Overview

This trial is active, not recruiting.

Conditions brca1 mutation carrier, brca2 mutation carrier, ovarian epithelial tumor, recurrent fallopian tube carcinoma, recurrent ovarian carcinoma, recurrent primary peritoneal carcinoma
Treatments laboratory biomarker analysis, veliparib
Phase phase 2
Target PARP
Sponsor National Cancer Institute (NCI)
Start date April 2012
End date April 2017
Trial size 51 participants
Trial identifier NCT01540565, CDR0000726699, GOG-0280, NCI-2012-00684, U10CA027469, U10CA180868

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
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 ABT-888
Given PO

Primary Outcomes

Measure
Incidence of adverse effects as assessed by CTCAE v 4.0
time frame: Up to 5 years
The frequency of patients who have objective tumor response
time frame: Up to 5 years

Secondary Outcomes

Measure
Duration of OS
time frame: Up to 5 years
Duration of PFS
time frame: Up to 5 years
The proportion of patients who survive progression-free for at least 6 months
time frame: 6 months

Eligibility Criteria

Female participants at least 18 years old.

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

Additional Information

Official title 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
Principal investigator Robert Coleman
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.
Trial information was received from ClinicalTrials.gov and was last updated in November 2016.
Information provided to ClinicalTrials.gov by National Cancer Institute (NCI).