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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2012-02913 | Registry Identifier | CTRP (Clinical Trial Reporting Program) | |
| NA_00043143 | |||
| J1097 | |||
| NA_00043143, J1097 | |||
| CDR0000691881 | |||
| 8813 | Other Identifier | Johns Hopkins University/Sidney Kimmel Cancer Center | |
| 8813 | Other Identifier | CTEP | |
| P30CA006973 | U.S. NIH Grant/Contract | View source | |
| U01CA132123 | U.S. NIH Grant/Contract | View source | |
| U01CA070095 | U.S. NIH Grant/Contract | View source | |
| UM1CA186644 | U.S. NIH Grant/Contract | View source | |
| UM1CA186691 | U.S. NIH Grant/Contract | View source |
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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 (abnormal cells divide without control and can invade nearby tissues) 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.
PRIMARY OBJECTIVES:
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.
SECONDARY OBJECTIVES:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment (veliparib, LDRWAR) | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Laboratory Biomarker Analysis | Other | Correlative studies |
| |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | Reported with exact binomial proportions and 95% confidence intervals. | 28 days |
| Measure | Description | Time Frame |
|---|---|---|
| Changes in quality of life, assessed using the QLQC-30 standardized questionnaire | The change in score will be evaluated with a paired t-test. Subscale scores of the quality of life questionnaire will be similarly analyzed. | From baseline to 4 years |
| Clinical activity assessed by response (complete, partial, and overall), measured by RECIST 1.1 criteria |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Nilofer Azad | Johns Hopkins University/Sidney Kimmel Cancer Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Maryland/Greenebaum Cancer Center | Baltimore | Maryland | 21201 | United States | ||
| Johns Hopkins University/Sidney Kimmel Cancer Center |
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| Quality-of-Life Assessment |
| Other |
Ancillary studies |
|
|
| Radiation Therapy | Radiation | Undergo LDFWAR |
|
|
| Veliparib | Drug | Given PO |
|
|
Reported descriptively. |
| Up to 4 years |
| Microsatellite instability (MSI) | 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. | Baseline |
| Presence of DNA repair proteins | 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. | Baseline |
| Proportion of toxicities of the combination of veliparib and LDRWAR as graded by the NCI CTCAE version 4.0 | Reported by type and grade with exact binomial proportions and 95% confidence intervals. | Up to 4 weeks after completion of study treatment |
| Baltimore |
| Maryland |
| 21287 |
| United States |
| University Health Network-Princess Margaret Hospital | Toronto | Ontario | M5G 2M9 | Canada |
| ID | Term |
|---|---|
| D010534 | Peritoneal Neoplasms |
| D005185 | Fallopian Tube Neoplasms |
| D010051 | Ovarian Neoplasms |
| ID | Term |
|---|---|
| D000008 | Abdominal Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D004067 | Digestive System Neoplasms |
| D004066 | Digestive System Diseases |
| D010532 | Peritoneal Diseases |
| D005833 | Genital Neoplasms, Female |
| D014565 | Urogenital Neoplasms |
| D005184 | Fallopian Tube Diseases |
| D000291 | Adnexal Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D000091662 | Genital Diseases |
| D004701 | Endocrine Gland Neoplasms |
| D010049 | Ovarian Diseases |
| D004700 | Endocrine System Diseases |
| D006058 | Gonadal Disorders |
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| ID | Term |
|---|---|
| D011878 | Radiotherapy |
| D011827 | Radiation |
| C521013 | veliparib |
| ID | Term |
|---|---|
| D013812 | Therapeutics |
| D055585 | Physical Phenomena |
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