Veliparib and Radiation Therapy in Treating Patients With Advanced Solid Malignancies With Peritoneal Carcinomatosis
This phase I trial studies the side effects and best dose of veliparib when given together with radiation therapy in treating patients with advanced solid malignancies with peritoneal carcinomatosis. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high energy x rays to kill tumor cells. Giving veliparib together with radiation therapy may kill more tumor cells.
Peritoneal Cavity Metastasis
Unspecified Adult Solid Tumor, Protocol Specific
Radiation: radiation therapy
Procedure: quality-of-life assessment
Other: laboratory biomarker analysis
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Study of Veliparib (ABT-888) in Combination With Low-dose Fractionated Whole Abdominal Radiation Therapy (LDFWAR) in Patients With Advanced Solid Malignancies With Peritoneal Carcinomatosis|
- Maximum tolerated dose of veliparib in combination with LDFWAR defined as the highest dose at which 0 or 1 dose-limiting toxicities are observed in six patients [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]Reported with exact binomial proportions and 95% confidence intervals.
- Proportion of toxicities of the combination of veliparib and LDRWAR [ Time Frame: Up to 4 weeks after completion of study treatment ] [ Designated as safety issue: Yes ]Reported by type and grade with exact binomial proportions and 95% confidence intervals.
- Response (complete, partial, and overall), measured by RECIST 1.1 criteria [ Time Frame: Up to 4 weeks after completion of study treatment ] [ Designated as safety issue: No ]Reported descriptively.
- Microsatellite instability (MSI) or levels of DNA repair proteins (ERCC1, XRCC1, BRCA1, BRCA2, PAR) compared to clinical activity of this regimen [ Time Frame: Baseline to 4 weeks after completion of study treatment ] [ Designated as safety issue: No ]MSI, determined positive or negative by PCR, will be correlated with response using a Fisher exact test and correlated with PFS using the log rank test and Kaplan-Meier curves. The effect of MSI on response and PFS, adjusting for other covariates, will be assessed using logistic regression and the Cox proportional hazards model. It is hypothesized that MSI will increase the probability of a response and prolong PFS.
- Changes in quality of life, assessed using the QLQC-30 standardized questionnaire [ Time Frame: From baseline to 2 months ] [ Designated as safety issue: No ]Evaluated using a paired t-test.
|Study Start Date:||January 2011|
|Estimated Primary Completion Date:||April 2014 (Final data collection date for primary outcome measure)|
Experimental: Treatment (veliparib, LDRWAR)
Patients will take veliparib PO BID on days 1-21. LDFWAR will be administered in two fractions every Monday and Friday for weeks 1-3 of each course. Courses will be 28 days long. Three courses only of LDFWAR will be administered.
Radiation: radiation therapy
Other Names:Drug: veliparib
Other Name: ABT-888Procedure: quality-of-life assessment
Other Name: quality of life assessmentOther: laboratory biomarker analysis
I. Determine the maximum tolerable dose of veliparib in combination with low-dose fractionated whole abdominal radiation therapy (LDFWAR) in patients with peritoneal carcinomatosis from advanced solid malignancies.
II. Determine the safety and toxicity of the combination of veliparib in conjunction with LDFWAR in patients with peritoneal carcinomatosis from advanced solid malignancies.
I. Assess clinical activity of veliparib plus LDFWAR in patients with peritoneal carcinomatosis from advanced solid malignancies as assessed by response rate by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.
II. Evaluate if microsatellite instability or baseline levels of various deoxyribonucleic acid (DNA) repair proteins (excision repair cross-complementing 1 [ERCC1], x-ray repair complementing defective repair in Chinese hamster cells 1 [XRCC1], breast cancer 1, early onset (BRCA1), breast cancer 2, early onset [BRCA2], poly [ADP-ribosyl]ation [PAR]) correlate with clinical activity of this regimen.
III. Evaluate changes in quality of life for patients treated with this regimen by serial measurements using the Quality of Life Questionnaire Core-30 (QLQC-30) standardized questionnaire.
OUTLINE: This is a dose escalation study of veliparib.
Patients will take veliparib orally (PO) twice daily (BID) on days 1-21. LDFWAR will be administered in two fractions every Monday and Friday for weeks 1-3 of each course. Courses will be 28 days long. Three courses only of LDFWAR will be administered.
After completion of study treatment, patients are followed up every 2 months.
|United States, Maryland|
|Johns Hopkins University|
|Baltimore, Maryland, United States, 21287-8936|
|University of Maryland Greenebaum Cancer Center|
|Baltimore, Maryland, United States, 21201-1595|
|University Health Network-Princess Margaret Hospital|
|Toronto, Ontario, Canada, M5G 2M9|
|Principal Investigator:||Nilofer Azad||Johns Hopkins University|