Research & Innovation

Colorectal Clinical Trials

Clinical Trials

Syndax SNDX-275-0601

A Phase 1b/2, Open-label, Dose Escalation Study of Entinostat in Combination with Pembrolizumab in Patients with Non-small Cell Lung Cancer, with Expansion Cohorts in Patients with Non-small Cell Lung Cancer, Melanoma, and Mismatch Repair-Proficient Colorectal Cancer

Physician & Study Coordinator

Physician

Sanjiv Agarwala, MD

Sanjiv Agarwala, MD

Study Coordinator

Vanessa Shaw, BS, RN
484-526-6038

Vanessa.Shaw@sluhn.org

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Synopsis

Treatment Agent: Pembrolizumab and Entinostat

Synopsis:  The purpose of this study is to find out what the best dose of entinostat is when taking both entinostat and pembrolizumab together, as well as to see if there are side effects when the two drugs are combined. This study will also look at whether the combination of these two drugs may slow the progression of cancer. It will also study whether there is something in the blood that can be measured to assess how the therapy works with the patient’s immune system and/or in being able to predict how well future patients may respond to the therapy.

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Inclusion Criteria

Patients with NSCLC:

  • Has histologically- or pathologically-confirmed recurrent/metastatic NSCLC.
  • If has adenocarcinoma, required to have previously been tested for anaplastic lymphoma kinase (ALK) rearrangements and epidermal growth factor receptor (EGFR) mutations, with results available for collection in this study, and, if positive, has been treated with prior EGFR or ALK therapy.
  • Received at least 1 chemotherapeutic regimen in the advanced/metastatic setting and experienced documented, unequivocal progressive disease by either RECIST 1.1 or clinical assessment.
  • Patients with NSCLC enrolled in Cohort 1 of the Expansion Phase should not have been previously treated with a PD-1/PD-L1-blocking antibody

Patients in Expansion Phase, Cohorts 2 and 3:

  • Previously treated with a PD-1/PD-L1-blocking antibody and experienced experienced documented, unequivocal progressive disease by irRECIST during or after such treatment.

Patients with Melanoma:

  • Has a histologically- or cytologically-confirmed diagnosis of unresectable or metastatic melanoma and experienced unequivocal progressive disease following a PD-1 or PD-L1-blocking antibody and, if BRAF V600 mutation-positive, a BRAF inhibitor.

Patients in Expansion Phase, Cohort 4 (Colorectal Cancer)

Received at least 1 chemotherapeutic regimen in the advanced/metastatic setting and experienced documented, unequivocal progressive disease by either RECIST 1.1 or clinical assessment. Must have documented mismatch repair-proficient colon cancer as determined by either immunohistochemistry for mismatch repair proteins or PCR-based functional microsatellite instability. Patients with colorectal cancer enrolled in Cohort 4 should not have been previously treated with a PD-1/PD-L1-blocking antibody

All Patients :

  • Aged 18 years or older on the day written informed consent is given.
  • If has brain metastases, must have stable neurologic status following local therapy for at least 4 weeks without the use of steroids or on stable or decreasing dose of ≤10 mg daily prednisone (or equivalent), and must be without neurologic dysfunction that would confound the evaluation of neurologic and other AEs.
  • Evidence of locally recurrent or metastatic disease based on imaging studies within 28 days before the first study drug dose:
    • At least 1 measurable lesion ≥20 mm by conventional techniques or ≥10 mm by spiral CT scan or MRI, with the last imaging performed within 28 days before the first study drug dose. If there is only 1 measurable lesion and it is located in previously irradiated field, it must have demonstrated unequivocal progression according to RECIST, version 1.1.
  • If receiving radiation therapy, has a 2-week washout period following completion of the treatment prior to receiving the first study drug dose and continues to have at least 1 measureable lesion, per above criterion.
  • ECOG performance status of 0 or 1.
  • Has acceptable, applicable laboratory parameters.
  • Female subjects must not be pregnant.
  • If male, agrees to use an adequate method of contraception
  • Experienced resolution of toxic effect(s) of the most recent prior chemotherapy to Grade 1 or less (except alopecia). If patient underwent major surgery or radiation therapy of >30 Gy, they must have recovered from the toxicity and/or complications from the intervention.
  • Willing to have fresh tumor samples collected during screening and at other time points designated as mandatory, per the Schedule of Study Assessments.
  • Able to understand and give written informed consent and comply with study procedures.

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Exclusion Criteria

Patients meeting any of the following criteria are not eligible for study participation:

  • Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
  • Active autoimmune disease that has required systemic treatment in past 2 years (i.e., with disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
  • History of interstitial lung disease (ILD).
  • Allergy to benzamide or inactive components of entinostat.
  • History of allergies to any active or inactive ingredients of pembrolizumab.
  • History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator, including, but not limited to:
    • Myocardial infarction or arterial thromboembolic events within 6 months prior to baseline or severe or unstable angina, New York Heart Association (NYHA) Class III or IV disease, or a QTc interval > 470 msec.
    • Uncontrolled heart failure or hypertension, uncontrolled diabetes mellitus, or uncontrolled systemic infection.
    • Another known additional malignancy that is progressing or requires active treatment (excluding adequately treated basal cell carcinoma or cervical intraepithelial neoplasia [CIN]/cervical carcinoma in situ or melanoma in situ). Prior history of other cancer is allowed, as long as there is no active disease within the prior 5 years.
    • Evidence of pneumonitis or history of pneumonitis.
    • Active infection requiring systemic therapy.
    • Known active central nervous system (CNS) metastases and/or carcinomatous meningitis.

Note: Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging [using the identical imaging modality for each assessment, either MRI or CT scan] for at least 4 weeks prior to the first dose of study drug and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 2 weeks prior to the first dose of study drug or are on stable or decreasing dose of ≤10 mg daily prednisone (or equivalent). This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.

  • Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
  • Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
  • Received a live virus vaccination within 30 days of the first dose of treatment.
  • Prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to baseline or who has not recovered (i.e., ≤Grade 1 or at baseline) from AEs due to agents administered more than 4 weeks earlier.
  • Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study baseline or who has not recovered (i.e., ≤Grade 1 or at baseline) from AEs due to a previously administered agent.

Note: Patients with ≤Grade 2 neuropathy or ≤Grade 2 alopecia are an exception to this criterion and may qualify for the study.

Note: If patient underwent major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.

  • Received transfusion of blood products (including platelets or red blood cells) or administration of colony stimulating factors (including granulocyte-colony stimulating factor [G-CSF], granulocyte macrophage-colony stimulating factor [GM-CSF], or recombinant erythropoietin) within 4 weeks prior to the first dose of study drug.
  • Currently receiving treatment with any other agent listed on the prohibited medication list such as valproic acid, or other systemic cancer agents within 14 days of the first dose of treatment.
  • If female, is pregnant, breastfeeding, or expecting to conceive, or if male, expect to father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study drug.
  • Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies).
  • Known active hepatitis B (e.g., hepatitis B surface antigen-reactive) or hepatitis C (e.g., hepatitis C virus ribonucleic acid [qualitative]).
  • For CRC expansion cohort, prior history of malignant bowel obstruction requiring hospitalization in the 6 months prior to enrollment.
  • For the CRC expansion, history of uncontrolled ascites, defined as symptomatic ascites and/or repeated paracenteses for symptom control in the past 3 months.

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NRG-GI004

Colorectal Cancer Metastatic dMMR Immuno-Therapy (COMMIT) Study: A Randomized Phase III Study of mFOLFOX6/Bevacizumab Combination Chemotherapy with or Without Atezolizumab or Atezolizumab Monotherapy in the First-Line Treatment of Patients with Deficient DNA Mismatch Repair (dMMR) Metastatic Colorectal Cancer

Physician & Study Coordinator

Physician

Sanjiv Agarwala, MD

Asim Ali, MD

Study Coordinator

Jessicca Rosario, BS
484-526-7952

Jessicca.rosario@sluhn.org

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Synopsis

Treatment Agent: Atezolizumab

Synopsis: The purpose of this study is to learn if adding an experimental drug, atezolizumab (MPDL3280A), to a usual treatment or giving the experimental drug alone is better than the usual treatment alone. The usual treatment in this study is the chemotherapy drugs,
5-flouorouracil (5-FU), leucovorin, and oxaliplatin. This combination is called FOLFOX.  In addition to FOLFOX, bevacizumab will be given.  Bevacizumab is in a group of drugs called biologic therapy.  FOLFOX and bevacizumab are approved by the FDA to treat metastatic CRC. To be better than FOLFOX and bevacizumab, atezolizumab given with FOLFOX and bevacizumab or atezolizumab given alone should keep your cancer from growing for more than 7 months.


Another purpose of this study is to test the good and bad effects of atezolizumab when added to the usual treatment and when given alone.  Atezolizumab may keep your cancer from growing but it can also cause side effects.  Atezolizumab is FDA-approved for treating metastatic cancers of the bladder and lung. Atezolizumab is considered experimental in this study because it is not approved to treat metastatic CRC.

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Inclusion Criteria

Patients with NSCLC:

  • Has histologically- or pathologically-confirmed recurrent/metastatic NSCLC.
  • If has adenocarcinoma, required to have previously been tested for anaplastic lymphoma kinase (ALK) rearrangements and epidermal growth factor receptor (EGFR) mutations, with results available for collection in this study, and, if positive, has been treated with prior EGFR or ALK therapy.
  • Received at least 1 chemotherapeutic regimen in the advanced/metastatic setting and experienced documented, unequivocal progressive disease by either RECIST 1.1 or clinical assessment.
  • Patients with NSCLC enrolled in Cohort 1 of the Expansion Phase should not have been previously treated with a PD-1/PD-L1-blocking antibody

Patients in Expansion Phase, Cohorts 2 and 3:

  • Previously treated with a PD-1/PD-L1-blocking antibody and experienced experienced documented, unequivocal progressive disease by irRECIST during or after such treatment.

Patients with Melanoma:

  • Has a histologically- or cytologically-confirmed diagnosis of unresectable or metastatic melanoma and experienced unequivocal progressive disease following a PD-1 or PD-L1-blocking antibody and, if BRAF V600 mutation-positive, a BRAF inhibitor.

Patients in Expansion Phase, Cohort 4 (Colorectal Cancer)

Received at least 1 chemotherapeutic regimen in the advanced/metastatic setting and experienced documented, unequivocal progressive disease by either RECIST 1.1 or clinical assessment. Must have documented mismatch repair-proficient colon cancer as determined by either immunohistochemistry for mismatch repair proteins or PCR-based functional microsatellite instability. Patients with colorectal cancer enrolled in Cohort 4 should not have been previously treated with a PD-1/PD-L1-blocking antibody

All Patients :

  • Aged 18 years or older on the day written informed consent is given.
  • If has brain metastases, must have stable neurologic status following local therapy for at least 4 weeks without the use of steroids or on stable or decreasing dose of ≤10 mg daily prednisone (or equivalent), and must be without neurologic dysfunction that would confound the evaluation of neurologic and other AEs.
  • Evidence of locally recurrent or metastatic disease based on imaging studies within 28 days before the first study drug dose:
    • At least 1 measurable lesion ≥20 mm by conventional techniques or ≥10 mm by spiral CT scan or MRI, with the last imaging performed within 28 days before the first study drug dose. If there is only 1 measurable lesion and it is located in previously irradiated field, it must have demonstrated unequivocal progression according to RECIST, version 1.1.
  • If receiving radiation therapy, has a 2-week washout period following completion of the treatment prior to receiving the first study drug dose and continues to have at least 1 measureable lesion, per above criterion.
  • ECOG performance status of 0 or 1.
  • Has acceptable, applicable laboratory parameters.
  • Female subjects must not be pregnant.
  • If male, agrees to use an adequate method of contraception
  • Experienced resolution of toxic effect(s) of the most recent prior chemotherapy to Grade 1 or less (except alopecia). If patient underwent major surgery or radiation therapy of >30 Gy, they must have recovered from the toxicity and/or complications from the intervention.
  • Willing to have fresh tumor samples collected during screening and at other time points designated as mandatory, per the Schedule of Study Assessments.
  • Able to understand and give written informed consent and comply with study procedures.

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Exclusion Criteria
  • Patients with central nervous system (CNS) metastases are excluded, with the following exceptions:
    • Patients with asymptomatic untreated CNS metastases may be enrolled, provided all eligibility criteria are met, as well as the following:
      • Evaluable or measurable disease outside the CNS
      • No metastases to brain stem, midbrain, pons, medulla, cerebellum, or within 10 mm of the optic apparatus (optic nerves and chiasm)
      • No history of intracranial hemorrhage or spinal cord hemorrhage
      • No ongoing requirement for dexamethasone for CNS disease; patients on a stable dose of anticonvulsants are permitted.
      • No neurosurgical resection or brain biopsy within 28 days prior to randomization
    • Patients with asymptomatic treated CNS metastases may be enrolled, provided all eligibility criteria are met, as well as the following:
      • Radiographic demonstration of improvement upon the completion of CNS-directed therapy and no evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study
      • No stereotactic radiation or whole-brain radiation within 28 days prior to randomization
      • Screening CNS radiographic study >= 28 days from completion of radiotherapy and >= 14 days from discontinuation of corticosteroids
  • Known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies, fluoropyrimidines, folic acid derivatives or oxaliplatin
  • Uncontrolled high blood pressure defined as systolic blood pressure (BP) > 150 mmHg or diastolic BP 90 mmHg with or without anti-hypertensive medication; patients with initial BP elevations are eligible if initiation or adjustment of BP medication lowers pressure to meet entry criteria
  • Any of the following cardiac conditions:
    • Documented New York Heart Association (NYHA) class III or IV congestive heart failure
    • Myocardial infarction within 6 months prior to randomization
    • Unstable angina within 6 months prior to randomization
    • Symptomatic arrhythmia
  • Serious or non-healing wound, skin ulcer, or bone fracture
  • History of transient ischemic attack (TIA), cerebrovascular accident (CVA), gastrointestinal (GI) perforation or arterial thrombotic event within 6 months prior to randomization or symptomatic peripheral ischemia
  • Other malignancies are excluded unless the patient has completed therapy for the malignancy >= 12 months prior to randomization and is considered disease-free; patients with the following cancers are eligible if diagnosed and treated within the past 12 months: in situ carcinomas or basal cell and squamous cell carcinoma of the skin
  • Known DPD (dihydro pyrimidine dehydrogenase) deficiency
  • Symptomatic peripheral sensory neuropathy >= grade 2 (Common Terminology Criteria for Adverse Events [CTCAE] version [v] 4.0) in patients with no prior oxaliplatin therapy
  • Prior treatment with oxaliplatin chemotherapy within 6 months prior to randomization
  • Prior treatment with anti-PD-1, or anti-PD-L1 therapeutic antibody or pathway-targeting agents; patients who have received prior treatment with anti-CTLA-4 may be enrolled provided the following requirements are met:
    • Minimum of 12 weeks from the first dose of anti-CTLA-4 and > 6 weeks from the last dose to randomization
    • No history of severe immune-related adverse effects (CTCAE Grade 3 and 4) from anti-CTLA-4
  • Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events (other than alopecia) due to agents administered more than 4 weeks earlier are excluded; however, the following therapies are allowed:
    • Hormone-replacement therapy or oral contraception
    • Herbal therapy > 7 days prior to randomization (herbal therapy intended as anticancer therapy must be discontinued at least 1 week prior to randomization)
    • Palliative radiotherapy for bone metastases > 14 days prior to randomization
  • Treatment with systemic immunostimulatory medications (including, but not limited to interferon [IFN]-alpha or interleukin [IL]-2 within 42 days prior to randomization
  • Treatment with systemic immunosuppressive medications (including, but not limited to, prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [anti-TNF] agents) within 14 days prior to randomization; however,
    • Patients who have received acute, low dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea; or chronic daily treatment with corticosteroids with a dose of =< 10 mg/day methylprednisolone equivalent) may be enrolled
    • The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed
  • Patients taking bisphosphonate therapy for symptomatic hypercalcemia; use of bisphosphonate therapy for other reasons (e.g., bone metastasis or osteoporosis) is allowed
  • Patients requiring treatment with a receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitor (e.g., denosumab) who cannot discontinue it before treatment with atezolizumab
  • Treatment with any other investigational agent within 4 weeks prior to randomization
  • Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease; however,
    • Patients with past or resolved hepatitis B infection (defined as having a negative hepatitis B surface antigen [HBsAg] test and a positive anti-HBc [antibody to hepatitis B core antigen] antibody test) are eligible
    • Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV ribonucleic acid (RNA)
  • History or risk of autoimmune disease, including, but not limited to, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's syndrome, Bell's palsy, Guillain-Barre syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis; however,
    • Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone may be eligible
    • Patients with controlled type 1 diabetes mellitus on a stable insulin regimen may be eligible
    • Patients with eczema, psoriasis, lichen simplex chronicus or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided that they meet the following conditions:
      • Patients with psoriasis must have a baseline ophthalmologic exam to rule out ocular manifestations
      • Rash must cover less than 10% of body surface area (BSA)
      • Disease is well controlled at baseline and only requiring low potency topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, fluocinolone 0.01%, desonide 0.05%, alclometasone dipropionate 0.05%)
      • No acute exacerbations of underlying condition within the last 12 months (not requiring psoralen plus ultraviolet A radiation [PUVA], methotrexate, retinoids, biologic agents, oral calcineurin inhibitors; high potency or oral steroids)
  • History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest computed tomography (CT) scan; history of radiation pneumonitis in the radiation field (fibrosis) is permitted
  • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
  • Patients with known active tuberculosis (TB) are excluded
  • Severe infections within 28 days prior to randomization, including but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
  • Signs or symptoms of infection within 14 days prior to randomization
  • Received oral or intravenous (IV) antibiotics within 14 days prior to randomization; patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible
  • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to randomization or anticipation of need for a major surgical procedure during the course of the study
  • Administration of a live, attenuated vaccine within 28 days prior to randomization or anticipation that such a live, attenuated vaccine will be required during the study and up to 5 months after the last dose of atezolizumab; Note: influenza vaccination should be given during influenza season only (approximately October to March); patients must not receive live, attenuated influenza vaccine within 28 days prior to randomization or at any time during the study
  • Psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with atezolizumab; (Note: pregnancy testing should be performed within 14 days prior to randomization according to institutional standards for women of childbearing potential)
  • Patients positive for human immunodeficiency virus (HIV) are NOT excluded from this study, but HIV-positive patients must have:
    • A stable regimen of highly active anti-retroviral therapy (HAART); and
    • No requirement for concurrent antibiotics or antifungal agents for the prevention of opportunistic infections; and
    • A CD4 count above 250 cells/uL and an undetectable HIV viral load on standard PCR-based tests
  • Patients with prior allogeneic bone marrow transplantation or prior solid organ transplantation

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ECOG-ACRIN EA2165

A Randomized Phase II Study of Nivolumab After Combined Modality Therapy (CMT) in High Risk Anal Cancer

Physician & Study Coordinator

Physician

Sanjiv Agarwala, MD

Asim Ali, MD

Study Coordinator

Jessicca Rosario, BS
484-526-7952

Jessicca.rosario@sluhn.org

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Synopsis

Treatment Agent: Nivolumab

Synopsis: The purpose of this study is to find if adding the study drug, nivolumab (also known as OPDIVO®), after standard chemotherapy {(mitomycin-C and 5-fluorouracil (5-FU) or capecitabine) or 5-FU and cisplatin} and radiation will prevent the anal cancer from returning. Nivolumab is a drug that may turn on the body’s immune system to attack any cancer cells that may remain after chemotherapy and radiation. The addition of nivolumab may help prevent your cancer from returning, but it could also cause side effects. This research study will allow researchers to find out whether this different treatment is better, the same, or worse than the usual treatment for anal cancer. The use of nivolumab in this study is investigational (not approved by the FDA) in your type of cancer.

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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
  • 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 not have received less than 54 Gy of radiation for the treatment of the anal cancer
  • Patients must have 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 ANC level must be > 1500/mm^3 within 2 weeks prior to registration
  • Serum creatinine must be =< 2 X ULN within 2 weeks prior to registration
  • Total bilirubin must be < 2 X ULN within 2 weeks prior to registration
  • AST (SGOT)/ALT (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 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)
  • Scans done within 4 weeks of randomization to Step 2
  • Patient must have recovered from all toxicities associated with chemoradiotherapy for anal cancer, to grade =< 1 with the exception of alopecia
  • Patient must start treatment within 12 weeks of completion of chemoradiotherapy
  • 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 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
  • 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 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
  • 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
  • Patients must not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to nivolumab

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