Carboplatin, Paclitaxel, Bevacizumab, and ABT-888 in Treating Patients With Newly Diagnosed Stage II, Stage III, or Stage IV Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 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: June 23, 2014
Last verified: June 2014
  Purpose

This phase I trial is studying the side effects and best dose of ABT-888 when given together with carboplatin, paclitaxel, and bevacizumab in treating patients with newly diagnosed stage II, stage III, or stage IV ovarian epithelial cancer, fallopian tube cancer, or primary peritoneal cancer. 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 or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may stop the growth of tumor cells by blocking blood flow to the tumor. ABT-888 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving carboplatin, paclitaxel, and bevacizumab together with ABT-888 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
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:
  • 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 ]
  • 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 ]
  • 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.

  • Toxicity as assessed by NCI CTCAE v4.0 criteria [ Time Frame: Up to 30 days after last dose of drug treatment ] [ Designated as safety issue: Yes ]
  • Extent of poly-ADP-ribose polymerase (PARP) inhibition in peripheral blood mononuclear cells on day 1 of courses 1 and 2 [ Time Frame: Day 21 ] [ Designated as safety issue: No ]
  • Extent of PARP inhibition in peripheral blood mononuclear cells on day 1 of courses 1 and 2 [ Time Frame: Day 42 ] [ Designated as safety issue: No ]
  • Genomic BRCA mutation status [ Time Frame: Baseline ] [ Designated as safety issue: No ]

Estimated Enrollment: 96
Study Start Date: October 2009
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Regimen I (paclitaxel, carboplatin, bevacizumab)
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 oral ABT-888 twice daily 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
Other Names:
  • Anzatax
  • Asotax
  • TAX
  • Taxol
Drug: carboplatin
Given IV
Other Names:
  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin
Biological: bevacizumab
Given orally
Other Names:
  • anti-VEGF humanized monoclonal antibody
  • anti-VEGF monoclonal antibody
  • Avastin
  • rhuMAb VEGF
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 ABT-888 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
Other Names:
  • Anzatax
  • Asotax
  • TAX
  • Taxol
Drug: carboplatin
Given IV
Other Names:
  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin
Biological: bevacizumab
Given orally
Other Names:
  • anti-VEGF humanized monoclonal antibody
  • anti-VEGF monoclonal antibody
  • Avastin
  • rhuMAb VEGF
Drug: veliparib
Given IV
Other Name: ABT-888
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 when administered with carboplatin, paclitaxel, and bevacizumab using 2 different treatment regimens in patients with newly diagnosed stage II-IV ovarian epithelial, fallopian tube, or primary peritoneal cancer.

II. To determine the feasibility of these regimens over 4 courses once the MTD is established.

III. To assess the toxicity of these regimens using NCI CTCAE v4.0 criteria.

SECONDARY OBJECTIVES:

I. To estimate the response rate in patients with measurable disease. II. To estimate the progression-free survival of patients treated with these regimens.

III. To assess the extent of poly-ADP-ribose polymerase (PARP) inhibition in peripheral blood mononuclear cells on day 1 of courses 1 and 2.

IV. To assess genomic BRCA mutation status in all patients and descriptively correlate it with toxicity and efficacy.

OUTLINE: This is a multicenter, dose-escalation study of ABT-888 followed by a feasibility study. Patients are sequentially assigned to 1 of 2 treatment regimens.

REGIMEN I: 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 oral ABT-888 twice daily 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 ABT-888 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. Blood samples are collected periodically for biomarker analysis.

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:

  • Histologically confirmed newly diagnosed ovarian epithelial, fallopian tube, or primary peritoneal carcinoma, including one of the following histologic cell types:

    • Serous adenocarcinoma
    • Endometrioid adenocarcinoma
    • Mucinous adenocarcinoma
    • Undifferentiated carcinoma
    • Clear cell adenocarcinoma
    • Mixed epithelial adenocarcinoma
    • Transitional cell carcinoma
    • Malignant Brenner tumor
    • Adenocarcinoma not otherwise specified
    • Carcinosarcoma
  • Stage II-IV disease defined surgically with either optimal (≤ 1 cm) or suboptimal residual disease
  • Has undergone initial surgery for diagnosis, staging, and cytoreduction within the past 1-12 weeks
  • No current diagnosis of borderline ovarian epithelial tumor (formerly "tumors of low malignant potential") or recurrent invasive ovarian epithelial, primary peritoneal, or fallopian tube cancer treated with surgery only (e.g., stage IA or IB low-grade ovarian epithelial or fallopian tube cancers)

    • Patients with a prior diagnosis of a borderline tumor that was surgically resected and who subsequently developed an unrelated, new invasive ovarian epithelial, primary peritoneal, or fallopian tube cancer are eligible provided they have not received prior chemotherapy for any ovarian tumor
  • No prior or synchronous primary endometrial cancer, unless all of the following criteria are met:

    • Disease stage ≤ IB
    • No more than superficial myometrial invasion
    • No vascular or lymphatic invasion
    • No poorly differentiated subtypes, including papillary serous, clear cell, or other FIGO grade 3 lesions
  • No history or evidence of primary brain tumor or brain metastases by physical exam
  • GOG performance status 0-2
  • ANC ≥ 1,500/mm^3 (not induced or supported by granulocyte colony-stimulating factors)
  • Platelet count ≥ 100,000/mm^3
  • Creatinine ≤ 1.5 times upper limit of normal (ULN)
  • Bilirubin ≤ 1.5 times ULN
  • SGOT ≤ 2.5 times ULN
  • Alkaline phosphatase ≤ 2.5 times ULN
  • Albumin ≥ 3.0 g/dL
  • PT/INR ≤ 1.5 (or an in-range INR, usually between 2 and 3, if patient is on a stable dose of therapeutic warfarin)
  • PTT < 1.5 times ULN
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 3 months after completion of study treatment
  • No clinically significant proteinuria (i.e., urine protein:creatinine ratio ≥ 1.0)
  • No neuropathy (sensory and motor) > CTCAE grade 1
  • No acute hepatitis or active infection requiring parenteral antibiotics
  • No serious non-healing wound, ulcer, or bone fracture

    • Patients with granulating incisions healing by secondary intention are eligible provided there is no evidence of fascial dehiscence or infection and the patient undergoes weekly wound examinations
  • No abdominal fistula, gastrointestinal (GI) perforation, or intra-abdominal abscess within the past 28 days
  • No clinical symptoms or signs of GI obstruction and/or requirement for parenteral hydration or nutrition
  • No active bleeding or pathologic condition that carries a high risk of bleeding (e.g., known bleeding disorder, coagulopathy, or tumor involving major vessels)
  • No clinically significant cardiovascular disease, including any of the following:

    • Uncontrolled hypertension, defined as systolic BP > 150 mm Hg or diastolic BP > 90 mm Hg
    • Myocardial infarction or unstable angina within the past 6 months
    • NYHA class II-IV congestive heart failure
    • Serious cardiac arrhythmia requiring medication
    • Peripheral ischemia ≥ CTCAE grade 2 (at least brief [< 24 hours] episodes of ischemia managed non-surgically and without permanent deficit)
  • No cerebrovascular accident, transient ischemic attack, or subarachnoid hemorrhage within the past 6 months
  • No seizures not controlled with standard medical therapy or other evidence of CNS disease by physical exam
  • No other invasive malignancies within the past 5 years, except for nonmelanoma skin cancer and localized cancer of the breast or head and neck
  • No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies
  • No significant traumatic injury within the past 28 days
  • See Disease Characteristics
  • No prior cancer treatment that would contraindicate study therapy
  • More than 5 years since prior chemotherapy for any abdominal or pelvic tumor

    • Prior adjuvant chemotherapy for localized breast cancer is allowed provided it was completed > 3 years ago AND the patient remains free of recurrent or metastatic disease
  • No prior radiotherapy to any portion of the abdominal cavity or pelvis

    • Prior radiotherapy for localized cancer of the breast, head and neck, or skin is allowed provided it was completed > 3 years ago AND the patient remains free of recurrent or metastatic disease
  • More than 28 days since prior major surgical procedure or open biopsy
  • More than 7 days since prior core biopsy
  • No concurrent major surgical procedure
  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 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 Recruiting
Iowa City, Iowa, United States, 52242
Contact: David P. Bender    800-237-1225      
Principal Investigator: David P. Bender         
United States, Maryland
Franklin Square Hospital Center Active, not recruiting
Baltimore, Maryland, United States, 21237
Johns Hopkins University/Sidney Kimmel 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: Steven E. Waggoner    800-641-2422      
Principal Investigator: Steven E. Waggoner         
Case Western Reserve University Recruiting
Cleveland, Ohio, United States, 44106
Contact: Steven E. Waggoner    800-641-2422      
Principal Investigator: Steven E. Waggoner         
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         
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: Steven E. Waggoner    800-641-2422      
Principal Investigator: Steven E. Waggoner         
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         
Gynecologic Oncology Group Recruiting
Philadelphia, Pennsylvania, United States, 19103
Contact: Katherine M. Bell-McGuinn    212-639-7202      
Principal Investigator: Katherine M. Bell-McGuinn         
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: Andrew Poklepovic    804-628-1939      
Principal Investigator: Andrew Poklepovic         
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 Gynecologic Oncology Group
  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
Study First Received: October 2, 2009
Last Updated: June 23, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Adenocarcinoma
Brenner Tumor
Carcinoma
Carcinosarcoma
Mixed Tumor, Mullerian
Cystadenocarcinoma
Peritoneal Neoplasms
Fallopian Tube Neoplasms
Carcinoma, Endometrioid
Cystadenocarcinoma, Mucinous
Cystadenocarcinoma, Serous
Ovarian Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Fibroepithelial
Neoplasms, Fibrous Tissue
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Gonadal Disorders
Endocrine System Diseases
Neoplasms, Complex and Mixed
Sarcoma
Neoplasms, Cystic, Mucinous, and Serous
Abdominal Neoplasms

ClinicalTrials.gov processed this record on August 20, 2014