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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00989651
First received: October 2, 2009
Last updated: September 23, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Brenner Tumor
Ovarian Carcinosarcoma
Ovarian Clear Cell Cystadenocarcinoma
Ovarian Endometrioid Adenocarcinoma
Ovarian Mixed Epithelial Carcinoma
Ovarian Mucinous Cystadenocarcinoma
Ovarian Serous Cystadenocarcinoma
Ovarian Undifferentiated Adenocarcinoma
Stage IIA Fallopian Tube Cancer
Stage IIA Ovarian Epithelial Cancer
Stage IIA Primary Peritoneal Cavity Cancer
Stage IIB Fallopian Tube Cancer
Stage IIB Ovarian Epithelial Cancer
Stage IIB Primary Peritoneal Cavity Cancer
Stage IIC Fallopian Tube Cancer
Stage IIC Ovarian Epithelial Cancer
Stage IIC Primary Peritoneal Cavity Cancer
Stage IIIA Fallopian Tube Cancer
Stage IIIA Ovarian Epithelial Cancer
Stage IIIA Primary Peritoneal Cavity Cancer
Stage IIIB Fallopian Tube Cancer
Stage IIIB Ovarian Epithelial Cancer
Stage IIIB Primary Peritoneal Cavity Cancer
Stage IIIC Fallopian Tube Cancer
Stage IIIC Ovarian Epithelial Cancer
Stage IIIC Primary Peritoneal Cavity Cancer
Stage IV Fallopian Tube Cancer
Stage IV Ovarian Epithelial Cancer
Stage IV Primary Peritoneal Cavity Cancer
Drug: paclitaxel
Drug: carboplatin
Biological: bevacizumab
Drug: veliparib
Drug: cisplatin
Other: laboratory biomarker analysis
Phase 1

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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Incidence of dose-limiting toxicities (DLTs) occurring in the first or second course of treatment (dose-escalation phase) [ Time Frame: Up to day 42 ] [ Designated as safety issue: Yes ]
  • Incidence of DLTs occurring in the first 4 courses of treatment (feasibility phase) [ Time Frame: Up to day 84 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Objective tumor response (complete and partial response) as assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: Up to 11 years ] [ Designated as safety issue: No ]
    Tabulated by regimen and BRCA mutation status.

  • Progression-free survival [ Time Frame: Time from start of treatment to time of progression or death, assessed up to 11 years ] [ Designated as safety issue: No ]
    Summarized using Kaplan-Meier plots by BRCA mutation status.

  • Incidence of toxicity as assessed by NCI CTCAE version 4.0 [ Time Frame: Up to 30 days after last dose of treatment ] [ Designated as safety issue: Yes ]
    Tabulated by regimen and by BRCA mutation status.

  • Change in PARP inhibition in peripheral blood mononuclear cells (PBMCs) [ Time Frame: Day 1 to day 22 (day 1 of course 1 to day 1 of course 2) ] [ Designated as safety issue: No ]
    PARP inhibition in PBMCs in each course (courses 1 and 2) and the change from course1 to course 2 will be summarized by dose level and regimen using descriptive statistics (e.g., mean, standard deviation, median, quartiles) and using graphs. In addition, linear models may be used to assess the association between PARP inhibition and dose level with transformations of the PARP inhibition as appropriate.

  • Genomic BRCA mutation status [ Time Frame: Baseline ] [ Designated as safety issue: No ]

Estimated Enrollment: 96
Study Start Date: October 2009
Estimated Primary Completion Date: September 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Regimen I (paclitaxel, carboplatin, bevacizumab, veliparib)
Patients 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.
Drug: paclitaxel
Given IV or IP
Other Names:
  • Anzatax
  • Asotax
  • TAX
  • Taxol
Drug: carboplatin
Given IV
Other Names:
  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin
Biological: bevacizumab
Given IV
Other Names:
  • anti-VEGF humanized monoclonal antibody
  • anti-VEGF monoclonal antibody
  • Avastin
  • rhuMAb VEGF
Drug: veliparib
Given PO
Other Name: ABT-888
Other: laboratory biomarker analysis
Correlative studies
Experimental: Regimen II (paclitaxel, carboplatin, bevacizumab, veliparib)
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.
Drug: paclitaxel
Given IV or IP
Other Names:
  • Anzatax
  • Asotax
  • TAX
  • Taxol
Drug: carboplatin
Given IV
Other Names:
  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin
Biological: bevacizumab
Given IV
Other Names:
  • anti-VEGF humanized monoclonal antibody
  • anti-VEGF monoclonal antibody
  • Avastin
  • rhuMAb VEGF
Drug: veliparib
Given PO
Other Name: ABT-888
Other: laboratory biomarker analysis
Correlative studies
Experimental: Regimen III (paclitaxel, cisplatin, bevacizumab, veliparib)
Patients receive paclitaxel IV over 3 hour 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.
Drug: paclitaxel
Given IV or IP
Other Names:
  • Anzatax
  • Asotax
  • TAX
  • Taxol
Biological: bevacizumab
Given IV
Other Names:
  • anti-VEGF humanized monoclonal antibody
  • anti-VEGF monoclonal antibody
  • Avastin
  • rhuMAb VEGF
Drug: veliparib
Given PO
Other Name: ABT-888
Drug: cisplatin
Given IP
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP
Other: laboratory biomarker analysis
Correlative studies

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 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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00989651

Locations
United States, Colorado
University of Colorado Cancer Center - Anschutz Cancer Pavilion Recruiting
Aurora, Colorado, United States, 80045
Contact: Susan A. Davidson    720-848-0650      
Principal Investigator: Susan A. Davidson         
United States, Georgia
Georgia Regents University Medical Center Recruiting
Augusta, Georgia, United States, 30912
Contact: Sharad A. Ghamande    706-721-1663    cancer@georgiahealth.edu   
Principal Investigator: Sharad A. Ghamande         
United States, Illinois
University of Chicago Recruiting
Chicago, Illinois, United States, 60637
Contact: Meaghan E. Tenney    773-834-7424    julie-traylor@ouhsc.edu   
Principal Investigator: Meaghan E. Tenney         
United States, Iowa
University of Iowa Hospitals and Clinics Active, not recruiting
Iowa City, Iowa, United States, 52242
United States, Maryland
Franklin Square Hospital Center Active, not recruiting
Baltimore, Maryland, United States, 21237
Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center Recruiting
Baltimore, Maryland, United States, 21287
Contact: Deborah K. Armstrong    410-955-8804    jhcccro@jhmi.edu   
Principal Investigator: Deborah K. Armstrong         
United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: David G. Mutch    800-600-3606    info@ccadmin.wustl.edu   
Principal Investigator: David G. Mutch         
United States, New York
Memorial Sloan-Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Katherine M. Bell-McGuinn    212-639-7202      
Principal Investigator: Katherine M. Bell-McGuinn         
United States, Ohio
Cleveland Clinic Foundation Recruiting
Cleveland, Ohio, United States, 44195
Contact: Peter G. Rose    866-223-8100      
Principal Investigator: Peter G. Rose         
Case Western Reserve University Active, not recruiting
Cleveland, Ohio, United States, 44106
Cleveland Clinic Cancer Center/Fairview Hospital Terminated
Cleveland, Ohio, United States, 44111
MetroHealth Medical Center Recruiting
Cleveland, Ohio, United States, 44109
Contact: Peter G. Rose    866-223-8100      
Principal Investigator: Peter G. Rose         
Ohio State University Medical Center Recruiting
Columbus, Ohio, United States, 43210
Contact: Katherine M. Bell-McGuinn    212-639-7202    bell-mck@mskcc.org   
Principal Investigator: Katherine M. Bell-McGuinn         
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center Recruiting
Columbus, Ohio, United States, 43210
Contact: David M. O'Malley    866-627-7616    osu@emergingmed.com   
Principal Investigator: David M. O'Malley         
Riverside Methodist Hospital Active, not recruiting
Columbus, Ohio, United States, 43214
Hillcrest Hospital Cancer Center Recruiting
Mayfield Heights, Ohio, United States, 44124
Contact: Peter G. Rose    866-223-8100      
Principal Investigator: Peter G. Rose         
United States, Oklahoma
University of Oklahoma Health Sciences Center Recruiting
Oklahoma City, Oklahoma, United States, 73104
Contact: Robert S. Mannel    405-271-4272    julie-traylor@ouhsc.edu   
Principal Investigator: Robert S. Mannel         
United States, Pennsylvania
Fox Chase Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19111
Contact: Lainie P. Martin    215-728-4790      
Principal Investigator: Lainie P. Martin         
United States, Rhode Island
Women and Infants Hospital Recruiting
Providence, Rhode Island, United States, 02905
Contact: Cara A. Mathews    401-274-1122    julie-traylor@ouhsc.edu   
Principal Investigator: Cara A. Mathews         
United States, Virginia
University of Virginia Recruiting
Charlottesville, Virginia, United States, 22908
Contact: Linda R. Duska    434-243-6143      
Principal Investigator: Linda R. Duska         
Virginia Commonwealth University Recruiting
Richmond, Virginia, United States, 23298
Contact: Jori S. Carter    804-628-1939      
Principal Investigator: Jori S. Carter         
United States, Wisconsin
University of Wisconsin Hospital and Clinics Recruiting
Madison, Wisconsin, United States, 53792
Contact: David M. Kushner    877-405-6866      
Principal Investigator: David M. Kushner         
Sponsors and Collaborators
Investigators
Principal Investigator: Katherine Bell-McGuinn NRG Oncology
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00989651     History of Changes
Other Study ID Numbers: NCI-2011-03730, NCI-2011-03730, CDR0000656038, GOG-9923, GOG-9923, U10CA027469, U10CA180868
Study First Received: October 2, 2009
Last Updated: September 23, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Adenocarcinoma
Neoplasms, Glandular and Epithelial
Ovarian Neoplasms
Fallopian Tube Neoplasms
Peritoneal Neoplasms
Cystadenocarcinoma
Cystadenocarcinoma, Serous
Cystadenocarcinoma, Mucinous
Carcinosarcoma
Mixed Tumor, Mullerian
Carcinoma
Carcinoma, Endometrioid
Brenner Tumor
Neoplasms by Histologic Type
Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Fallopian Tube Diseases
Abdominal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Peritoneal Diseases
Neoplasms, Cystic, Mucinous, and Serous

ClinicalTrials.gov processed this record on September 30, 2014