Veliparib, Pembrolizumab, and Combination Chemotherapy in Treating Patient With Locally Advanced Rectal Cancer

Inclusion Criteria

• The patient must have signed and dated an Institutional Review Board (IRB)-approved consent form that conforms to federal and institutional guidelines
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
• Diagnosis of adenocarcinoma of the rectum with the major portion of the tumor intact; Note: prior to randomization, the investigator must specify and document each of the following:
• Distance of the lowest tumor margin from the anal verge; and
• Intent for sphincter sparing or non-sphincter sparing surgical resection according to the primary surgeon; and
• The majority of the untreated tumor must be = 1.0 cm in any axis on cross sectional or endoscopic imaging; Note: nodes must measure 1.0 cm or greater to be considered positive for this eligibility requirement
• Not a candidate for sphincter-sparing surgical resection prior to neoadjuvant therapy (as planned by the primary surgeon)
• Note: clinical stage of the primary tumor and nodes may be determined locally by rectal endoscopic ultrasound or pelvic MRI (pelvic MRI is strongly preferred); CT scan with IV contrast is acceptable provided there is evidence of T4 and/or N2 disease
• Patients must have the ability to swallow and retain oral medication
• Absolute neutrophil count (ANC) must be >= 1200/mm^3 (within 28 days before randomization)
• Platelet count must be >= 100, 000/mm^3 (within 28 days before randomization)
• Hemoglobin must be >= 10 g/dL (within 28 days before randomization)
• Total bilirubin must be = ULN to 1.5 x ULN due to Gilbert's disease or similar syndrome involving slow conjugation of bilirubin (within 28 days before randomization)
• Alkaline phosphatase must be = = ULN but = 60 mL/min (within 28 days before randomization)
• Serum potassium, magnesium, and calcium levels within 28 days before randomization must be within normal limits (WNL) for the lab
• International normalized ratio of prothrombin time (INR) within 28 days before randomization must be = = 200 cells/uL within 30 days before beginning study therapy
• Be off all antiretroviral therapy (prophylaxis/treatment) more than 60 days before beginning study therapy, and
• Have no evidence of opportunistic infections
• Pregnancy test (urine or serum beta-human chorionic gonadotropin [HCG]) done within 72 hours before randomization must be negative (for women of childbearing potential only); if urine pregnancy results are positive or cannot be confirmed as negative, a serum pregnancy test will be required

Exclusion Criteria

• Rectal cancer histology other than adenocarcinoma (i.e., sarcoma, lymphoma, squamous cell carcinoma, mucosal melanoma, etc.)
• Definitive clinical or radiologic evidence of metastatic disease; required imaging studies must have been performed within 28 days prior to randomization; Note: Distant clinical staging to exclude patients with overt metastatic disease is determined by:
• Chest: CT scan (preferred); chest x-ray posterioranterior (PA) and lateral (acceptable); or positron emission tomography (PET) scan (acceptable)
• Abdomen: CT scan with IV contrast (preferred); or MRI (acceptable)
• Pelvis: MRI (preferred) or CT scan with IV contrast (acceptable)
• (It is recommended that the same imaging tests that are performed before randomization be used at follow-up time points; Note: CT scans of the abdomen and pelvis must be performed with IV contrast)
• History of prior invasive rectal malignancy, regardless of disease-free interval
• Cardiac disease that would preclude the use of any of the drugs included in the GI002 treatment regimen; this includes but is not limited to:
• Clinically unstable cardiac disease, including unstable atrial fibrillation, symptomatic bradycardia, unstable congestive heart failure, active myocardial ischemia, or indwelling temporary pacemaker
• Ventricular tachycardia or supraventricular tachycardia that requires treatment with class Ia antiarrhythmic drugs (e.g., quinidine, procainamide, disopy