Veliparib in Treating Patients With Persistent or Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

Phase 2

Completed

Conditions: BRCA2 Mutation Carrier
Recurrent Fallopian Tube Carcinoma
Ovarian Epithelial Tumor
Recurrent Ovarian Carcinoma
BRCA1 Mutation Carrier
Recurrent Primary Peritoneal Carcinoma

Interventions: Other: Laboratory Biomarker Analysis
Drug: Veliparib

Registration Number: NCT01540565

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: This phase II trial studies how well veliparib works in treating patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer that has come back or does not respond to treatment. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed Description: PRIMARY OBJECTIVES:

I. To estimate the proportion of patients who have objective tumor response (complete or partial).

II. To determine the frequency and severity of adverse events associated with treatment with veliparib (ABT-888) as assessed by the Active Version of the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

SECONDARY OBJECTIVES:

I. To determine the duration of progression-free survival (PFS) and overall survival (OS).

II. To determine the proportion of patients who survive progression-free for at least 6 months.

TERTIARY OBJECTIVES:

I. To explore the association between single nucleotide polymorphisms (SNPs) in deoxyribonucleic acid (DNA) repair genes (e.g., breast cancer \[BRCA\]1, Fanconi) and clinical characteristics, response, and patient outcome (PFS and OS).

OUTLINE:

Patients receive veliparib orally (PO) twice daily (BID) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 52

Inclusion Criteria

Patients must have recurrent or persistent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma AND carry a germline mutation in BRCA1 or BRCA2 (confirmation required via Myriad test report); histologic documentation of the original primary tumor is required via the pathology report
All patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors(RECIST)1.1; measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded); each lesion must be >= 10 mm when measured by computed tomography (CT), magnetic resonance imaging (MRI), or caliper measurement by clinical exam; or >= 20 mm when measured by chest x-ray; lymph nodes must be >= 15 mm in short axis when measured by CT or MRI
Patient must have at least one "target lesion" to be used to assess response on this protocol as defined by RECIST; tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy
Patients who have received one prior cytotoxic regimen must have a Gynecological Oncology Group (GOG) performance status of 0, 1, or 2
Patients who have received two or three prior cytotoxic regimens must have a GOG performance status of 0 or 1
Recovery from effects of recent surgery, radiotherapy, or chemotherapy
- Patients should be free of active infection requiring antibiotics (with the exception of uncomplicated urinary tract infection [UTI])
- Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to registration; continuation of hormone replacement therapy is permitted
- Any other prior therapy directed at the malignant tumor, including chemotherapy, biologic/targeted (non-cytotoxic) agents and immunologic agents, must be discontinued at least three weeks prior to registration; patients receiving nitrosoureas or mitomycin C must discontinue 6 weeks prior to registration
- Any prior radiation therapy must be discontinued at least four weeks prior to registration
Prior therapy
- Patients must have had one prior platinum-based chemotherapeutic regimen for management of primary disease containing carboplatin, cisplatin, or another organoplatinum compound; this initial treatment may have included intraperitoneal therapy, consolidation, biologic/targeted (non-cytotoxic) agents or extended therapy administered after surgical or non-surgical assessment
- Patients are allowed to receive, but are not required to receive, two additional cytotoxic regimens for management of recurrent or persistent disease
- Patients are allowed to receive, but are not required to receive, biologic/targeted (non-cytotoxic) therapy for management of recurrent or persistent disease; patients are allowed to receive, but are not required to receive, biologic/targeted (non-cytotoxic) therapy as part of their primary treatment regimen
- Patients with both platinum-sensitive and platinum-resistant disease are eligible; patients with platinum-refractory disease are NOT eligible
- Definitions:
  - Platinum sensitive ovarian cancer is defined as patients who respond to platinum-based therapy (complete or partial) and then progress/recur more than 6 months after their last platinum dose (i.e., platinum-free interval is > 6 months)
  - Platinum resistant ovarian cancer is defined as patients who respond to platinum-based therapy (complete or partial) and then progress/recur within 6 months of their last platinum dose (i.e., platinum-free interval is =< 6 months)
  - Platinum refractory ovarian cancer is defined as patients who have progression of disease while receiving platinum-based chemotherapy or who fail to achieve at least a partial response to platinum-based chemotherapy (i.e., best response to platinum-based chemotherapy is stable disease)
Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl
Platelets greater than or equal to 100,000/mcl
Creatinine less than or equal to 1.5 x institutional upper limit normal (ULN)
Bilirubin less than or equal to 1.5 x ULN
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 3 x ULN
Alkaline phosphatase less than or equal to 2.5 x ULN
Patients must have signed an approved informed consent and authorization permitting release of personal health information
Patients of childbearing potential must have a negative pregnancy test prior to the study entry and be practicing an effective form of contraception

Exclusion Criteria

Patients who have had previous treatment with veliparib (ABT-888) or any other poly (adenosine diphosphate [ADP]-ribose) polymerase 1 (PARP) inhibitor (including olaparib); note: Iniparib (BSI-201) cannot inhibit PARP1 at pharmacologically achievable concentrations, therefore prior iniparib therapy is allowed
Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancer and other specific malignancies, are excluded if there is any evidence of other malignancy being present within the last three 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 OTHER THAN for the treatment of ovarian, fallopian tube, or primary peritoneal cancer within the last three years 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 OTHER THAN for the treatment of ovarian, fallopian tube, or primary peritoneal cancer within the last three 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 seizures or history or seizures are ineligible
Patients with history or evidence upon physical examination of central nervous system (CNS) disease, including primary brain tumor, any CNS metastases, or 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; patients with CNS metastases must be stable for > 3 months after treatment and off steroid treatment prior to study enrollment
Inability or unwillingness to swallow pills
Patients with clinical symptoms or signs of gastrointestinal obstruction and/or who require parenteral hydration or nutrition
Patients who are pregnant or nursing

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (veliparib)	Laboratory Biomarker Analysis	Patients receive veliparib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Treatment (veliparib)	Veliparib	Patients receive veliparib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Proportion of Patients With Adverse Events as Assessed by CTCAE v4.0	After every cycle while on study therapy. Followed for late adverse events up to 30 days after completing therapy.	Patients with grade 3 or greater Adverse Events (AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported.
Proportion of Patients With Complete and Partial Tumor Response	CT scan/MRI if used to follow lesion for measurable disease every other cycle for the first 6 months, then every 3 months until progression. Repeat at other times if clinically indicated.Responses require confirmation at >= 4 wks from first documentation.	Patients with complete and partial tumor response by RECIST V1.1 (per response evaluation criteria in Solid Tumors Criteria (RECIST V1.1) for target lesions and assessed by MRI (CT scan): Complete Response (CR), disappearance of all target lesions (confirmed at \>= 4 weeks); Partial Response (PR) \>= 30% decrease in the sum of the longest diameter of target lesions (confirmed at \>= 4 weeks); Overall Response = CR + PR.

Secondary Outcome Measures

Name	Time	Method
The Proportion of Patients Who Survive Progression-free for at Least 6 Months	6 months	This outcome captures whether or not the patient survived progression-free for at least 6 months, and is displayed as a proportion.
Duration of OS	Every cycle while patient is receiving protocol therapy. Patients will be monitored for survival after going off therapy for a 5 year period, every 3 months for the first 2 years, then every 6 months for the last 3 years.	Overall survival
Duration of PFS	CT scan/MRI if used to follow lesion for measurable disease every other cycle for the first 6 months, then every 3 months until progression. Patients who begin subsequent therapy without progression will be monitored for PFS for 5 years.	The time from randomization until disease progression, death, or date of last contact. Endpoints are progression or death. Patients who are not observed with an endpoint are censored. Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions (and \>= 5 mm increase of target lesions), or a measurable increase in a non-target lesion, or the appearance of new lesions.

Trial Locations

Locations (153): Northwestern University
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Chicago, Illinois, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
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Baltimore, Maryland, United States
The Hospital of Central Connecticut
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New Britain, Connecticut, United States
Sinai Hospital of Baltimore
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Baltimore, Maryland, United States
Marshfield Clinic - Weston Center
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Weston, Wisconsin, United States
Seattle Cancer Care Alliance
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Seattle, Washington, United States
Women's Cancer Center of Nevada
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Las Vegas, Nevada, United States
Abbott-Northwestern Hospital
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Minneapolis, Minnesota, United States
Duke University Medical Center
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Durham, North Carolina, United States
UC San Diego Moores Cancer Center
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La Jolla, California, United States
John Muir Medical Center-Concord Campus
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Concord, California, United States
Gynecologic Oncology Associates-Newport Beach
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Newport Beach, California, United States
UC Irvine Health/Chao Family Comprehensive Cancer Center
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Orange, California, United States
Stanford Cancer Institute Palo Alto
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Palo Alto, California, United States
Northside Hospital
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Atlanta, Georgia, United States
Northeast Georgia Medical Center-Gainesville
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Gainesville, Georgia, United States
University of Hawaii Cancer Center
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Honolulu, Hawaii, United States
Decatur Memorial Hospital
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Decatur, Illinois, United States
University of Chicago Comprehensive Cancer Center
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Chicago, Illinois, United States
Loyola University Medical Center
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Maywood, Illinois, United States
Sudarshan K Sharma MD Limted-Gynecologic Oncology
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Hinsdale, Illinois, United States
Saint Vincent Hospital and Health Care Center
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Indianapolis, Indiana, United States
Memorial Medical Center
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Springfield, Illinois, United States
McFarland Clinic PC - Ames
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Ames, Iowa, United States
Iowa Methodist Medical Center
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Des Moines, Iowa, United States
Medical Oncology and Hematology Associates-Des Moines
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Des Moines, Iowa, United States
Iowa-Wide Oncology Research Coalition NCORP
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Des Moines, Iowa, United States
Medical Oncology and Hematology Associates-Laurel
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Des Moines, Iowa, United States
Mercy Medical Center - Des Moines
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Des Moines, Iowa, United States
Iowa Lutheran Hospital
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Des Moines, Iowa, United States
Cancer Center of Kansas - Winfield
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Winfield, Kansas, United States
Fairview Ridges Hospital
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Burnsville, Minnesota, United States
Union Hospital of Cecil County
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Elkton, Maryland, United States
Fairview-Southdale Hospital
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Edina, Minnesota, United States
Hutchinson Area Health Care
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Hutchinson, Minnesota, United States
Park Nicollet Clinic - Saint Louis Park
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Saint Louis Park, Minnesota, United States
Regions Hospital
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Saint Paul, Minnesota, United States
Lakeview Hospital
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Stillwater, Minnesota, United States
Rice Memorial Hospital
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Willmar, Minnesota, United States
Cancer Research for the Ozarks NCORP
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Springfield, Missouri, United States
CoxHealth South Hospital
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Springfield, Missouri, United States
Cooper Hospital University Medical Center
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Camden, New Jersey, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
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New York, New York, United States
Memorial Sloan Kettering Cancer Center
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New York, New York, United States
Hope Women's Cancer Centers-Asheville
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Asheville, North Carolina, United States
Carolinas Medical Center/Levine Cancer Institute
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Charlotte, North Carolina, United States
Summa Akron City Hospital/Cooper Cancer Center
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Akron, Ohio, United States
Rutherford Hospital
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Rutherfordton, North Carolina, United States
Cleveland Clinic Foundation
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Cleveland, Ohio, United States
Case Western Reserve University
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Cleveland, Ohio, United States
Cleveland Clinic Cancer Center/Fairview Hospital
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Cleveland, Ohio, United States
Ohio State University Comprehensive Cancer Center
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Columbus, Ohio, United States
Lake University Ireland Cancer Center
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Mentor, Ohio, United States
Riverside Methodist Hospital
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Columbus, Ohio, United States
Hillcrest Hospital Cancer Center
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Mayfield Heights, Ohio, United States
Oklahoma Cancer Specialists and Research Institute-Tulsa
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Tulsa, Oklahoma, United States
Bryn Mawr Hospital
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Bryn Mawr, Pennsylvania, United States
Paoli Memorial Hospital
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Paoli, Pennsylvania, United States
University of Pennsylvania/Abramson Cancer Center
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Philadelphia, Pennsylvania, United States
Pennsylvania Hospital
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Philadelphia, Pennsylvania, United States
Women and Infants Hospital
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Providence, Rhode Island, United States
Saint Francis Hospital
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Greenville, South Carolina, United States
Lankenau Medical Center
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Wynnewood, Pennsylvania, United States
Main Line Health NCORP
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Wynnewood, Pennsylvania, United States
AnMed Health Cancer Center
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Anderson, South Carolina, United States
M D Anderson Cancer Center
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Houston, Texas, United States
Baylor All Saints Medical Center at Fort Worth
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Fort Worth, Texas, United States
PeaceHealth Medical Group PC
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Bellingham, Washington, United States
University of Vermont Medical Center
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Burlington, Vermont, United States
Harrison HealthPartners Hematology and Oncology-Bremerton
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Bremerton, Washington, United States
Harrison Medical Center
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Bremerton, Washington, United States
Providence Regional Cancer Partnership
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Everett, Washington, United States
Skagit Valley Hospital Regional Cancer Care Center
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Mount Vernon, Washington, United States
Harrison HealthPartners Hematology and Oncology-Poulsbo
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Poulsbo, Washington, United States
Pacific Gynecology Specialists
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Seattle, Washington, United States
Fred Hutchinson Cancer Research Center
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Seattle, Washington, United States
Kaiser Permanente Washington
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Seattle, Washington, United States
Swedish Medical Center-First Hill
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Seattle, Washington, United States
Northwest Hospital
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Seattle, Washington, United States
Cancer Care Northwest - Spokane South
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Spokane, Washington, United States
Olympic Medical Cancer Care Center
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Sequim, Washington, United States
University of Washington Medical Center
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Seattle, Washington, United States
MultiCare Tacoma General Hospital
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Tacoma, Washington, United States
Rockwood Cancer Treatment Center-DHEC-Downtown
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Spokane, Washington, United States
Wenatchee Valley Hospital and Clinics
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Wenatchee, Washington, United States
Saint Joseph Medical Center
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Tacoma, Washington, United States
Providence Saint Mary Regional Cancer Center
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Walla Walla, Washington, United States
Green Bay Oncology at Saint Vincent Hospital
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Green Bay, Wisconsin, United States
Saint Vincent Hospital Cancer Center Green Bay
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Green Bay, Wisconsin, United States
Bay Area Medical Center
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Marinette, Wisconsin, United States
Marshfield Clinic
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Marshfield, Wisconsin, United States
Holy Family Memorial Hospital
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Manitowoc, Wisconsin, United States
ProHealth Waukesha Memorial Hospital
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Waukesha, Wisconsin, United States
Aurora West Allis Medical Center
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West Allis, Wisconsin, United States
Marshfield Clinic - Wisconsin Rapids Center
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Wisconsin Rapids, Wisconsin, United States
UCSF Medical Center-Mount Zion
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San Francisco, California, United States
Metro Minnesota Community Oncology Research Consortium
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Saint Louis Park, Minnesota, United States
Wichita NCI Community Oncology Research Program
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Wichita, Kansas, United States
Ridgeview Medical Center
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Waconia, Minnesota, United States
Saint Francis Regional Medical Center
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Shakopee, Minnesota, United States
Rocky Mountain Gynecologic Oncology PC
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Englewood, Colorado, United States
Hennepin County Medical Center
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Minneapolis, Minnesota, United States
Mercy Hospital
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Coon Rapids, Minnesota, United States
Cancer Center of Kansas - Wichita
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Wichita, Kansas, United States
Unity Hospital
🇺🇸
Fridley, Minnesota, United States
Cancer Center of Kansas - Parsons
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Parsons, Kansas, United States
Cancer Center of Kansas - Wellington
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Wellington, Kansas, United States
Cancer Center of Kansas - Fort Scott
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Fort Scott, Kansas, United States
Cancer Center of Kansas - Chanute
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Chanute, Kansas, United States
United Hospital
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Saint Paul, Minnesota, United States
Minnesota Oncology Hematology PA-Woodbury
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Woodbury, Minnesota, United States
Associates In Womens Health
🇺🇸
Wichita, Kansas, United States
Minnesota Oncology Hematology PA-Maplewood
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Maplewood, Minnesota, United States
Via Christi Regional Medical Center
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Wichita, Kansas, United States
Cancer Center of Kansas - Newton
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Newton, Kansas, United States
New Ulm Medical Center
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New Ulm, Minnesota, United States
Cancer Center of Kansas - Dodge City
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Dodge City, Kansas, United States
Cancer Center of Kansas-Kingman
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Kingman, Kansas, United States
Cancer Center of Kansas-Liberal
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Liberal, Kansas, United States
Cancer Center of Kansas-Independence
🇺🇸
Independence, Kansas, United States
North Memorial Medical Health Center
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Robbinsdale, Minnesota, United States
Cancer Center of Kansas-Wichita Medical Arts Tower
🇺🇸
Wichita, Kansas, United States
Cancer Center of Kansas - Salina
🇺🇸
Salina, Kansas, United States
Saint John's Hospital - Healtheast
🇺🇸
Maplewood, Minnesota, United States
Cancer Center of Kansas - El Dorado
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El Dorado, Kansas, United States
Maine Medical Center-Bramhall Campus
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Portland, Maine, United States
Greenville Health System Cancer Institute-Eastside
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Greenville, South Carolina, United States
Marshfield Clinic-Rice Lake Center
🇺🇸
Rice Lake, Wisconsin, United States
Beebe Medical Center
🇺🇸
Lewes, Delaware, United States
Abington Memorial Hospital
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Abington, Pennsylvania, United States
Christiana Care Health System-Christiana Hospital
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Newark, Delaware, United States
Greenville Health System Cancer Institute-Seneca
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Seneca, South Carolina, United States
Washington University School of Medicine
🇺🇸
Saint Louis, Missouri, United States
Green Bay Oncology Limited at Saint Mary's Hospital
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Green Bay, Wisconsin, United States
Greenville Health System Cancer Institute-Faris
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Greenville, South Carolina, United States
Greenville Health System Cancer Institute-Spartanburg
🇺🇸
Spartanburg, South Carolina, United States
Marshfield Clinic Cancer Center at Sacred Heart
🇺🇸
Eau Claire, Wisconsin, United States
Huntsman Cancer Institute/University of Utah
🇺🇸
Salt Lake City, Utah, United States
Ascension Saint Mary's Hospital
🇺🇸
Rhinelander, Wisconsin, United States
Ascension Saint Michael's Hospital
🇺🇸
Stevens Point, Wisconsin, United States
Marshfield Clinic-Minocqua Center
🇺🇸
Minocqua, Wisconsin, United States
University of Wisconsin Hospital and Clinics
🇺🇸
Madison, Wisconsin, United States
Henry Ford Hospital
🇺🇸
Detroit, Michigan, United States
Saint Joseph's Hospital and Medical Center
🇺🇸
Phoenix, Arizona, United States
University of Oklahoma Health Sciences Center
🇺🇸
Oklahoma City, Oklahoma, United States
Nebraska Methodist Hospital
🇺🇸
Omaha, Nebraska, United States
Southeast Clinical Oncology Research (SCOR) Consortium NCORP
🇺🇸
Winston-Salem, North Carolina, United States
Aurora Saint Luke's Medical Center
🇺🇸
Milwaukee, Wisconsin, United States
Yale University
🇺🇸
New Haven, Connecticut, United States
Florida Hospital Orlando
🇺🇸
Orlando, Florida, United States
Norton Hospital Pavilion and Medical Campus
🇺🇸
Louisville, Kentucky, United States
Mercy Hospital Springfield
🇺🇸
Springfield, Missouri, United States
Cancer Center of Kansas - Pratt
🇺🇸
Pratt, Kansas, United States