Veliparib and Radiation Therapy in Treating Patients With Advanced Solid Malignancies With Peritoneal Carcinomatosis, Epithelial Ovarian, Fallopian, or Primary Peritoneal Cancer
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|ClinicalTrials.gov Identifier: NCT01264432|
Recruitment Status : Completed
First Posted : December 21, 2010
Last Update Posted : November 21, 2017
|Condition or disease||Intervention/treatment||Phase|
|Adult Solid Neoplasm Peritoneal Carcinomatosis Recurrent Fallopian Tube Carcinoma Recurrent Ovarian Carcinoma Recurrent Primary Peritoneal Carcinoma||Other: Laboratory Biomarker Analysis Other: Quality-of-Life Assessment Radiation: Radiation Therapy Drug: Veliparib||Phase 1|
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 [adenosine diphosphate (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. Treatment repeats 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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||34 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Actual Study Start Date :||January 1, 2011|
|Actual Primary Completion Date :||November 15, 2016|
|Actual Study Completion Date :||November 15, 2016|
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. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Other: Quality-of-Life Assessment
Other Name: Quality of Life Assessment
Radiation: Radiation Therapy
- 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 ]Reported with exact binomial proportions and 95% confidence intervals.
- Changes in quality of life, assessed using the QLQC-30 standardized questionnaire [ Time Frame: From baseline to 4 years ]The change in score will be evaluated with a paired t-test. Subscale scores of the quality of life questionnaire will be similarly analyzed.
- Clinical activity assessed by response (complete, partial, and overall), measured by RECIST 1.1 criteria [ Time Frame: Up to 4 years ]Reported descriptively.
- Microsatellite instability (MSI) [ Time Frame: Baseline ]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 ]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.
- 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 ]Reported by type and grade with exact binomial proportions and 95% confidence intervals.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01264432
|United States, Maryland|
|University of Maryland/Greenebaum Cancer Center|
|Baltimore, Maryland, United States, 21201|
|Johns Hopkins University/Sidney Kimmel Cancer Center|
|Baltimore, Maryland, United States, 21287|
|University Health Network-Princess Margaret Hospital|
|Toronto, Ontario, Canada, M5G 2M9|
|Principal Investigator:||Nilofer Azad||Johns Hopkins University/Sidney Kimmel Cancer Center|