The classic website will no longer be available as of June 25, 2024. Please use the modernized ClinicalTrials.gov.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Testing the Addition of Radiation Therapy to Immunotherapy for Merkel Cell Carcinoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03304639
Recruitment Status : Active, not recruiting
First Posted : October 9, 2017
Results First Posted : February 8, 2024
Last Update Posted : March 25, 2024
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:
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 (advanced). 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.

Condition or disease Intervention/treatment Phase
Advanced Merkel Cell Carcinoma Clinical Stage III Cutaneous Merkel Cell Carcinoma AJCC v8 Clinical Stage IV Cutaneous Merkel Cell Carcinoma AJCC v8 Metastatic Merkel Cell Carcinoma Pathologic Stage III Cutaneous Merkel Cell Carcinoma AJCC v8 Pathologic Stage IIIA Cutaneous Merkel Cell Carcinoma AJCC v8 Pathologic Stage IIIB Cutaneous Merkel Cell Carcinoma AJCC v8 Pathologic Stage IV Cutaneous Merkel Cell Carcinoma AJCC v8 Biological: Pembrolizumab Radiation: Stereotactic Body Radiation Therapy Phase 2

Detailed Description:

PRIMARY OBJECTIVE:

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

SECONDARY OBJECTIVES:

I. To describe the PFS of SBRT + MK-3475 compared to pembrolizumab (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 + pembrolizumab (MK-3475) compared to pembrolizumab(MK-3475) alone in both radiated and in non-radiated deposit(s).

III. To determine the PFS at 6 months of SBRT + pembrolizumab (MK-3475) compared to pembrolizumab (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.

Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 9 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : June 12, 2018
Actual Primary Completion Date : June 7, 2022
Estimated Study Completion Date : September 22, 2024

Resource links provided by the National Library of Medicine


Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Active Comparator: Group I (pembrolizumab)
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.
 Biological: Pembrolizumab
Given IV
Other Names:
  • BCD-201
  • Keytruda
  • Lambrolizumab
  • MK-3475
  • Pembrolizumab Biosimilar BCD-201
  • SCH 900475
Experimental: Group II (pembrolizumab, SBRT)
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.
 Biological: Pembrolizumab
Given IV
Other Names:
  • BCD-201
  • Keytruda
  • Lambrolizumab
  • MK-3475
  • Pembrolizumab Biosimilar BCD-201
  • SCH 900475

Radiation: Stereotactic Body Radiation Therapy
Undergo SBRT
Other Names:
  • SABR
  • SBRT
  • Stereotactic Ablative Body Radiation Therapy


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Progression-free Survival (PFS) [ Time Frame: From randomization to either disease progression or death (without progression), assessed up to 3 years ]
    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. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions


Secondary Outcome Measures :
  1. 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 3 years ]
    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.

  2. Overall Response Rate [ Time Frame: Up to 3 years ]
    Defined as partial response (PR) on 2 consecutive evaluations. Response rates will be calculated and compared across treatment arms utilizing a chi-square test.

  3. Progression-free Survival [ Time Frame: At 6 months ]
    The rates of success will be calculated and compared across treatment arms utilizing a chi-square test.

  4. Incidence of Adverse Events [ Time Frame: Up to 3 months ]
    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.

  5. PFS for Lesions Chosen for Radiation Prior to Randomization [ Time Frame: Up to 3 years ]
    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, PR, or stable disease. Local control of the protocol-irradiated tumor will be described using the Kaplan-Meier technique.

  6. Delivered Radiation Dose Using Cone-beam Computed Tomography (CT) Images [ Time Frame: Up to 3 years ]
    Radiation doses will be summarized descriptively and compared to the planned dose.


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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, because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown; 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
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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): NCT03304639


Locations
Show Show 259 study locations
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Principal Investigator: Jason J Luke Alliance for Clinical Trials in Oncology
  Study Documents (Full-Text)

Documents provided by National Cancer Institute (NCI):
Study Protocol and Statistical Analysis Plan  [PDF] October 15, 2021

More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Layout table for additonal information
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT03304639    
Other Study ID Numbers: NCI-2017-01817
NCI-2017-01817 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
A091605 ( Other Identifier: Alliance for Clinical Trials in Oncology )
A091605 ( Other Identifier: CTEP )
U10CA180821 ( U.S. NIH Grant/Contract )
First Posted: October 9, 2017    Key Record Dates
Results First Posted: February 8, 2024
Last Update Posted: March 25, 2024
Last Verified: March 2024

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Carcinoma, Merkel Cell
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Polyomavirus Infections
DNA Virus Infections
Virus Diseases
Infections
Tumor Virus Infections
Carcinoma, Neuroendocrine
 Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Adenocarcinoma
Neoplasms, Nerve Tissue
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action