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
Overview
- Phase
- Phase 2
- Intervention
- Pembrolizumab
- Conditions
- Advanced Merkel Cell Carcinoma
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 9
- Locations
- 510
- Primary Endpoint
- Progression-free Survival (PFS)
- Status
- Active, Not Recruiting
- Last Updated
- 19 days ago
Overview
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.
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.
Investigators
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
Exclusion Criteria
- Not provided
Arms & Interventions
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.
Intervention: Pembrolizumab
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.
Intervention: Stereotactic Body Radiation Therapy
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.
Intervention: Pembrolizumab
Outcomes
Primary Outcomes
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 Outcomes
- Progression-free Survival(At 6 months)
- Incidence of Adverse Events(Up to 3 months)
- PFS Among All Response Evaluation Criteria in Solid Tumors Lesions(From randomization to either evidence of disease progression or death (without evidence of progression), assessed up to 3 years)
- PFS for Lesions Chosen for Radiation Prior to Randomization(Up to 3 years)
- Overall Response Rate(Up to 3 years)
- Delivered Radiation Dose Using Cone-beam Computed Tomography (CT) Images(Up to 3 years)