Study of Durvalumab (MEDI4736) After Chemo-Radiation for Microsatellite Stable Stage II-IV Rectal Cancer

Inclusion Criteria

• •The ECOG performance status must be 0 or 1
• •Patients with biopsy-proven adenocarcinoma, stage II- IV rectal cancer.
• •The tumor must have been determined to be mismatch repair proficient or microsatellite stable through CLIA approved testing (Immunohistochemistry \[IHC\], polymerase chain reaction \[PCR\], or Next-Generation Sequencing \[NGS\] assays).
• •Patients must be candidates for planned surgical resection of their primary rectal cancer 8 - 12 weeks after completion of neoadjuvant chemoRT, even if stage IV.
• •Planned neoadjuvant chemoRT treatment must conform to NCCN guidelines.
• •Baseline staging prior to chemoRT initiation must be obtained. If stage IV, there must be documentation by PET/CT scan, CT scan, or MRI, that the patient has evidence of measurable distant disease per RECIST 1.1. Note: Patients with stage IV disease should have limited but measurable metastatic disease (one or two organs involved e.g., liver and lung) and primary tumor deemed resectable.
• •Blood counts performed within 4 weeks prior to study entry must meet the following criteria:
• •* ANC must be greater than or equal to 1500/mm3
• •* Platelet count must be greater than or equal to 75,000/mm3; and
• •* Hemoglobin must be greater than or equal to 9 g/dL.
• •Adequate hepatic function performed within 4 weeks prior to study entry must be met:
• •* Total bilirubin must be less than or equal to 1.5 x ULN (upper limit of normal) for the lab unless the patient has a bilirubin elevation greater than 1.5 x Upper limit of normal (ULN) to 3 x ULN due to Gilbert's disease or similar syndrome involving slow conjugation of bilirubin; and
• •* AST and ALT must be less than or equal to 2.5 x ULN for the lab with the following exception: for patients with documented liver metastases, AST and ALT must be less than or equal to 5 x ULN.
• •Adequate renal function within 4 weeks of study entry, defined as serum creatinine less than or equal to 1.5 x ULN for the lab. (If creatinine is 1.0-1.5 x ULN, the creatinine clearance should be greater than 40 mL/min per Cockcroft-Gault formula (Cockcroft-Gault 1976), or by 24-hour urine collection for determination of creatinine clearance.)
• •Patients with reproductive potential (male/female) must agree to use accepted and highly effective methods of contraception while receiving durvalumab, and for at least 3 months after the last dose of durvalumab.
• •Ongoing or active gastritis or peptic ulcer disease.
• •Active bleeding diatheses which in the opinion of the treating physician poses a significantly increased operative risk.
• •Known history of previous diagnosis of tuberculosis.
• •History of hypersensitivity to durvalumab or any excipient.
• •Known history of active pneumonia, pneumonitis, symptomatic interstitial lung disease, or definitive evidence of interstitial lung disease described on CT scan, MRI, or chest x-ray in asymptomatic patients; dyspnea at rest requiring current continuous oxygen therapy.
• •Psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements, or interfere with interpretation of study results.
• •Pregnancy or lactation at the time of study entry. (Note: Pregnancy testing should be performed within 14 days prior to study entry according to institutional standards for women of childbearing potential.)
• •Use of any investigational agent within 4 weeks prior to study entry.