Trial Search Results

Nivolumab After Combined Modality Therapy in Treating Patients With High Risk Stage II-IIIB Anal Cancer

This phase III trial investigates how well nivolumab after combined modality therapy works in treating patients with high risk stage II-IIIB anal cancer. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Stanford is currently accepting patients for this trial.

Lead Sponsor:

National Cancer Institute (NCI)

Collaborator: Canadian Cancer Trials Group

Stanford Investigator(s):

Intervention(s):

  • Biological: Nivolumab
  • Other: Patient Observation

Phase:

Phase 3

Eligibility


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

Ages Eligible for Study

18 Years - N/A

Genders Eligible for Study

All

Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Umara Ahmed
650-498-6608
Recruiting