Veliparib in Combination With Carboplatin and Paclitaxel in Treating Patients With Locally Advanced or Metastatic Solid Tumors
A Phase 1 Study of ABT-888 (Veliparib) in Combination With Weekly Carboplatin and Paclitaxel in Advanced Solid Tumors
6 other identifiers
interventional
22
1 country
3
Brief Summary
This phase I clinical trial studies the side effects and the best dose of veliparib when given together with carboplatin and paclitaxel in treating patients with locally advanced or metastatic solid tumors. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by blocking them from dividing. Giving veliparib with carboplatin and paclitaxel may work better in treating patients with solid tumors.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
3 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
January 1, 2011
CompletedFirst Submitted
Initial submission to the registry
January 20, 2011
CompletedFirst Posted
Study publicly available on registry
January 21, 2011
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 1, 2015
CompletedMay 25, 2015
May 1, 2015
4.2 years
January 20, 2011
May 22, 2015
Conditions
Outcome Measures
Primary Outcomes (1)
MTD defined as the dose level one level below the lowest dose where greater than or equal to 2 patients experience a DLT assessed by National Cancer Institute (NCI) CTCAE v. 4.0
21 days
Secondary Outcomes (6)
Change in BRCA protein levels by immunohistochemistry
Baseline to day 4 of course 2
Change in PAR and g-H2AX in tumor tissue
Baseline to day 4 of course 2
Grade >= 3 non-hematological or any grade 5 DLTs as graded by the NCI CTCAE v. 4.0
21 days
Incidence of adverse events as graded by the NCI CTCAE v. 4.0
Up to 4 weeks post-treatment
Plasma concentration of carboplatin, paclitaxel, and veliparib using liquid chromatography-mass spectrometry (LC-MS) assay and spectrometry assay
Baseline, at 30 minutes and at 1, 2, 4, and 8 hours on day 3 of course 1
- +1 more secondary outcomes
Study Arms (1)
Treatment (veliparib, paclitaxel, carboplatin)
EXPERIMENTALDOSE-ESCALATION: Patients receive veliparib PO twice daily BID on days 1-5, 8-12, and 15-19 and paclitaxel IV over 1 hour and carboplatin IV over 30 minutes in course 1 and 3 hours in subsequent courses on days 3, 10, and 17. After 4 courses, patients receive paclitaxel and carboplatin on days 3 and 10 only. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. (Completed as of 12/2012) EXPANSION COHORT: Patients receive veliparib PO BID on days 1-21 and paclitaxel IV over 1 hour and carboplatin IV over 3 hours on days 3 and 10. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Interventions
Given IV
Given IV
Given PO
Eligibility Criteria
You may qualify if:
- Histologically or cytologically confirmed solid tumor that has evidence of metastatic spread (stage IV) or is locally advanced and unresectable
- Patients with breast cancer may have estrogen receptor positive or negative (ER+ or ER-) disease
- Patients with breast cancer may not be human epidermal growth receptor -2 (HER2)-positive ( 3+), or fluorescent in situ hybridization (FISH) ratio \> 2.2
- Patients in the biopsy expansion cohort must have "triple negative" breast cancer defined as:
- Estrogen receptor staining \< 10%; progesterone receptor staining \<10%; Her 2 \< 2.2 by FISH, or immunohistochemistry (IHC) 0-2+
- Patients may have been previously treated
- In the dose escalation cohort, there is no limit to prior therapies
- In the expansion cohort, patients may have only had 1-3 prior regimens for metastatic disease
- Patients may have received prior carboplatin, paclitaxel, or poly (ADP-ribose) polymerase (PARP) inhibitor therapy as part of their previous treatment regimens
- However, patients may NOT have received prior therapy with paclitaxel, carboplatin, and PARP inhibitor in combination
- Patients must not have received chemotherapy within 4 weeks of starting study (or 6 weeks if prior treatment was with carmustine \[BCNU\] or mitomycin C)
- Patients must not have received radiation within 2 weeks of starting study
- Eastern Cooperative Oncology Group (ECOG) performance status (PS)\< 2 (Karnofsky \> 60%)
- Life expectancy \> 2 months
- Absolute neutrophil count (ANC) \>= 1,500/mcL
- +12 more criteria
You may not qualify if:
- Patients who have had chemotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) or radiotherapy within 2 weeks (4 weeks for central nervous system \[CNS\] metastases) 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
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to veliparib or other agents used in study
- Concurrent treatment with bisphosphonates, or other bone anti-resorptive agent such as denosumab is allowed; concurrent treatment with hormonal therapy (tamoxifen, ovarian suppression with gonadotropin-releasing hormone \[GNRH\] agonists, aromatase inhibitors) or trastuzumab therapy is NOT allowed in breast cancer patients; prostate cancer patients may continue GNRH agents
- 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
- Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with veliparib
- Active seizure or history of seizure disorder
- 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
- Patients who undergo biopsy as part of the study in the expanded dose cohort should not be on anti-coagulants or have a pre-existing coagulopathy
- Peripheral neuropathy of severity greater than grade 1
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (3)
Penn State Milton S Hershey Medical Center
Hershey, Pennsylvania, 17033-0850, United States
UPMC-Magee Womens Hospital
Pittsburgh, Pennsylvania, 15213, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention 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
January 20, 2011
First Posted
January 21, 2011
Study Start
January 1, 2011
Primary Completion
April 1, 2015
Last Updated
May 25, 2015
Record last verified: 2015-05