Clinical Trials /

Pembrolizumab Compared to Standard of Care Observation in Treating Patients With Completely Resected Stage I-III Merkel Cell Cancer

NCT03712605

Description:

This phase III trial studies how well pembrolizumab works compared to standard of care observation in treating patients with stage I-III Merkel cell cancer that has been completely removed by surgery (resected). Immunotherapy with monoclonal antibodies, such as pembrolizumab, 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: Pembrolizumab Compared to Standard of Care Observation in Treating Patients With Completely Resected Stage I-III Merkel Cell Cancer
  • Official Title: A Phase III Randomized Trial Comparing Adjuvant MK-3475 (Pembrolizumab) to Standard of Care Observation in Completely Resected Merkel Cell Carcinoma

Clinical Trial IDs

  • ORG STUDY ID: NCI-2018-02217
  • SECONDARY ID: NCI-2018-02217
  • SECONDARY ID: EA6174
  • SECONDARY ID: EA6174
  • SECONDARY ID: U10CA180820
  • NCT ID: NCT03712605

Conditions

  • Pathologic Stage I Merkel Cell Carcinoma AJCC v8
  • Pathologic Stage II Merkel Cell Carcinoma AJCC v8
  • Pathologic Stage IIA Merkel Cell Carcinoma AJCC v8
  • Pathologic Stage IIB Merkel Cell Carcinoma AJCC v8
  • Pathologic Stage III Merkel Cell Carcinoma AJCC v8
  • Pathologic Stage IIIA Merkel Cell Carcinoma AJCC v8
  • Pathologic Stage IIIB Merkel Cell Carcinoma AJCC v8
  • Resected Mass

Interventions

DrugSynonymsArms
PembrolizumabKeytruda, Lambrolizumab, MK-3475, SCH 900475Arm A (pembrolizumab, radiation therapy)

Purpose

This phase III trial studies how well pembrolizumab works compared to standard of care observation in treating patients with stage I-III Merkel cell cancer that has been completely removed by surgery. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To compare overall survival (OS) and recurrence free survival (RFS) as co-primary
      endpoints across the two arms.

      SECONDARY OBJECTIVES:

      I. To evaluate adverse events. II. To evaluate distant metastasis free survival (DMFS). III.
      To evaluate the impact of radiation on clinical outcomes (OS, RFS, DMFS).

      OUTLINE: Patients are randomized to 1 of 2 arms.

      ARM A: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Treatment
      repeats every 21 days for up to 17 cycles in the absence of disease progression or
      unacceptable toxicity. Patients may also undergo standard of care radiation therapy within 14
      days of day 1, cycle 1.

      ARM B: Patients receive standard of care observation for 17 cycles. Patients may also undergo
      standard of care radiation therapy within 14 days of day 1, cycle 1.

      After completion of study treatment, patients are followed up every 6 months for 5 years.
    

Trial Arms

NameTypeDescriptionInterventions
Arm A (pembrolizumab, radiation therapy)ExperimentalPatients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 17 cycles in the absence of disease progression or unacceptable toxicity. Patients may also undergo standard of care radiation therapy within 14 days of day 1, cycle 1.
  • Pembrolizumab
Arm B (standard of care observation, radiation therapy)Active ComparatorPatients receive standard of care observation for 17 cycles. Patients may also undergo standard of care radiation therapy within 14 days of day 1, cycle 1.

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status: 0,
                 1, or 2 (However, those patients with a performance state of 3 because they are wheel
                 chair bound due to congenital or traumatic events more than one year before the
                 diagnosis of Merkel cell carcinoma are eligible).
    
              -  Women must not be pregnant or breast-feeding due to the unknown effects of the study
                 drug in this setting. All women of childbearing potential must have a blood test or
                 urine study within 2 weeks prior to registration to rule out pregnancy. A female of
                 childbearing potential is any woman, regardless of sexual orientation or whether they
                 have undergone tubal ligation, who meets the following criteria: 1) has achieved
                 menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy;
                 or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does
                 not rule out childbearing potential) for at least 24 consecutive months (i.e., has had
                 menses at any time in the preceding 24 consecutive months).
    
              -  Women of childbearing potential, and sexually active males, on Arm A MK-3475
                 (pembrolizumab must use accepted and effective method(s) of contraception or abstain
                 from sex from time of registration, while on study treatment, and continue for 120
                 days after the last dose of study treatment. For patients on Arm B only receiving
                 radiation therapy, contraception use should be per institutional standard.
    
              -  Patient must have a histological confirmation of diagnosis of Merkel cell carcinoma
                 (MCC), pathologic stages (American Joint Committee on Cancer [AJCC] version 8) I-IIIb.
    
                   -  Stage I patients with negative sentinel lymph node biopsy are ineligible.
                      Patients who have a positive biopsy or for whom no biopsy was done are eligible.
    
                   -  Patients with distant metastatic disease (stage IV) are not eligible.
    
                   -  The primary tumor must have negative margins.
    
              -  Patients with all macroscopic Merkel cell carcinoma (either identified by physical
                 exam or imaging) have been completely resected by surgery within 8 weeks before
                 registration.
    
              -  All patients must have disease-free status documented by a complete physical
                 examination and conventional imaging studies within 4 weeks prior to registration.
    
              -  Patient must have no currently present metastases (as confirmed by standard imaging
                 studies).
    
              -  Patient must have no previous systemic therapy or radiation therapy for Merkel cell
                 carcinoma.
    
              -  Patients with inoperable disease who have received radiation are not eligible.
    
              -  White blood count >= 2000/uL (within 4 weeks prior to randomization).
    
              -  Absolute neutrophil count (ANC) >= 1000/Ul (within 4 weeks prior to randomization).
    
              -  Platelets >= 75 x 10^3/uL (within 4 weeks prior to randomization).
    
              -  Hemoglobin >= 8 g/dL (>= 80 g/L; may be transfused) (within 4 weeks prior to
                 randomization).
    
              -  Creatinine =< 2.0 x upper limit of normal (ULN) (within 4 weeks prior to
                 randomization).
    
              -  Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x ULN (within 4
                 weeks prior to randomization).
    
              -  Total bilirubin =< 2.0 x ULN, (except patients with Gilbert's syndrome, who must have
                 a total bilirubin less than 3.0 mg/dL) (within 4 weeks prior to randomization).
    
              -  Patients who are human immunodeficiency virus (HIV)+ with undetectable HIV viral load
                 are eligible provided they meet all other protocol criteria for participation.
    
              -  Patients with hepatitis B virus (HBV) or hepatitis C virus (HCV) infection are
                 eligible provided viral loads are undetectable. Patients on suppressive therapy are
                 eligible.
    
              -  Patients must not be on active immunosuppression, have a history of life threatening
                 virus, have had other (beside non-melanoma skin cancers, or recent indolent cancers
                 e.g.: resected low grade prostate cancer) cancer diagnoses in the last two years, or
                 have had immunotherapy of any kind within the last 2 years.
    
              -  Patients must not have a history of (non-infectious) pneumonitis that required
                 steroids or has current pneumonitis.
    
              -  Operative notes from patient's surgical resection must be accessible.
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Recurrence free survival (RFS)
    Time Frame:From randomization until disease recurrence or death from any cause; assessed up to 4.5 years
    Safety Issue:
    Description:An intention-to-treat (ITT) analysis using the stratified log-rank test will be performed to compare overall survival (OS) and RFS between the two arms.

    Secondary Outcome Measures

    Measure:Impact of radiation therapy on RFS
    Time Frame:Up to 4.5 years
    Safety Issue:
    Description:RFS in each arm will be evaluated by radiation treatment status (radiation versus [vs.] no radiation therapy). The analysis will be a planned post-hoc analysis with primary goal of examining whether use of post-operative radiation therapy is associated with RFS. Cox multivariate models for RFS will be developed to evaluate the impact of radiation therapy while adjusting for pembrolizumab treatment and clinical/ pathological factors. The treatment fields and dose data will also be included in the Cox model as covariates. Secondary analyses for radiation therapy (RT) will examine factors associated with use of post-operative RT. Multivariate logistic regression models (radiation therapy vs. no radiation therapy) will be developed to evaluate the associations with demographic, clinical/pathologic, and treatment-related factors and pembrolizumab treatment.
    Measure:Impact of radiation therapy on OS
    Time Frame:Up to 4.5 years
    Safety Issue:
    Description:OS in each arm will be evaluated by radiation treatment status (radiation vs. no radiation therapy). The analysis will be a planned post-hoc analysis with primary goal of examining whether use of post-operative radiation therapy is associated with OS. Cox multivariate models for OS will be developed to evaluate the impact of radiation therapy while adjusting for pembrolizumab treatment and clinical/ pathological factors. The treatment fields and dose data will also be included in the Cox model as covariates. Secondary analyses for radiation therapy will examine factors associated with use of post-operative RT. Multivariate logistic regression models (radiation therapy vs. no radiation therapy) will be developed to evaluate the associations with demographic, clinical/pathologic, and treatment-related factors and pembrolizumab treatment.
    Measure:Impact of radiation therapy on distant metastasis free survival (DMFS)
    Time Frame:From randomization to distant metastasis, assessed up to 4.5 years
    Safety Issue:
    Description:DMFS will be evaluated by treatment arms. If there is no distant metastasis, cases will be censored at the time of last assessment.
    Measure:Incidence of adverse events per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
    Time Frame:Up to 4.5 years
    Safety Issue:
    Description:Adverse events from each arm will be summarized and compared using the Fisher's exact test.

    Details

    Phase:Phase 3
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:National Cancer Institute (NCI)

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