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

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ClinicalTrials.gov Identifier: NCT03233711
Recruitment Status : Recruiting
First Posted : July 31, 2017
Last Update Posted : December 14, 2018
Sponsor:
Collaborator:
Canadian Cancer Trials Group
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Anal Basaloid Carcinoma Anal Canal Cloacogenic Carcinoma Anal Margin Squamous Cell Carcinoma Stage II Anal Canal Cancer AJCC v6 and v7 Stage IIB Anal Cancer AJCC v8 Stage III Anal Canal Cancer AJCC v6 and v7 Stage IIIA Anal Canal Cancer AJCC v6 and v7 Stage IIIB Anal Canal Cancer AJCC v6 and v7 Biological: Nivolumab Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

I. 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:

I. To compare nivolumab following combined modality therapy (CMT) with observation in patients with high risk anal carcinoma with regard to objective response rate (complete [CR] and partial [PR]), stable disease and progression.

II. To compare nivolumab following combined modality therapy (CMT) with observation in patients with high risk anal carcinoma with regard to severe toxicity interval.

III. To compare nivolumab following combined modality therapy (CMT) with observation in patients with high risk anal carcinoma with regard to colostomy-free survival.

IV. To compare nivolumab following combined modality therapy (CMT) with observation in patients with high risk anal carcinoma with regard to overall survival.

V. To compare nivolumab following combined modality therapy (CMT) with observation in patients with high risk anal carcinoma with regard to toxicity.

OUTLINE: Patients who received standard CMT are randomized to 1 of 2 arms.

ARM A: Patients receive nivolumab intravenously (IV) over 30 minutes on day 1. Treatment repeats every 14 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

ARM B: Patients undergo observation.

After completion of study treatment, patients are followed up every 3 months for 2 years, then every 6 months for 3 years.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Phase II Study of Nivolumab After Combined Modality Therapy (CMT) in High Risk Anal Cancer
Actual Study Start Date : April 13, 2018
Estimated Primary Completion Date : December 30, 2019
Estimated Study Completion Date : December 30, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Anal Cancer
Drug Information available for: Nivolumab

Arm Intervention/treatment
Experimental: Arm A (nivolumab)
Patients receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 14 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Biological: Nivolumab
Given IV
Other Names:
  • BMS-936558
  • MDX-1106
  • NIVO
  • ONO-4538
  • Opdivo

No Intervention: Arm B (clinical observation)
Patients undergo observation.



Primary Outcome Measures :
  1. Disease free survival [ Time Frame: Up to 5 years ]
    Will be defined as the occurrence of progression of local disease, distant metastases, second primary or death from the date of randomization.


Secondary Outcome Measures :
  1. Objective response rate [ Time Frame: Up to 5 years ]
    Will be defined by complete and partial response.

  2. Severe toxicity interval [ Time Frame: The time between randomization and the occurrence of late severe side effects (up to 5 years) ]
    The following late side effects are considered as severe: any anal/rectal damage (ulcer, fistula, or perforation), rectal stenosis that required colostomy, skin ulceration, and severe fibrosis. This parameter estimates the probability of being free of late side effects for patients under loco-regional control.

  3. Colostomy-free survival [ Time Frame: Up to 5 years ]
  4. Overall survival [ Time Frame: Up to 5 years ]
  5. Incidence of toxicities [ Time Frame: Up to 5 years ]
    Will be assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03233711


  Show 533 Study Locations
Sponsors and Collaborators
National Cancer Institute (NCI)
Canadian Cancer Trials Group
Investigators
Principal Investigator: Lakshmi Rajdev ECOG-ACRIN Cancer Research Group

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT03233711     History of Changes
Other Study ID Numbers: NCI-2017-01347
NCI-2017-01347 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
EA2165 ( Other Identifier: ECOG-ACRIN Cancer Research Group )
EA2165 ( Other Identifier: CTEP )
U10CA180820 ( U.S. NIH Grant/Contract )
First Posted: July 31, 2017    Key Record Dates
Last Update Posted: December 14, 2018
Last Verified: October 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Squamous Cell
Anus Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Anus Diseases
Rectal Diseases
Nivolumab
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs