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Carboplatin, Paclitaxel, Bevacizumab, and Veliparib in Treating Patients With Newly Diagnosed Stage II-IV Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cancer

Information source: National Cancer Institute (NCI)
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Ovarian Brenner Tumor; Ovarian Carcinosarcoma; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mixed Epithelial Tumor; Ovarian Mucinous Adenocarcinoma; Ovarian Serous Adenocarcinoma; Ovarian Transitional Cell Carcinoma; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer; Undifferentiated Ovarian Carcinoma

Intervention: Bevacizumab (Biological); Carboplatin (Drug); Cisplatin (Drug); Laboratory Biomarker Analysis (Other); Paclitaxel (Drug); Veliparib (Drug)

Phase: Phase 1

Status: Recruiting

Sponsored by: National Cancer Institute (NCI)

Official(s) and/or principal investigator(s):
Katherine Bell-McGuinn, Principal Investigator, Affiliation: NRG Oncology

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 tumor blood vessels. Giving veliparib together with carboplatin, paclitaxel, and bevacizumab may kill more tumor cells.

Clinical Details

Official title: 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

Study design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

Incidence of DLTs occurring in the first 4 courses of treatment (feasibility phase)

Incidence of dose-limiting toxicities (DLTs) occurring in the first or second course of treatment (dose-escalation phase)

Secondary outcome:

Change in PARP inhibition in PBMCs

Genomic BRCA mutation status

Incidence of toxicity, graded according to National Cancer Institute CTCAE version 4.0

Objective tumor response (complete and partial response) as assessed by the Response Evaluation Criteria in Solid Tumors (RECIST)

Progression-free survival

Detailed description: PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD) and dose-limiting toxicities of ABT-888 (veliparib) when administered using continuous versus intermittent dosing schedules with intravenous carboplatin, paclitaxel and bevacizumab using two different treatment regimens; or with intraperitoneal cisplatin and intravenous and intraperitoneal paclitaxel and bevacizumab in women with newly diagnosed, previously untreated, epithelial ovarian, fallopian tube, or primary peritoneal cancer. II. To determine the feasibility of these treatment regimens over four cycles in a 2-stage group sequential design once the MTD is established. III. To assess the toxicity of these regimens using Cancer Therapy Evaluation Program (CTEP) National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4. 0. SECONDARY OBJECTIVES: I. To estimate the response rate (in measurable disease patients) and progression-free survival in patients treated with these treatment regimens. TERTIARY OBJECTIVES: I. To assess the extent of poly-ADP-ribose polymerase (PARP) inhibition in peripheral blood mononuclear cells (PBMCs) on day 1 of cycles 1 and 2. II. To assess genomic breast cancer, early onset (BRCA) mutation status in all patients in regimens I and II with continuous ABT-888 dosing and descriptively correlate with toxicity and efficacy. OUTLINE: This is a dose-escalation study of veliparib followed by a feasibility study. Patients are sequentially assigned to 1 of 3 treatment regimens. REGIMEN I: Patients receive paclitaxel intravenously (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 orally (PO) twice daily (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: Patients 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: Patients receive paclitaxel IV over 3 hour on day 1 and intraperitoneally (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. After completion of study treatment, patients are followed up periodically.

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Female.

Criteria:

Inclusion Criteria:

- 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

- Patients must be entered between 1 and 12 weeks after initial surgery performed for

the combined purpose of diagnosis, staging and cytoreduction

- Patients who have met the pre-entry requirements specified

- Patients must have signed an approved informed consent and authorization permitting

release of personal health information Exclusion Criteria:

- 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

- Uncontrolled hypertension, defined as systolic > 150 mm Hg or diastolic > 90 mm Hg

- Myocardial infarction or unstable angina < 6 months prior to registration

- New York Heart Association (NYHA) class II or higher congestive heart failure

- Serious cardiac arrhythmia requiring medication

- CTEP CTCAE version 4. 0, grade 2 or higher peripheral ischemia (brief [< 24 hours

(hrs)] episode of ischemia managed non-surgically and without permanent deficit)

- Patients with known hypersensitivity to Chinese hamster ovary cell products or other

recombinant human or humanized antibodies

- Patients with clinically significant proteinuria (urine protein creatinine ratio

greater or equal to 1. 0)

- Patients with invasive procedures or anticipation of invasive procedures within the

following timeframes as defined below:

- Major surgical procedure, open biopsy or significant traumatic injury within 28

days prior to the first date of bevacizumab therapy (cycle 2)

- Major surgical procedure anticipated during the course of the study

- Core biopsy within 7 days prior to the first date of bevacizumab therapy (cycle

2)

- Patients who are pregnant or nursing

- Patients with clinical symptoms or signs of gastrointestinal obstruction and who

require parenteral hydration or nutrition

- Patients with GOG performance status of 3 or 4

Locations and Contacts

University of Colorado Cancer Center - Anschutz Cancer Pavilion, Aurora, Colorado 80045, United States; Recruiting
Kian Behbakht, Phone: 720-848-0650
Kian Behbakht, Principal Investigator

Georgia Regents University Medical Center, Augusta, Georgia 30912, United States; Recruiting
Sharad A. Ghamande, Phone: 706-721-1663, Email: cancer@georgiahealth.edu
Sharad A. Ghamande, Principal Investigator

University of Chicago Comprehensive Cancer Center, Chicago, Illinois 60637, United States; Recruiting
Meaghan E. Tenney, Phone: 773-834-7424
Meaghan E. Tenney, Principal Investigator

University of Iowa/Holden Comprehensive Cancer Center, Iowa City, Iowa 52242, United States; Recruiting
David P. Bender, Phone: 800-237-1225
David P. Bender, Principal Investigator

Johns Hopkins University/Sidney Kimmel Cancer Center, Baltimore, Maryland 21287, United States; Recruiting
Deborah K. Armstrong, Phone: 410-955-8804, Email: jhcccro@jhmi.edu
Deborah K. Armstrong, Principal Investigator

MedStar Franklin Square Medical Center/Weinberg Cancer Institute, Baltimore, Maryland 21237, United States; Active, not recruiting

Washington University School of Medicine, Saint Louis, Missouri 63110, United States; Recruiting
David G. Mutch, Phone: 800-600-3606, Email: info@ccadmin.wustl.edu
David G. Mutch, Principal Investigator

Roswell Park Cancer Institute, Buffalo, New York 14263, United States; Recruiting
Shashikant B. Lele, Phone: 877-275-7724
Shashikant B. Lele, Principal Investigator

Memorial Sloan-Kettering Cancer Center, New York, New York 10065, United States; Recruiting
Katherine M. Bell-McGuinn, Phone: 212-639-7202
Katherine M. Bell-McGuinn, Principal Investigator

Case Western Reserve University, Cleveland, Ohio 44106, United States; Withdrawn

Cleveland Clinic Cancer Center/Fairview Hospital, Cleveland, Ohio 44111, United States; Terminated

Cleveland Clinic Foundation, Cleveland, Ohio 44195, United States; Recruiting
Peter G. Rose, Phone: 866-223-8100
Peter G. Rose, Principal Investigator

MetroHealth Medical Center, Cleveland, Ohio 44109, United States; Recruiting
Peter G. Rose, Phone: 866-223-8100
Peter G. Rose, Principal Investigator

Ohio State University Comprehensive Cancer Center, Columbus, Ohio 43210, United States; Recruiting
Katherine M. Bell-McGuinn, Phone: 212-639-7202, Email: bell-mck@mskcc.org
Katherine M. Bell-McGuinn, Principal Investigator

Riverside Methodist Hospital, Columbus, Ohio 43214, United States; Terminated

Hillcrest Hospital Cancer Center, Mayfield Heights, Ohio 44124, United States; Recruiting
Peter G. Rose, Phone: 866-223-8100
Peter G. Rose, Principal Investigator

University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, United States; Recruiting
Robert S. Mannel, Phone: 405-271-4272, Email: julie-traylor@ouhsc.edu
Robert S. Mannel, Principal Investigator

Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, United States; Recruiting
Lainie P. Martin, Phone: 215-728-4790
Lainie P. Martin, Principal Investigator

Women and Infants Hospital, Providence, Rhode Island 02905, United States; Recruiting
Cara A. Mathews, Phone: 401-274-1122
Cara A. Mathews, Principal Investigator

University of Virginia Cancer Center, Charlottesville, Virginia 22908, United States; Recruiting
Linda R. Duska, Phone: 434-243-6143
Linda R. Duska, Principal Investigator

Virginia Commonwealth University/Massey Cancer Center, Richmond, Virginia 23298, United States; Recruiting
Jori S. Carter, Phone: 804-628-1939
Jori S. Carter, Principal Investigator

University of Wisconsin Hospital and Clinics, Madison, Wisconsin 53792, United States; Terminated

Additional Information

Starting date: October 2009
Last updated: July 22, 2015

Page last updated: August 23, 2015

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