Veliparib in Treating Patients With Malignant Solid Tumors That Do Not Respond to Previous Therapy
A Phase 1 Study of Chronically-Dosed, Single-Agent ABT-888 in Patients With Either BRCA 1/2 -Mutated Cancer; Platinum-Refractory Ovarian, Fallopian Tube, or Primary Peritoneal Cancer; or Basal-Like Breast Cancer
13 other identifiers
interventional
98
1 country
7
Brief Summary
This phase I trial studies the side effects and best dose of veliparib in treating patients with malignant solid tumors that do not respond to previous therapy. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Apr 2009
Longer than P75 for phase_1
7 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
April 20, 2009
CompletedFirst Submitted
Initial submission to the registry
May 1, 2009
CompletedFirst Posted
Study publicly available on registry
May 4, 2009
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 19, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
May 19, 2017
CompletedJune 29, 2018
June 1, 2018
8.1 years
May 1, 2009
June 28, 2018
Conditions
Outcome Measures
Primary Outcomes (1)
MTD, DLT, recommended phase II dose of chronically dosed single-agent veliparib in patients with either a refractory BRCA 1/2- mutated solid cancer; platinum- refractory ovarian, fallopian tube, or primary peritoneal cancer; or basal-like breast cancer
28 days
Secondary Outcomes (6)
Incidence of toxicities as assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
Up to 30 days post-treatment
Response (complete response, partial response, stable disease) evaluated using the Response Evaluation Criteria in Solid Tumors
Up to 4 weeks post-treatment
Pharmacokinetic parameters
Prior to taking veliparib on day 1, 4, and 15 then 30 minutes, 1 hour, 1½, 2, 3, 4, 6, and 8 hours after taking veliparib on day 1 and 15, and 24 hours after taking day 1 and day 15 doses of veliparib
Changes in PAR in PBMCs and tumor biopsies
Baseline to 4 weeks post-treatment
Changes in gamma-H2A histone family, member X (H2AX) in PBMCs and tumor biopsies
Baseline to 4 weeks post-treatment
- +1 more secondary outcomes
Study Arms (1)
Treatment (veliparib)
EXPERIMENTALPatients receive veliparib PO BID\* on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. NOTE: \*Patients receive veliparib once on day 1 of course 1 for pharmacokinetic and pharmacodynamic studies.
Interventions
Eligibility Criteria
You may qualify if:
- Patients must have histologically or cytologically confirmed solid tumors that fulfill at least one of the following 3 criteria:
- Have a documented BRCA1/2 mutation and a BRCA related malignancy (primarily breast or ovarian cancers, but also may include prostate or pancreatic cancers); NOTE: Patients enrolled under the Dose Expansion Phase must have a documented BRCA 1/2 mutation; or
- Platinum-refractory ovarian, fallopian tube, or primary peritoneal cancer or
- Basal-like breast cancer whose disease has progressed following standard therapy or who have no acceptable standard treatment options
- All patients without a known, documented BRCA mutation from Myriad Genetic Laboratories must have a probability of harboring a BRCA gene mutation assessed by BRCAPRO computer program
- All patients in whom the probability of having a genetic mutation is \>= 20% must have formal BRCA testing done through Myriad Genetic Laboratories in order to participate in the study
- Although various research based tests have been developed to detect BRCA mutations, due to the fact that these are not Food and Drug Administration (FDA) or Clinical Laboratory Improvement Amendments (CLIA) approved and therefore not reportable to patients, if a patient has diagnosis of a BRAC mutation based on a non-Myriad test, then they must undergo Myriad BRCA gene sequencing to be eligible
- Patients are eligible whether they have a known deleterious BRCA 1 or 2 mutation or a mutation of uncertain significance
- If a patient refuses BRCA testing, then they are ineligible for the study
- Platinum-refractory is defined as progression or recurrence within 6 months of initial platinum response; platinum-resistant is defined as having no prior response to platinum (i.e. evidence of progression within 2-3 cycles of beginning initial platinum-based treatment) and platinum-resistant patients are excluded; the only platinum-sensitive patients that are eligible are those with known BRCA mutations
- Basal-like breast cancer will be defined as estrogen and progesterone receptor negative, human epidermal growth factor receptor 2 (HER2) negative, and/or having expression profile of epidermal growth factor receptor (EGFR) and cytokeratins 5/6, consistent with basal phenotype; breast cancer patients with "triple-negative" phenotype (negative hormone and HER2 receptors) are eligible to participate in this trial; patients who are only known to be "triple-negative" but unknown basal phenotype will have their tumor blocks assessed for basal markers
- For subjects enrolled under the Dose Escalation Phase: Enrolled patients without a known BRCA mutation must have archived tumor tissue available for assessment of BRCA 1/2 protein expression by immunohistochemistry, as well as other correlative studies; it is optional for patients with a known BRCA mutation to provide archived tissue for correlative studies
- For subjects enrolled under the Dose Expansion Phase: All patients enrolled during the Dose Expansion Phase (for which a tissue biopsy is mandatory) must have a known BRCA mutation and must agree to collection or archival tumor tissue, if available
- There are no limitations on the amount of prior therapies received; however, no major surgery, radiation or chemotherapy within four weeks prior to study enrollment except for mitomycin C and nitrosoureas, in which case it is 6 weeks; patients must be recovered from toxicities of prior therapies to at least eligibility levels
- Eastern Cooperative Oncology Group (ECOG) performance status \< 2 (Karnofsky \> 60%)
- +12 more criteria
You may not qualify if:
- Patients who have had chemotherapy, hormone therapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
- Patients may not be receiving any other investigational agents
- Patients with prostate cancer must continue ongoing luteinizing-hormone-releasing hormone (LhRH) agonist therapy and discontinue antiandrogens at least 6 weeks (for bicalutamide) or 4 weeks (flutamide) prior to study entry; patients with bone metastases or hypercalcemia who began intravenous bisphosphonate treatment prior to study entry may continue this treatment
- Patients with CNS metastases must be stable after therapy for CNS metastases (such as surgery, radiotherapy or stereotactic radiosurgery) for \> 3 months and must be off steroid treatment prior to study enrollment and must have a life expectancy secondary to that of 3 months or greater to be eligible
- Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Human immunodeficiency virus (HIV) infected patients on protease inhibitors are ineligible; HIV infected patients with adequate cluster of differentiation 4 (CD4) counts (\> 500) and not on protease inhibitors are eligible
- Pregnant women are excluded; breastfeeding should be discontinued if the mother is treated with ABT-888
- Active seizure or history of seizure disorder
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (7)
City of Hope Comprehensive Cancer Center
Duarte, California, 91010, United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817, United States
City of Hope South Pasadena
South Pasadena, California, 91030, United States
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08903, United States
Penn State Milton S Hershey Medical Center
Hershey, Pennsylvania, 17033-0850, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Shannon Puhalla
University of Pittsburgh Cancer Institute (UPCI)
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 1, 2009
First Posted
May 4, 2009
Study Start
April 20, 2009
Primary Completion
May 19, 2017
Study Completion
May 19, 2017
Last Updated
June 29, 2018
Record last verified: 2018-06