Clinical Trials /

Adjuvant Avelumab in Merkel Cell Cancer

NCT03271372

Description:

This randomized phase III trial studies how well avelumab works in treating patients with Merkel cell cancer that has spread to the lymph nodes and have undergone surgery and/or radiation therapy. Immunotherapy with monoclonal antibodies, such as avelumab, 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:
  • Merkel Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Adjuvant Avelumab in Merkel Cell Cancer
  • Official Title: A Multicenter, Randomized, Double-Blinded, Placebo-Controlled, Phase 3 Trial of Adjuvant Avelumab (Anti-PDL-1 Antibody) in Merkel Cell Carcinoma Patients With Clinically Detected Lymph Node Metastases

Clinical Trial IDs

  • ORG STUDY ID: 9820
  • SECONDARY ID: NCI-2017-00998
  • SECONDARY ID: RG1717054
  • SECONDARY ID: P30CA015704
  • NCT ID: NCT03271372

Conditions

  • Stage III Merkel Cell Carcinoma AJCC v7
  • Stage IIIB Merkel Cell Carcinoma AJCC v7

Interventions

DrugSynonymsArms
AvelumabBavencio, MSB-0010718C, MSB0010718CArm I (avelumab)

Purpose

This randomized phase III trial studies how well avelumab works in treating patients with Merkel cell cancer that has spread to the lymph nodes and have undergone surgery with or without radiation therapy. Monoclonal antibodies, such as avelumab, may stimulate the immune system and interfere with the ability of tumor cells to grow and spread.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To compare the clinical activity of adjuvant avelumab to that of placebo, as determined by
      relapse-free survival in subjects with clinically detected nodal metastases from Merkel cell
      carcinoma (MCC) after definitive therapy (surgery with/without adjuvant radiation therapy
      [RT]).

      SECONDARY OBJECTIVES:

      I. To examine whether post-operative adjuvant therapy with avelumab improves overall survival
      (OS) as compared to placebo.

      II. To examine whether post-operative adjuvant therapy with avelumab improves distant
      metastases-free survival (DMFS) as compared to placebo.

      III. To assess whether post-operative adjuvant therapy with avelumab improves
      disease-specific survival (DSS) as compared to placebo.

      IV. To assess the safety and tolerability of avelumab in the adjuvant setting.

      TERTIARY OBJECTIVES:

      I. To explore predictive biomarkers in tissue and peripheral blood for immunogenicity of
      avelumab.

      OUTLINE: Patients are randomized to 1 of 2 arms.

      ARM I: Patients receive avelumab intravenously (IV) over 1 hour once every 15 days for the
      first 120 days (Induction Phase 1), once every 30 days for the next 120 days (Induction Phase
      2), and then once every 120 days (Maintenance Phase) for a maximum of 720 days (approximately
      24 months or 2 years total) in the absence of disease progression or unacceptable toxicity.

      ARM II: Patients receive placebo IV over 1 hour once every 15 days for the first 120 days
      (Induction Phase 1), once every 30 days for the next 120 days (Induction Phase 2), and then
      once every 120 days (Maintenance Phase) for a maximum of 720 days (approximately 24 months or
      2 years total) in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up every 6 months for 3 years for
      a minimum of 5 years from study treatment initiation.
    

Trial Arms

NameTypeDescriptionInterventions
Arm I (avelumab)ExperimentalPatients receive avelumab IV over 1 hour once every 15 days for the first 120 days (Induction Phase 1), once every 30 days for the next 120 days (Induction Phase 2), and then once every 120 days (Maintenance Phase) for a maximum of 720 days (approximately 24 months or 2 years total) in the absence of disease progression or unacceptable toxicity.
  • Avelumab
Arm II (placebo)Placebo ComparatorPatients receive placebo IV over 1 hour once every 15 days for the first 120 days (Induction Phase 1), once every 30 days for the next 120 days (Induction Phase 2), and then once every 120 days (Maintenance Phase) for a maximum of 720 days (approximately 24 months or 2 years total) in the absence of disease progression or unacceptable toxicity.

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Histologically confirmed MCC metastases in clinically detected lymph node(s)
    
                   -  Confirmation of the MCC diagnosis in the clinically suspicious lymph node(s) is
                      mandatory for trial participation
    
                   -  Subjects must have had clinically-detected (i.e. either palpable or
                      radiologically abnormal) lymph nodal metastasis
    
                   -  (NOTE: In-transit metastases without regional nodal involvement could be allowed,
                      but only after written approval of the medical monitor)
    
              -  Must have completed definitive treatment that included surgical removal of the
                 clinically detected MCC metastases (with/without adjuvant radiation therapy as
                 determined by the treating investigator)
    
              -  Estimated life expectancy greater than 3 years
    
              -  Must start the study treatment no more than 60 days from the last dose of RT (if
                 administered) and no more than 120 days from the date of surgical removal of nodal
                 metastases
    
              -  Eastern Co-Operative Group (Eastern Cooperative Oncology Group [ECOG]) performance
                 score of 0 or 1
    
              -  Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
    
              -  Platelet count >= 100 x 10^9/L
    
              -  Hemoglobin >= 9 g/dL (may have been transfused)
    
              -  Total bilirubin level =< 1.5 x the upper limit of normal (ULN) range
    
              -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels =< 2.5 x
                 ULN
    
              -  Estimated creatinine clearance >= 30 mL/min according to the Cockcroft-Gault formula
                 or by 24-hour urine collection for creatinine clearance or according to local
                 institutional standard
    
              -  Women of childbearing potential must have a negative serum or urine pregnancy test at
                 screening
    
              -  Both male and female subjects must be willing to use highly effective contraception
                 (that is, methods with a failure rate of less than 1% per year) throughout the study
                 and for at least 30 days after last avelumab treatment administration if the risk of
                 conception exists
    
                   -  (NOTE: Women of childbearing potential and men must agree to use highly effective
                      contraception, as stipulated in national or local guidelines; should a woman
                      become pregnant or suspect she is pregnant while she or her partner is
                      participating in this study, the treating physician should be informed
                      immediately)
    
              -  Must have an ability to understand and the willingness to sign a written informed
                 consent document
    
              -  Must consent to allow the acquisition of existing formalin-fixed paraffin-embedded
                 (FFPE) tumor tissue, either a block or unstained slides, for performance of
                 correlative studies
    
            Exclusion Criteria:
    
              -  Clinical or radiologic suspicion of residual MCC at the time of enrollment
    
              -  Suspicion or known history of distant metastatic MCC, which is not classifiable as
                 local recurrence or regional metastasis
    
                   -  (NOTE: Patients presenting with nodal metastases in one lymph node basin and no
                      known primary tumor are allowed to enroll)
    
              -  Any prior systemic therapy (e.g. adjuvant, neo-adjuvant or concurrent use of
                 chemotherapy, immunotherapy or an investigational agent) for MCC at any time
    
              -  Any prior intra-lesional MCC therapy within 180 days from day 1 of study treatment
    
              -  Residual toxicity from prior therapy grade > 1 (National Cancer Institute [NCI]-Common
                 Terminology Criteria for Adverse Events [CTCAE] version [v] 4.0) that could interfere
                 with study endpoints or put patient safety at risk
    
              -  Previous malignant disease (other than Merkel cell carcinoma) diagnosed within 3 years
                 from day 1 of study treatment that could interfere with study endpoints or put patient
                 safety at risk
    
                   -  (NOTE: Exception will be made for adequately treated basal or squamous cell
                      carcinoma of the skin or carcinoma in situ [skin, bladder, cervical, colorectal,
                      breast] or low grade prostatic intraepithelial neoplasia or grade 1 prostate
                      cancer; any other neoplasm, which is adjudged by the treating investigator to
                      have a low risk of recurrence during the study, could be enrolled only after
                      written approval from the medical monitor)
    
              -  Use of any systemic immunosuppressive treatments including corticosteroids,
                 cyclosporine, mycophenolate mofetil et cetera, ongoing or within the last 3 months
                 prior to day 1 of treatment
    
                   -  (NOTE: Patients on physiologic dose of corticosteroids [=< 10 mg/day of
                      prednisone or equivalent] for long-term hormone-replacement therapy or those
                      requiring short, intermittent courses of corticosteroids for hypersensitivity
                      prophylaxis [such as for iodinated computed tomography (CT) contrast prophylaxis]
                      or those using intranasal, inhaled, topical steroids, or local steroid injection
                      [e.g., intra-articular injection] can be allowed)
    
              -  Immunosuppressed status due to known human immunodeficiency virus (HIV) infection,
                 severe uncontrolled diabetes, concurrent hematological malignancy, or other
                 comorbidities
    
              -  Uncontrolled intercurrent illness including, but not limited to, active serious
                 infection, active hepatitis B or hepatitis C infection, uncontrolled seizure disorder,
                 substance abuse disorder, or psychiatric illness/social situations that would limit
                 compliance with study requirements or would put the patient at increased risk of
                 complications during the study period
    
              -  Clinically significant (i.e., active) cardiovascular disease: cerebral vascular
                 accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months
                 prior to enrollment), unstable angina, congestive heart failure (>= New York Heart
                 Association Classification Class II), or serious cardiac arrhythmia requiring
                 medication
    
              -  Active or history of any serious autoimmune disease, prior organ transplantation,
                 including allogeneic stem-cell transplantation or immune-deficiencies that required
                 treatment with systemic immunosuppressive drugs and could flare-up during study
                 treatment
    
                   -  (NOTE: Patients with diabetes type I, vitiligo, psoriasis, or hypo- or
                      hyperthyroid diseases not requiring immunosuppressive treatment are eligible)
    
              -  Other severe acute or chronic medical conditions including immune-mediated colitis,
                 inflammatory bowel disease, pneumonitis, pulmonary fibrosis or psychiatric conditions
                 including recent (within the past year) or active suicidal ideation or behavior; or
                 laboratory abnormalities that may increase the risk associated with study
                 participation or study treatment administration or may interfere with the
                 interpretation of study results and, in the judgment of the investigator, would make
                 the patient inappropriate for entry into this study
    
              -  Known prior severe hypersensitivity to investigational product or any component in its
                 formulations, including known severe hypersensitivity reactions to monoclonal
                 antibodies (NCI CTCAE v4.03 grade >= 3) that could interfere with study endpoints or
                 put patient safety at risk
    
              -  Pregnant or breast-feeding women
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Relapse-free survival
    Time Frame:From the date of randomization and the date of first recurrence or death (whatever the cause), whichever occurs first, assessed for up to 5 years
    Safety Issue:
    Description:The Kaplan-Meier technique will be used to obtain estimates.

    Secondary Outcome Measures

    Measure:Disease-specific survival
    Time Frame:From the date of randomization and the date of death from Merkel cell carcinoma, assessed for up to 5 years
    Safety Issue:
    Description:Cumulative incidence estimates will be used to summarize the probabilities of disease-specific survival.
    Measure:Distant-metastases free survival
    Time Frame:From the date of randomization and the date of first distant metastasis or date of death (any cause), whichever occurs first, assessed for up to 5 years
    Safety Issue:
    Description:The Kaplan-Meier technique will be used to obtain estimates.
    Measure:Incidence of adverse events
    Time Frame:Throughout the duration of the treatment (up to 2 years after randomization)
    Safety Issue:
    Description:Graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.
    Measure:Overall survival
    Time Frame:From the date of randomization and the date of death, assessed for up to 5 years
    Safety Issue:
    Description:The Kaplan-Meier technique will be used to obtain estimates.

    Details

    Phase:Phase 3
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:University of Washington

    Last Updated