Clinical Trials /

Pembrolizumab With or Without Stereotactic Body Radiation Therapy in Treating Patients With Advanced or Metastatic Merkel Cell Cancer

NCT03304639

Description:

This randomized phase II trial studies how well pembrolizumab with or without stereotactic body radiation therapy works in treating patients with Merkel cell cancer that has spread to other places in the body. 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. Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method can kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. Giving pembrolizumab with stereotactic body radiation therapy may work better in treating patients with Merkel cell cancer.

Related Conditions:
  • Merkel Cell Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Pembrolizumab With or Without Stereotactic Body Radiation Therapy in Treating Patients With Advanced or Metastatic Merkel Cell Cancer
  • Official Title: A Randomized Phase II Study of Anti-PD1 Antibody [MK-3475 (Pembrolizumab)] Alone Versus Anti-PD1 Antibody Plus Stereotactic Body Radiation Therapy in Advanced Merkel Cell Carcinoma

Clinical Trial IDs

  • ORG STUDY ID: NCI-2017-01817
  • SECONDARY ID: NCI-2017-01817
  • SECONDARY ID: A091605
  • SECONDARY ID: A091605
  • SECONDARY ID: U10CA180821
  • NCT ID: NCT03304639

Conditions

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

Interventions

DrugSynonymsArms
PembrolizumabKeytruda, Lambrolizumab, MK-3475, SCH 900475Group I (pembrolizumab)

Purpose

This randomized phase II trial studies how well pembrolizumab with or without stereotactic body radiation therapy works in treating patients with Merkel cell cancer that has spread to other places in the body. 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. Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method can kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. Giving pembrolizumab with stereotactic body radiation therapy may work better in treating patients with Merkel cell cancer.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To describe the progression-free survival (PFS) of stereotactic body radiation therapy
      (SBRT) + pembrolizumab (MK-3475) compared to MK-3475 alone in advanced/metastatic Merkel cell
      carcinoma (MCC) patients.

      SECONDARY OBJECTIVES:

      I. To describe the PFS of SBRT + MK-3475 compared to MK-3475 alone across Response Evaluation
      Criteria in Solid Tumors (RECIST) measurable (including both radiated and non-radiated)
      cancer deposits.

      II. To describe the overall response rate of SBRT + MK-3475 compared to MK-3475 alone in both
      radiated and in non-radiated deposit(s).

      III. To determine the PFS at 6 months of SBRT + MK-3475 compared to MK-3475 alone across all
      cancerous deposits by RECIST.

      IV. To determine the rate of grade > 3-4 adverse events, by organ system, by Common
      Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0.

      V. To determine the local control of SBRT treated tumors. VI. To calculate delivered
      radiation dose using cone-beam computed tomography (CT) images collected on the radiation
      treatment table in the final treatment position.

      CORRELATIVE SCIENCE OBJECTIVES:

      I. To test the utility of CT-based radiomics to predict radiation-induced pneumonitis and
      true delivered dose of SBRT based on cone beam collected imaging and diagnostic scans.

      II. Biobanking for future correlative science projects.

      OUTLINE: Patients are randomized to 1 of 2 groups.

      GROUP I: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Cycles
      repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable
      toxicity.

      GROUP II: Patients receive pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21
      days for up to 2 years in the absence of disease progression or unacceptable toxicity.
      Patients also undergo SBRT for 3 doses during cycle 1.

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

Trial Arms

NameTypeDescriptionInterventions
Group I (pembrolizumab)Active ComparatorPatients receive pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
  • Pembrolizumab
Group II (pembrolizumab, SBRT)ExperimentalPatients receive pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo SBRT for 3 doses during cycle 1.
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must have pathologically (histologically or cytologically) proven diagnosis
             of MCC by local pathology review

          -  Have measurable disease based on RECIST 1.1 including at least two cancerous deposits;
             at least one deposit must be RECIST measurable while at least one deposit must meet
             criteria for SBRT; non-radiated tumor will be identified prior to randomization on the
             protocol

          -  Patients must have advanced or metastatic MCC defined as evidence of distant
             metastasis(es) on imaging

               -  Patients with locoregionally confined disease are not eligible

          -  No prior immunotherapy for advanced/metastatic MCC

          -  Patients with known or suspected central nervous system (CNS) metastases, untreated
             CNS metastases, or with the CNS as the only site of disease are excluded; however,
             subjects with controlled brain metastases will be allowed to enroll; controlled brain
             metastases are defined as no radiographic progression for at least 4 weeks following
             radiation and/or surgical treatment (or 4 weeks of observation if no intervention is
             clinically indicated), and off of steroids for at least 2 weeks, and no new or
             progressive neurological signs and symptoms

          -  Patients having received palliative radiotherapy for extracranial metastasis(es) are
             eligible as long as there are 2 cancerous deposits that have not received prior
             radiation therapy (RT) and they meet the following criteria

               -  No prior radiation therapy (> 5 Gy) to the metastasis intended to be treated with
                  SBRT

          -  No history of the following:

               -  Autoimmunity requiring systemic immunosuppression within 2 years

               -  Patients known to be human immunodeficiency virus (HIV) positive are eligible if
                  they meet the following:

                    -  CD4 counts >= 350 mm^3

                    -  Serum HIV viral load of < 25,000 IU/ml

          -  No other active malignancy that the investigator determines would interfere with the
             treatment and safety analysis

          -  Not pregnant and not nursing; therefore, for women of childbearing potential only, a
             negative (if your test schedule specifically indicates a urine or serum pregnancy
             test, add that information at this point) pregnancy test done =< 28 days prior to
             registration is required

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-2

          -  Absolute neutrophil count (ANC) >= 1,500/mm^3

          -  Platelet count >= 100,000/mm^3

          -  Hemoglobin >= 9.0 g/dl

          -  Total bilirubin =< 2.0 mg/dl

          -  Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3.0 x upper limit
             of normal (ULN)

          -  Systolic blood pressure (BP) =< 150 mg HG

          -  Diastolic BP =< 90 mg HG

          -  Albumin > 3 mg/dl

          -  Blood urea nitrogen (BUN) =< 30 mg/dl

          -  Creatinine =< 1.7 mg/dl

          -  The following imaging workup to document metastases within 45 days prior to study
             registration are required: CT scans of the chest, abdomen and pelvis with radionuclide
             bone scan OR whole body (at least skull base to midthigh) positron emission tomography
             (PET)/CT
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-free survival (PFS)
Time Frame:From randomization to either disease progression or death (without progression), assessed up to 5 years
Safety Issue:
Description:Will compare PFS in non-radiated lesion(s) of patients receiving either (a) stereotactic body radiation therapy (SBRT) + pembrolizumab compared to (b) pembrolizumab alone in patients with advanced Merkel cell carcinoma. Kaplan- Meier curves will be constructed and median PFS times will be calculated for each arm.

Secondary Outcome Measures

Measure:PFS among all Response Evaluation Criteria in Solid Tumors lesions
Time Frame:From randomization to either evidence of disease progression or death (without evidence of progression), assessed up to 5 years
Safety Issue:
Description:Same as the primary endpoint, but includes both irradiated and non-radiated lesions. It is a time to event endpoint and will be evaluated using the Kaplan- Meier method. Median PFS times will be calculated for each arm and a cox proportional hazards model will be constructed to determine if there is a PFS benefit for patients receiving SBRT + pembrolizumab compared to pembrolizumab alone.
Measure:Overall response rate
Time Frame:Up to 5 years
Safety Issue:
Description:Defined as partial response (PR) on 2 consecutive evaluations. Response rates will be calculated and compared across treatment arms utilizing a chi-square test.
Measure:Progression-free survival
Time Frame:At 6 months
Safety Issue:
Description:The rates of success will be calculated and compared across treatment arms utilizing a chi-square test.
Measure:Incidence of adverse events
Time Frame:Up to 3 months
Safety Issue:
Description:Graded according to National Cancer Institute's Common Terminology Criteria for Adverse Events, version 5.0. Maximum grade adverse events will be summarized by treatment arm in a tabular setting.
Measure:Local control of stereotactic body radiation therapy treated lesion
Time Frame:Up to 5 years
Safety Issue:
Description:The protocol irradiated tumors are considered to be controlled if they have no evidence of progression. No evidence of progression is defined as complete response (CR), PR, or stable disease (SD). Local control of the protocol-irradiated tumor will be described using the Kaplan-Meier technique.
Measure:Delivered radiation dose using cone-beam computed tomography (CT) images
Time Frame:Up to 5 years
Safety Issue:
Description:Radiation doses will be summarized descriptively and compared to the planned dose.

Details

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

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