRG oncology study. Gynecol Oncol. 2021 May;161(2):512-515. doi: 10.1016/j.ygyno.2021.01.037. Epub 2021 Feb 17.
PMID: 33610319DERIVEDMoore KN, Miller A, Bell-McGuinn KM, Schilder RJ, Walker JL, O'Cearbhaill RE, Guntupalli SR, Armstrong DK, Hagemann AR, Gray HJ, Duska LR, Mathews CA, Chen A, O'Malley D, Gordon S, Fracasso PM, Aghajanian C. A phase I study of intravenous or intraperitoneal platinum based chemotherapy in combination with veliparib and bevacizumab in newly diagnosed ovarian, primary peritoneal and fallopian tube cancer. Gynecol Oncol. 2020 Jan;156(1):13-22. doi: 10.1016/j.ygyno.2019.10.012. Epub 2019 Nov 7.
PMID: 31708167DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Katherine M Bell-McGuinn
NRG Oncology
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 2, 2009
First Posted
October 5, 2009
Study Start
October 28, 2009
Primary Completion
September 2, 2016
Study Completion
April 10, 2020
Last Updated
October 20, 2021
Record last verified: 2021-10