Veliparib and Radiation Therapy in Treating Patients With Advanced Solid Malignancies With Peritoneal Carcinomatosis, Epithelial Ovarian, Fallopian, or Primary Peritoneal Cancer
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, epithelial ovarian, fallopian, or primary peritoneal cancer. 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 with radiation therapy may kill more tumor cells.
Recurrent Fallopian Tube Cancer
Recurrent Ovarian Epithelial Cancer
Recurrent Primary Peritoneal Cavity Cancer
Unspecified Adult Solid Tumor, Protocol Specific
Radiation: radiation therapy
Other: laboratory biomarker analysis
Other: quality-of-life assessment
|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 With Two Additional Dose Levels in Patients With Epithelial Ovarian, Fallopian or Primary Peritoneal Cancers and Intra-abdominal Disease|
- Maximum tolerable dose defined as the highest dose at which 0 or 1 dose-limiting toxicities are observed in six patients as graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ 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 as graded by the NCI CTCAE version 4.0 [ 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.
- Clinical activity assessed by response (complete, partial, and overall), measured by RECIST 1.1 criteria [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]Reported descriptively.
- Microsatellite instability (MSI) [ Time Frame: Baseline ] [ Designated as safety issue: No ]MSI will be correlated with response using a Fisher exact test and correlated with progression-free survival (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.
- Presence of DNA repair proteins [ Time Frame: Baseline ] [ Designated as safety issue: No ]The presence of ERCC1, XRCC1, BRCA1, BRCA2, and PAR will be categorized by the level of staining: none, mild or strong. These data will be correlated with response and toxicity using the Cochran-Armitage trend test and logistic regression modeling.
- Changes in quality of life, assessed using the QLQC-30 standardized questionnaire [ Time Frame: From baseline to 4 years ] [ Designated as safety issue: No ]The change in score will be evaluated with a paired t-test. Subscale scores of the quality of life questionnaire will be similarly analyzed.
|Study Start Date:||January 2011|
|Estimated Primary Completion Date:||March 2015 (Final data collection date for primary outcome measure)|
Experimental: Treatment (veliparib, LDRWAR)
Patients receive veliparib PO BID on days 1-21 (days 5-21 of course 1). Patients undergo LDFWAR in BID on days 1 and 5 of weeks 1-3. Courses repeat every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity.
Other Name: ABT-888Radiation: radiation therapy
Other Names:Other: laboratory biomarker analysis
Correlative studiesOther: quality-of-life assessment
Other Name: quality of life assessment
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; at dose levels 5 and 6: to determine the maximum tolerable dose of veliparib in combination with LDFWAR in patients with epithelial ovarian, fallopian or primary peritoneal cancers with intraabdominal disease.
II. Determine the safety and toxicity of the combination of veliparib in conjunction with LDFWAR in patients with peritoneal carcinomatosis from advanced solid malignancies; at dose levels 5 and 6: to determine the safety and toxicity of veliparib in combination with LDFWAR in patients with epithelial ovarian, fallopian or primary peritoneal cancers with intraabdominal disease.
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; at dose levels 5 and 6: to assess the clinical activity of veliparib plus LDFWAR in patients with epithelial ovarian, fallopian or primary peritoneal cancer and intraabdominal disease as assessed by response rate by 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 receive veliparib orally (PO) twice daily (BID) on days 1-21 (days 5-21 of course 1). Patients undergo LDFWAR in BID on days 1 and 5 of weeks 1-3. Courses repeat every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 2 months.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01264432
|United States, Maryland|
|Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center||Recruiting|
|Baltimore, Maryland, United States, 21287|
|Contact: Nilofer S. Azad 410-614-9169 email@example.com|
|Principal Investigator: Nilofer S. Azad|
|University of Maryland/Greenebaum Cancer Center||Recruiting|
|Baltimore, Maryland, United States, 21201|
|Contact: Margit N. Horiba 410-328-6373 firstname.lastname@example.org|
|Principal Investigator: Margit N. Horiba|
|University Health Network-Princess Margaret Hospital||Recruiting|
|Toronto, Ontario, Canada, M5G 2M9|
|Contact: Lillian L. Siu 416-946-2911 Lilllian.email@example.com|
|Principal Investigator: Lillian L. Siu|
|Principal Investigator:||Nilofer Azad||Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center|