Description
This randomized phase II clinical trial studies how well nivolumab after combined modality therapy works in treating patients with high risk stage II-IIIB anal cancer. Monoclonal antibodies, such as nivolumab, may interfere with the ability of tumor cells to grow and spread.
Eligibility
Inclusion Criteria
- REGISTRATION TO STEP 1 ELIGIBILITY CRITERIA
- Patients must have histologically proven stage II (T3N0 only), IIIA, or IIIB invasive anal (anal margin) squamous cell carcinoma; this may include tumors of non-keratinizing histology such as basaloid, transitional cell, or cloacogenic histology
- Patients must have Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- Patients must have hemoglobin levels of > 10g/dL within 2 weeks prior to registration
- Patient must have a platelet count of > 100,000/mm^3 within 2 weeks prior to registration
- Patient's absolute neutrophil count (ANC) level must be > 1500/mm^3 within 2 weeks prior to registration
- Serum creatinine must be =< 2 X upper limit of normal (ULN) within 2 weeks prior to registration
- Total bilirubin must be < 2 X ULN within 2 weeks prior to registration
- 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
- Albumin >= 3.0 g/dL within 2 weeks prior to registration
- Human immunodeficiency virus (HIV)+ patients with CD4 > 200 and serum HIV viral load of < 200 copies/mm^3 are permitted
- Participants must be purified protein derivative (PPD) negative; alternatively, the QuantiFERON-tuberculosis (TB) Gold In-Tube (QFT-GIT) assay (Cellestis Limited, Carnegie, Australia) can be used; an individual is considered positive for M. tuberculosis infection if the IFN-gamma response to TB antigens is above the test cut-off (after subtracting the background IFN-gamma response in the negative control); the result must be obtained within 12 weeks prior to enrollment; PPD positive (or Quantiferon assay positive) participants are permitted if prophylaxis has been completed prior to enrollment
- No history of acquired immune deficiency syndrome (AIDS)-related complications within past year other than a history of low CD4+ T-cell count (> 200/mm^3) prior to initiation of combination antiretroviral therapy; on study CD4+ T-cell count may not be informative due to chemoradiotherapy should not be used as an exclusion criterion if low
- Patient must be healthy on the basis of HIV disease with high likelihood of near normal life span were it not for the anal cancer
- Participants MUST receive appropriate care and treatment for HIV infection, including antiretroviral medications when clinically indicated, and should be under the care of a physician experienced in HIV management; participants will be eligible regardless of antiretroviral medication (including no antiretroviral medication) provided there is no intention to initiate therapy or the regimen has been stable for at least 4 weeks with no intention to change the regimen within 12 weeks following enrollment
- Patient must have =< grade 2 diarrhea (participants with grade 1 diarrhea are eligible provided stool for ova/parasites and stool cryptosporidium studies are negative
- For patients registering prior to start of chemoradiotherapy, baseline scans must have been completed within 4 weeks prior to registration
- Patients with an allogenic bone marrow/stem, cell or solid organ transplant are excluded
- Women of child-bearing potential must use an accepted and effective method of contraception and/or abstain from sexual intercourse while on protocol treatment and for at least 5 months after the last dose of nivolumab; sexually active males must use an accepted and effective method of contraception and/or abstain from sexual intercourse while on protocol treatment and for at least 7 months after the last dose of nivolumab
- Women must not be pregnant or breast-feeding; all females of childbearing potential must have a serum or urine pregnancy test to rule out pregnancy within 2 weeks prior to registration
- Pregnant women are excluded from this study; breastfeeding should be discontinued
- Patients will be excluded if they have a T1, T2N0 or M1 cancer
- Patients must not have had prior potentially curative surgery (abdominal, peritoneal resection) for carcinoma of the anus
- Participants may not be receiving any other standard anti-cancer therapy or experimental agent concurrently with the study drugs
- Any surgery must have been completed >= 4 weeks prior to starting study treatment
- 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
- Individuals with a history of a different malignancy are ineligible except if they have been disease-free for at least 2 years and are deemed by the investigator to be at low risk for recurrence; individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin
- Patient must not have active autoimmune disease that has required systemic treatment in past 2 years
- No prior treatment with an immune checkpoint inhibitor (anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA4 monoclonal antibody)
- 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 the first dose of study medication; topical corticosteroid or occasional inhaled corticosteroids are allowed
- 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
- Patients must not have known interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity
- Radiation therapy data are submitted to Imaging and Radiation Oncology Core (IROC) Rhode Island for quality review
- REGISTRATION TO STEP 2 ELIGIBILITY CRITERIA: Patients will be registered no sooner than 4 weeks following completion of standard chemoradiation for anal cancer; standard chemoradiation therapy
- REGISTRATION TO STEP 2 ELIGIBILITY CRITERIA: Patients must have histologically proven stage II (T3N0 only), IIIA, or IIIB invasive anal (anal margin) squamous cell carcinoma; this may include tumors of non-keratinizing histology such as basaloid, transitional cell, or cloacogenic histology
- REGISTRATION TO STEP 2 ELIGIBILITY CRITERIA: Patients must not have received less than 54 Gy of radiation for the treatment of the anal cancer
- REGISTRATION TO STEP 2 ELIGIBILITY CRITERIA: Patients must have ECOG performance status of 0-2
- REGISTRATION TO STEP 2 ELIGIBILITY CRITERIA: Patients must have hemoglobin levels of > 10g/dL within 2 weeks prior to registration
- REGISTRATION TO STEP 2 ELIGIBILITY CRITERIA: Patient must have a platelet count of > 100,000/mm^3 within 2 weeks prior to registration
- REGISTRATION TO STEP 2 ELIGIBILITY CRITERIA: Patient's ANC level must be > 1500/mm^3 within 2 weeks prior to registration
- REGISTRATION TO STEP 2 ELIGIBILITY CRITERIA: Serum creatinine must be =< 2 X ULN within 2 weeks prior to registration
- REGISTRATION TO STEP 2 ELIGIBILITY CRITERIA: Total bilirubin must be < 2 X ULN within 2 weeks prior to registration
- REGISTRATION TO STEP 2 ELIGIBILITY CRITERIA: AST (SGOT)/ALT (SGPT) =< 2.5 X institutional upper limit of normal within 2 weeks prior to registration
- REGISTRATION TO STEP 2 ELIGIBILITY CRITERIA: Albumin >= 3.0 g/dL within 2 weeks prior to registration
- REGISTRATION TO STEP 2 ELIGIBILITY CRITERIA: Human immunodeficiency virus (HIV)+ patients with CD4 > 200 and serum HIV viral load of < 200 copies/mm^3 are permitted
- Participants must be PPD negative; alternatively, the QuantiFERON-TB Gold In-Tube (QFT-GIT) assay (Cellestis Limited, Carnegie, Australia) can be used; an individual is considered positive for M. tuberculosis infection if the IFN-gamma response to TB antigens is above the test cut-off (after subtracting the background IFN-gamma response in the negative control); the result must be obtained within 12 weeks prior to enrollment; PPD positive (or Quantiferon assay positive) participants are permitted if prophylaxis has been completed prior to enrollment
- No history of AIDS-related complications within past year other than a history of low CD4+ T-cell count (> 200/mm^3) prior to initiation of combination antiretroviral therapy; on study CD4+ T-cell count may not be informative due to chemoradiotherapy should not be used as an exclusion criterion if low
- Patient must be healthy on the basis of HIV disease with high likelihood of near normal life span were it not for the anal cancer
- Participants MUST receive appropriate care and treatment for HIV infection, including antiretroviral medications when clinically indicated, and should be under the care of a physician experienced in HIV management; participants will be eligible regardless of antiretroviral medication (including no antiretroviral medication) provided there is no intention to initiate therapy or the regimen has been stable for at least 4 weeks with no intention to change the regimen within 12 weeks following enrollment
- Patient must have =< grade 2 diarrhea (participants with grade 1 diarrhea are eligible provided stool for ova/parasites and stool cryptosporidium studies are negative)
- REGISTRATION TO STEP 2 ELIGIBILITY CRITERIA: Scans done within 4 weeks of randomization to Step 2
- REGISTRATION TO STEP 2 ELIGIBILITY CRITERIA: Patient must have recovered from all toxicities associated with chemoradiotherapy for anal cancer, to grade =< 1 with the exception of alopecia
- REGISTRATION TO STEP 2 ELIGIBILITY CRITERIA: Patient must start treatment within 12 weeks of completion of chemoradiotherapy
- REGISTRATION TO STEP 2 ELIGIBILITY CRITERIA: Patients with an allogenic bone marrow/stem, cell or solid organ transplant are excluded
- REGISTRATION TO STEP 2 ELIGIBILITY CRITERIA: Women of child-bearing potential must use an accepted and effective method of contraception and/or abstain from sexual intercourse while on protocol treatment and for at least 5 months after the last dose of nivolumab; sexually active males must use an accepted and effective method of contraception and/or abstain from sexual intercourse while on protocol treatment and for at least 7 months after the last dose of nivolumab
- REGISTRATION TO STEP 2 ELIGIBILITY CRITERIA: Women must not be pregnant or breast-feeding; all females of childbearing potential must have a serum or urine pregnancy test to rule out pregnancy within 2 weeks prior to registration
- REGISTRATION TO STEP 2 ELIGIBILITY CRITERIA: Pregnant women are excluded from this study; breastfeeding should be discontinued
- REGISTRATION TO STEP 2 ELIGIBILITY CRITERIA: Patients must not have had prior potentially curative surgery (abdominal, peritoneal resection) for carcinoma of the anus
- REGISTRATION TO STEP 2 ELIGIBILITY CRITERIA: Participants may not be receiving any other standard anti-cancer therapy or experimental agent concurrently with the study drugs
- REGISTRATION TO STEP 2 ELIGIBILITY CRITERIA: 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
- REGISTRATION TO STEP 2 ELIGIBILITY CRITERIA: Individuals with a history of a different malignancy are ineligible except if they have been disease-free for at least 2 years and are deemed by the investigator to be at low risk for recurrence; individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin
- REGISTRATION TO STEP 2 ELIGIBILITY CRITERIA: Patient must not have active autoimmune disease that has required systemic treatment in past 2 years
- REGISTRATION TO STEP 2 ELIGIBILITY CRITERIA: No prior treatment with an immune checkpoint inhibitor (anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA4 monoclonal antibody)
- REGISTRATION TO STEP 2 ELIGIBILITY CRITERIA: 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 the first dose of study medication; topical corticosteroid or occasional inhaled corticosteroids are allowed
- REGISTRATION TO STEP 2 ELIGIBILITY CRITERIA: No live vaccines within 30 days prior to the first dose of trial treatment and while participating in the trial; 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
- REGISTRATION TO STEP 2 ELIGIBILITY CRITERIA: Patients must not have known interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity
- REGISTRATION TO STEP 2 ELIGIBILITY CRITERIA: Patients must not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to nivolumab
