Inclusion Criteria:
- REGISTRATION TO STEP 1 ELIGIBILITY CRITERIA: 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
- REGISTRATION TO STEP 1 ELIGIBILITY CRITERIA: Patients must have Eastern Cooperative
Oncology Group (ECOG) performance status of 0-2
- REGISTRATION TO STEP 1 ELIGIBILITY CRITERIA: Patients must have hemoglobin levels of >
9 g/dL (within 2 weeks prior to registration)
- REGISTRATION TO STEP 1 ELIGIBILITY CRITERIA: Patient must have a platelet count of >
100,000/mm^3 (within 2 weeks prior to registration)
- REGISTRATION TO STEP 1 ELIGIBILITY CRITERIA: Patient's absolute neutrophil count (ANC)
level must be > 1500/mm^3 (within 2 weeks prior to registration)
- REGISTRATION TO STEP 1 ELIGIBILITY CRITERIA: Serum creatinine must be =< 1.5 X upper
limit of normal (ULN) (within 2 weeks prior to registration)
- REGISTRATION TO STEP 1 ELIGIBILITY CRITERIA: Total bilirubin must be < 2 X ULN (within
2 weeks prior to registration)
- REGISTRATION TO STEP 1 ELIGIBILITY CRITERIA: 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)
- REGISTRATION TO STEP 1 ELIGIBILITY CRITERIA: Albumin >= 3.0 g/dL (within 2 weeks prior
to registration)
- REGISTRATION TO STEP 1 ELIGIBILITY CRITERIA: 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 in addition:
- 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 20 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 and 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;
- NOTE: HIV testing is not required for eligibility
- REGISTRATION TO STEP 1 ELIGIBILITY CRITERIA: For patients registering prior to start
of chemoradiotherapy, baseline scans must have been completed within 4 weeks prior to
registration
- REGISTRATION TO STEP 1 ELIGIBILITY CRITERIA: 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)
- REGISTRATION TO STEP 1 ELIGIBILITY CRITERIA: Any surgery must have been completed >= 4
weeks prior to starting study treatment
- REGISTRATION TO STEP 1 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 1 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 1 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 Step 1 registration;
topical corticosteroid or occasional inhaled corticosteroids are allowed
- REGISTRATION TO STEP 1 ELIGIBILITY CRITERIA: 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
- REGISTRATION TO STEP 1 ELIGIBILITY CRITERIA: 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
- REGISTRATION TO STEP 2 ELIGIBILITY CRITERIA: Patients will be registered within 63
days following completion of standard chemoradiation for anal cancer; standard
chemoradiation therapy is as defined
- REGISTRATION TO STEP 2 ELIGIBILITY CRITERIA: 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 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
- REGISTRATION TO STEP 2 ELIGIBILITY CRITERIA: Patients must have received at least 54
gray (Gy) of radiation to the PTVp (primary) and 45 Gy to PTVn (elective nodal region)
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 >
10 g/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 =< 1.5 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: Patients known to be human
immunodeficiency virus (HIV)+ patients with CD4 > 200 and serum HIV viral load of <
200 copies/mm^3 are eligible; in addition:
- 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 20 weeks prior to enrollment; PPD positive (or Quantiferon assay
positive) participants are permitted if prophylaxis has been completed prior to
enrollment; NOTE: If patient completed chemoradiation on Step 1, PPD testing does
not need to be performed again
- 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)
- NOTE: HIV testing is not required for eligibility
- 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: 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)
- 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: 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
Exclusion Criteria:
- REGISTRATION TO STEP 1 ELIGIBILITY CRITERIA: For patients registering to Arm T,
patients must not have received prior chemoradiotherapy for anal cancer
- REGISTRATION TO STEP 1 ELIGIBILITY CRITERIA: Patients with an allogenic bone
marrow/stem, cell or solid organ transplant are excluded
- REGISTRATION TO STEP 1 ELIGIBILITY CRITERIA: Women MUST NOT be pregnant or
breast-feeding due to the potential teratogenic harm or abortifacient effects to an
unborn fetus and possible risk for adverse events in nursing infants with the
treatment regimens being used; all patients must also not expect to conceive or father
children from study registration and throughout their time on study treatment; for
female patients this must continue until at least 5 months after the last dose of
nivolumab and for male patients until at least 7 months after the last dose of
nivolumab; all females of child bearing potential must have a serum or urine pregnancy
test to rule out pregnancy within 2 weeks prior to registration; a female of
childbearing potential is any woman, regardless of sexual orientation or whether they
have undergone tubal ligation, who meets the following criteria: 1) has achieved
menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy,
or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does
not rule out childbearing potential) for at least 24 consecutive months (i.e., has had
menses at any time in the preceding 24 consecutive months)
- REGISTRATION TO STEP 1 ELIGIBILITY CRITERIA: Patients will be excluded if they have a
T1 or M1, and T2N0 cancer
- REGISTRATION TO STEP 1 ELIGIBILITY CRITERIA: Patients must not have had prior
potentially curative surgery (abdominal, peritoneal resection) for carcinoma of the
anus
- REGISTRATION TO STEP 1 ELIGIBILITY CRITERIA: Participants may not be receiving any
other standard anti-cancer therapy or experimental agent concurrently with the study
drugs
- REGISTRATION TO STEP 1 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 1 ELIGIBILITY CRITERIA: Patient must not have active autoimmune
disease in the past 2 years
- NOTE: This does not include patients with autoimmune disease controlled by
medication, such as hypothyroidism; this eligibility includes only patients with
endocrine disease controlled b
