Primary objective:
To evaluate whether therapy with nivolumab following combined modality therapy (CMT) improves disease-free survival (DFS) compared with observation in patients with high risk anal carcinoma.

Secondary objectives:

  • 1a. To compare nivolumab following combined modality therapy (CMT) with observation in patients with high risk anal carcinoma with regard to:
  • 1b. Objective response rate (complete [CR] and partial [PR]), stable disease and progression.
  • 1c. Severe toxicity interval.
  • 1d. Colostomy-free survival.
  • 1e. Overall survival.
  • 1f. Toxicity.

Inclusion Criteria:

  1. Patients must have histologically proven stage IIB (T3N0M0 only), IIIA (T2N1M0), IIIB (T4N0M0), or IIIC (T3N1M0, T4N1M0) invasive squamous cell carcinoma of the anus or anorectum, according to the American Joint Committee on Cancer (AJCC) 8th edition; this may include tumors of non-keratinizing histology such as basaloid, transitional cell, or cloacogenic histology; individuals with squamous cell carcinoma of the anal margin are eligible if there is evidence of extension of the primary tumor into the anal canal
  2. Patients must have Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
  3. Patients must have hemoglobin levels of > 9 g/dL (within 2 weeks prior to registration)
  4. Patient must have a platelet count of > 100,000/mm^3 (within 2 weeks prior to registration)
  5. Patient's absolute neutrophil count (ANC) level must be > 1500/mm^3 (within 2 weeks prior to registration)
  6. Serum creatinine must be =< 1.5 X upper limit of normal (ULN) (within 2 weeks prior to registration)
  7. Total bilirubin must be < 2 X ULN (within 2 weeks prior to registration)
  8. Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 2.5 X institutional upper limit of normal (within 2 weeks prior to registration)
  9. Albumin >= 3.0 g/dL (within 2 weeks prior to registration)
  10. Patients known to be human immunodeficiency virus (HIV)+ are permitted; patients with CD4 > 200 and serum HIV viral load of < 200 copies/mm^3 are eligible, and SEE PROTOCOL FOR ADDITIONAL TESTING REQUIREMENTS FOR HIV+ SUBJECTS.

    NOTE: HIV testing is not required for eligibility

  11. For patients registering prior to start of chemoradiotherapy, baseline scans must have been completed within 4 weeks prior to registration
  12. Women of child bearing potential and sexually active males must use accepted and effective method(s) of contraception and/or abstain from sexual intercourse while on protocol treatment and for at least 5 months after the last dose of nivolumab (for female patients) and for at least 7 months after the last dose of nivolumab (for male patients)
  13. Any surgery must have been completed >= 4 weeks prior to starting study treatment
  14. No 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
  15. No prior treatment with an immune checkpoint inhibitor (anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA4 monoclonal antibody)
  16. No patients with immunodeficiency or receiving systemic steroid therapy equivalent to > 10 mg prednisone per day or any other form of immunosuppressive therapy within 7 days prior to Step 1 registration; topical corticosteroid or occasional inhaled corticosteroids are allowed
  17. No live vaccines within 30 days prior to registration; examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, yellow fever, rabies, BCG, and typhoid (oral) vaccine; seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines and are not allowed

    NOTE: no live vaccines may be administered while participating in the trial

  18. Previously irradiated patients (Arm S) must have received radiation per National Comprehensive Cancer Network guidelines; radiation therapy delivered on protocol (Arm T) will be reviewed
Clinical Program: Gastroinstestinal Cancer Program
Primary Sponsor: ECOG-ACRIN
Contact Info: 2029941161