Veliparib and Radiation Therapy in Treating Patients With Advanced Solid Malignancies With Peritoneal Carcinomatosis

• 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.
• 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.

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.

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.

II. Determine the safety and toxicity of the combination of veliparib in conjunction with LDFWAR in patients with peritoneal carcinomatosis from advanced solid malignancies.

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.

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 cycle. Cycles will be 28 days long. Three cycles only of LDFWAR will be administered.

After completion of study treatment, patients are followed up every 2 months.

• Peritoneal Carcinomatosis
• Peritoneal Cavity Metastasis
• Unspecified Adult Solid Tumor, Protocol Specific

• Radiation: radiation therapy
  Undergo LDFWAR
  Other Names:

  • irradiation
  • radiotherapy
  • therapy, radiation
• Drug: veliparib
  Given PO
  Other Name: ABT-888
• Procedure: quality-of-life assessment
  Correlative studies
  Other Name: quality of life assessment
• Other: laboratory biomarker analysis
  Correlative studies

Inclusion Criteria:

• Patients must have histologically proven solid malignancy that is metastatic or unresectable with metastatic peritoneal carcinomatosis; as this entity may be difficult to image, peritoneal disease can be documented through other modalities such as operative notes, clinical notes/symptoms, etc as well as imaging
• Patients must be refractory to standard therapy or have no acceptable standard treatment options
• Eastern Cooperative Oncology Group (ECOG) performance status =< 1
• Life expectancy of greater than 3 months
• Absolute neutrophil count (ANC) >= 1,500/mcL
• Platelets >= 100,000/mcL
• Total bilirubin =< 1.5 X upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) =< 2.5 X ULN
• Creatinine =< 1.5 X ULN OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
• Magnesium >= lower limit of normal (LLN)
• Calcium within normal limit (WNL)
• No surgery, hormonal therapy or chemotherapy within four weeks
• No previous abdominal radiation; if the patient has received previous pelvic radiation there should not be any overlap between the current and previous radiation fields
• Toxicities of prior chemotherapy recovered to grade 1 or less except for stable grade 2 peripheral neuropathy
• Negative pregnancy test if premenopausal; women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
• Archival tumor sample collection with a tumor block is required for all enrolled patients when available; if no block can be released per institutional policy, 10 to 20 unstained slides may be substituted; slides should have a positive charge and a thickness of 3 to 5 microns; if the only tissue sample available is a fine needle aspirate (FNA), the patient will still be considered eligible
• Patients with central nervous system (CNS) metastases to be stable after therapy for > 3 months and off steroid treatment prior to study enrollment

Exclusion Criteria:

• Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
• Patients who are currently receiving any other investigational agents
• Brain metastases: patients with treated and stable brain metastasis for 3 months, off steroids will be eligible
• Patients who demonstrate any clinical evidence of bleeding
• Patients who have demonstrated an inability to swallow oral medications
• Patients who have had a documented malignant bowel obstruction (unless patient had obstruction as their presenting symptom)
• Patients who have a known hypersensitivity to the components of the study drug, its analogs or drugs of a similar chemical or biologic composition
• 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; potential risks may also apply to other agents used in this study
• Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
• Patients who have uncontrolled ascites
• Patients with active seizures or a history of seizure are not eligible
• Patients previously treated with poly (ADP-ribose) polymerase 1 (PARP) inhibitors