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

A Phase II Evaluation of the Poly (ADP-Ribose) Polymerase (PARP)-1 and -2 Inhibitor Veliparib (ABT-888) (NSC#737664) in the Treatment of Persistent or Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Patients Who Carry a Germline BRCA1 or BRCA2 Mutation

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01540565

Enrollment

Registered

2012-02-29

Start date

2012-04-09

Completion date

2018-01-27

Last updated

2019-07-23

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

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

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.

Interventions

OTHERLaboratory Biomarker Analysis

Correlative studies

DRUGVeliparib

Given PO

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

FEMALE

Age

18 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
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.
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.

Secondary

Measure	Time frame	Description
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.

Other

Measure	Time frame	Description
SNPs With DNA Repair Genes, Tumor Response, PFS, OS, and Patient Demographics (e.g. Age, Race, Tumor Grade)	Baseline	If the clinical trial goes to the second stage and there is sufficient variability in the SNPs, then patients can be categorized by the nature of their SNPs and assessed for prognostic value through survival analysis (e.g. log-rank tests and Cox proportional hazards modeling). If the variability in SNPs is relatively low, assessment of prognostic value can be conducted with odds ratios of patients responding or surviving progression-free for at least 6 months. These techniques will use exact methods such as Fisher's exact test.
BRCA Mutation in Primary Tumor Tissue	Baseline	BRCA mutational status will be tabulated against the germline mutation to see what proportion of patients have a mutation reversal within the tumor and whether such reversals can explain resistance to the regimen under study.

Countries

United States

Participant flow

Recruitment details

Study opened to patient entry April 2012 and closed to accrual November 2012.

Participants by arm

Arm	Count
Treatment (Veliparib) Patients receive veliparib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Veliparib: Given PO	50
Total	50

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Ineligible	2

Baseline characteristics

Characteristic	Treatment (Veliparib)
Age, Customized 20-29 years	0 Participants
Age, Customized 30-39 years	2 Participants
Age, Customized 40-49 years	15 Participants
Age, Customized 50-59 years	14 Participants
Age, Customized 60-69 years	15 Participants
Age, Customized 70-79 years	2 Participants
Age, Customized >=80 years	2 Participants
Cell Type Other	9 Participants
Cell Type Serous	41 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	1 Participants
Race (NIH/OMB) Black or African American	2 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants
Race (NIH/OMB) White	44 Participants
Sex: Female, Male Female	50 Participants
Sex: Female, Male Male	0 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	21 / 50
other Total, other adverse events	48 / 50
serious Total, serious adverse events	10 / 50

Outcome results

Primary

Proportion of Patients With Adverse Events as Assessed by CTCAE v4.0

Patients with grade 3 or greater Adverse Events (AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported.

Time frame: After every cycle while on study therapy. Followed for late adverse events up to 30 days after completing therapy.