Clinical Trials /

Nivolumab With or Without Ipilimumab in Treating Patients With Refractory Metastatic Anal Canal Cancer

NCT02314169

Description:

This phase II trial studies how well nivolumab with or without ipilimumab works in treating patients with anal canal cancer that has not responded to previous treatment (refractory) and has spread to other places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Related Conditions:
  • Anal Canal Squamous Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Nivolumab in Treating Patients With Refractory Metastatic Anal Canal Cancer
  • Official Title: A Multi-Institutional Phase 2 Study of Nivolumab in Refractory Metastatic Squamous Cell Carcinoma of the Anal Canal

Clinical Trial IDs

  • ORG STUDY ID: NCI-2014-02420
  • SECONDARY ID: NCI-2014-02420
  • SECONDARY ID: NCI9673
  • SECONDARY ID: P9673_R03PAPPHOLD01
  • SECONDARY ID: 9673
  • SECONDARY ID: 9673
  • SECONDARY ID: N01CM00032
  • SECONDARY ID: N01CM00038
  • SECONDARY ID: N01CM00039
  • SECONDARY ID: N01CM00071
  • SECONDARY ID: N01CM00099
  • SECONDARY ID: N01CM00100
  • SECONDARY ID: P30CA016672
  • SECONDARY ID: UM1CA186704
  • SECONDARY ID: UM1CA186712
  • SECONDARY ID: UM1CA186716
  • NCT ID: NCT02314169

Conditions

  • Anal Canal Squamous Cell Carcinoma
  • Metastatic Anal Canal Carcinoma
  • Recurrent Anal Canal Carcinoma
  • Stage IV Anal Canal Cancer AJCC v6 and v7

Interventions

DrugSynonymsArms
NivolumabBMS-936558, MDX-1106, NIVO, ONO-4538, OpdivoTreatment (nivolumab)

Purpose

This phase II trial studies how well nivolumab works in treating patients with anal canal cancer that has not responded to previous treatment (refractory) and has spread to other places in the body (metastatic). Monoclonal antibodies, such as nivolumab, may block tumor growth in different ways by targeting certain cells.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To evaluate overall response rate (ORR) with nivolumab in patients with previously treated
      metastatic squamous cell carcinoma (SCCA) of the anal canal.

      SECONDARY OBJECTIVES:

      I. To evaluate progression-free survival (PFS) of nivolumab in patients with previously
      treated metastatic SCCA of the anal canal.

      II. To evaluate overall survival (OS) in patients with previously treated metastatic SCCA of
      the anal canal treated with nivolumab.

      III. To evaluate the grade 3 and 4 toxicity rate in patients with previously treated
      metastatic SCCA of the anal canal when treated with nivolumab.

      TERTIARY OBJECTIVES:

      I. To evaluate ORR, PFS, and OS based on expression of programmed cell death 1 ligand 1
      (PD-L1), programmed cell death 1 (PD-1), peritumoral cluster of differentiation (CD)8+ tumor
      infiltrating lymphocytes (TILs), peritumoral CD4+ TILs, and regulatory T cells as analyzed
      from tumor biopsies in previously treated patients with metastatic SCCA of the anal canal
      when treated with nivolumab.

      II. To evaluate radiographic responses according to relative changes in proportions of
      anti-human papillomavirus (HPV) specific CD8+ and CD4+ TILs and regulatory T cells in
      patients with previously treated metastatic SCCA of the anal canal following treatment with
      nivolumab, analyzed from serial peripheral blood samples.

      OUTLINE:

      Patients receive nivolumab intravenously (IV) over approximately 60 minutes once every two
      weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up for 100 days and then every 3
      months for 2 years.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (nivolumab)ExperimentalPatients receive nivolumab IV over approximately 60 minutes once every two weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Patients must have histologically or cytologically confirmed previously treated
                 metastatic squamous cell carcinoma of the anal canal
    
              -  Patients must have measurable disease according to the standard Response Evaluation
                 Criteria in Solid Tumors (RECIST) version 1.1, computed tomography (CT) scans or
                 magnetic resonance imagings (MRIs) used to assess the measurable disease must have
                 been completed within 28 days prior to study drug initiation
    
              -  Patients must have been treated with at least one prior systemic treatment for
                 incurable advanced or metastatic SCCA of the anal canal; prior treatment for
                 metastatic disease is not required for patients who develop new metastatic lesions
                 during or within 6 months of completion of chemoradiation for limited-stage disease;
                 patients who receive chemotherapy for incurable advanced or metastatic SCCA of the
                 anal canal must wait a minimum >= 28 days (6 weeks for nitrosoureas or mitomycin C)
                 after the date of completion of chemotherapy prior to initiating treatment with
                 nivolumab on this study; patients who undergo radiotherapy to a site of tumor must
                 wait a minimum >= 3 months from the date of completion of radiotherapy prior to
                 initiating treatment with nivolumab on this study
    
              -  Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 (Karnofsky >= 80%)
    
              -  Leukocytes >= 2,000/mcL
    
              -  Absolute neutrophil count >= 1,500/mcL
    
              -  Hemoglobin >= 9.0 gm/dL
    
              -  Platelets >= 100,000/mcL
    
              -  Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (except patients
                 with Gilbert syndrome, who can have total bilirubin < 3.0 mg/dL)
    
              -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
                 [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
                 =< 2.5 x ULN
    
              -  Serum creatinine =< 1.5 x ULN OR creatinine clearance (CrCl) >= 50 mL/min (if using
                 the Cockcroft-Gault formula)
    
              -  Women of child-bearing potential (WOCBP) and men must agree to use adequate
                 contraception (hormonal or barrier method of birth control; abstinence) prior to study
                 entry and for the duration of study participation; women of childbearing potential
                 must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or
                 equivalent units of human chorionic gonadotropin [HCG]) within 24 hours prior to the
                 start of nivolumab; women must not be breastfeeding; women who are not of childbearing
                 potential (i.e., who are postmenopausal or surgically sterile as well as azoospermic
                 men) do not require contraception
    
              -  Women of childbearing potential (WOCBP) is defined as any female who has experienced
                 menarche and who has not undergone surgical sterilization (hysterectomy or bilateral
                 oophorectomy) or who is not postmenopausal; menopause is defined clinically as 12
                 months of amenorrhea in a woman over 45 in the absence of other biological or
                 physiological causes
    
              -  WOCBP receiving nivolumab will be instructed to adhere to contraception for a period
                 of 23 weeks after the last dose of investigational product; men receiving nivolumab
                 and who are sexually active with WOCBP will be instructed to adhere to contraception
                 for a period of 31 weeks after the last dose of investigational product
    
              -  Should a woman become pregnant or suspect she is pregnant while she or her partner is
                 participating in this study, she (or the participating partner) should inform the
                 treating physician immediately
    
              -  Ability to understand and the willingness to sign a written informed consent document
    
              -  Brain metastases are allowed if they have been adequately treated with radiotherapy or
                 surgery and have been stable for at least three months prior to registration; eligible
                 subjects should be neurologically asymptomatic; there is no magnetic resonance imaging
                 (MRI) evidence of progression for a minimum of 4 weeks after treatment is complete and
                 within 28 days prior to the first dose of nivolumab administration; there must also be
                 no requirement for immunosuppressive doses of systemic corticosteroids (> 10 mg/day
                 prednisone equivalents) for at least 2 weeks prior to study drug administration
    
              -  All patients must be willing to undergo testing for human immunodeficiency virus (HIV)
                 testing if not tested within the past 6 months
    
              -  If HIV+ positive, all patients infected with human immunodeficiency virus (HIV) may be
                 eligible for study provided that their CD4+ count >= 300/uL; their viral load is
                 undetectable; they are currently receiving highly active antiretroviral therapy
                 (HAART)
    
              -  All HIV+ patients will be under the care of an infectious diseases specialist; if a
                 relationship with an infectious diseases specialist is not established, infectious
                 disease specialist will be consulted; records of all viral counts and peripheral
                 T-cell counts must be sent to the study coordinator in order to follow these values
                 over the course of treatment
    
              -  All patients must be willing to be tested for hepatitis screening; patients
                 co-infected with hepatitis B virus and/or hepatitis C virus may be included in this
                 study provided that their liver function tests remain within the limits listed above;
                 patients must be followed by a hepatologist during the course of this study
    
            Exclusion Criteria:
    
              -  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 (AEs) due to agents administered more than 4 weeks
                 earlier (i.e., grade >= 2 AE present); palliative (limited-field) radiation therapy is
                 permitted, as long as the lesion being considered for palliative radiation is not a
                 target lesion
    
              -  Patients who are receiving any other investigational agents
    
              -  Patients should be excluded if they have had prior treatment with an anti-PD-1,
                 anti-PD-L1, anti-programmed cell death ligand 2 (PD-L2), anti-cytotoxic
                 T-lymphocyte-associated protein 4 (CTLA-4) antibody, or any other antibody or drug
                 specifically targeting T-cell co-stimulation or immune checkpoint pathways
    
              -  History of allergic reactions attributed to compounds of similar chemical or biologic
                 composition to nivolumab
    
              -  History of severe hypersensitivity reaction to any monoclonal antibody
    
              -  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
    
              -  Patients with active autoimmune disease or history of autoimmune disease that might
                 recur, which may affect vital organ function or require immune suppressive treatment
                 including chronic prolonged systemic corticosteroids (defined as corticosteroid use of
                 duration one month or greater), should be excluded; these include but are not limited
                 to patients with a history of immune related neurologic disease, multiple sclerosis,
                 autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis;
                 systemic autoimmune disease such as systemic lupus erythematosus (SLE), connective
                 tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative
                 colitis, and patients with a history of toxic epidermal necrolysis (TEN),
                 Stevens-Johnson syndrome, or anti-phospholipid syndrome should be excluded
    
              -  Patients should be excluded if they have a condition requiring systemic treatment with
                 either corticosteroids (> 10 mg daily prednisone equivalents) or other
                 immunosuppressive medications within 14 days of study drug administration; inhaled or
                 topical steroids and adrenal replacement doses =< 10 mg daily prednisone equivalents
                 are permitted in the absence of active autoimmune disease; patients are permitted to
                 use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids
                 (with minimal systemic absorption); physiologic replacement doses of systemic
                 corticosteroids are permitted, even if =< 10 mg/day prednisone equivalents; a brief
                 course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for
                 treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction
                 caused by contact allergen) is permitted
    
              -  No other prior malignancy is allowed except for the following: adequately treated
                 basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated
                 stage I or II cancer from which the patient is currently in complete remission, or any
                 other cancer from which the patient has been disease free for at least three years
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Overall Response Rate: Number of Participants With Response
    Time Frame:Up to 2 years
    Safety Issue:
    Description:Responses assessed using computed tomography (CT) scans or magnetic resonance imaging according to standard Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria in order to assess disease progression. Complete Response (CR): Disappearance all target lesions; any pathological lymph nodes reduction in short axis to < 10 mm (< 1 cm). Partial Response (PR): > 30% decrease in sum diameters of target lesions. Progressive Disease (PD): > 20% increase in sum diameters lesions. (Note: appearance of one or > new lesions considered progressions). Stable Disease (SD): Neither shrinkage qualify for PR nor increase for PD.

    Secondary Outcome Measures

    Measure:Number of Participants With Toxicities Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0
    Time Frame:Up to 100 days post-treatment
    Safety Issue:
    Description:The most frequent of adverse events measured relative to the total number of patients treated, and the toxicities tabulated by grade according to CTCAE.
    Measure:Overall Survival
    Time Frame:From initiation of treatment with nivolumab until death, assessed up to 2 years
    Safety Issue:
    Description:Time measured from initiation of treatment with nivolumab till death. Kaplan-Meier analysis will be performed to estimate the median overall survival with a 95% confidence interval.
    Measure:Progression-free Survival
    Time Frame:From initiation of treatment with nivolumab until the time of disease progression, assessed up to 2 years
    Safety Issue:
    Description:From initiation of treatment with nivolumab until the time of disease progression, time measured in months. Kaplan-Meier analysis performed to estimate the median progression-free survival with a 90% confidence interval.

    Details

    Phase:Phase 2
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:National Cancer Institute (NCI)

    Last Updated