Study of Avelumab and / or Radiation Therapy for Treatment of Stage III-IV Merkel Cell Carcinoma
- Biopsy proven Merkel cell carcinoma which is unresectable or metastatic, stage III or IV
- Prior first-line treatment with aPD1 monotherapy (defined as at least one dose of pembrolizumab, avelumab, nivolumab, etc.) with evidence of progression of disease >= 10 weeks after starting therapy, in the absence of significant clinical deterioration * Patients with progression in only one of several responding metastases will not be eligible * Patients with clinical deterioration during aPD1 monotherapy are eligible >= 6 weeks after starting aPD1 therapy ** Criteria for clinical deterioration to be determined and agreed upon by treating physician and Principal Investigator
- All detectable sites of MCC are amenable to comprehensive ablative radiation therapy in opinion of treating radiation oncologist and principal investigator
- >= 18 years of age
- Performance status =< 2 on the Eastern Cooperative Oncology Group performance scale
- Able to provide valid written informed consent
- Lymphocyte count >= 800/mm^3
- Neutrophil count >= 1500/mm^3
- Platelet count >= 75,000/mm^3
- Leukocyte count >= 3000/mm^3
- Hemoglobin >= 9 g/dL
- Total bilirubin =< 1.5 times the upper limit of normal, unless Gilbert’s syndrome
- Aspartate transaminase and alanine transaminase =< 2.5 times the upper limit of normal (in the absence of hepatobiliary metastases)
- =< 3.0 times the upper limit of normal (in the presence of hepatobiliary metastases)
- Estimated creatinine clearance >= 30 mL/min according to the Cockcroft-Gault formula
- Prior systemic therapy for MCC other than first-line aPD1 monotherapy (ie, chemotherapy)
- Pregnancy or breastfeeding
- Adverse events due to prior cancer therapy which are grade 3 or higher and have not resolved * Patients with prior grade 3 or higher immune related adverse events are not eligible, even if they have resolved
- Prior severe hypersensitivity reaction (Common Terminology Criteria for Adverse Events [CTCAE] version 5.0 grade >= 3) to avelumab
- Prior radiotherapy which precludes the ability to safely deliver comprehensive ablative radiation therapy in the opinion of the treating radiation oncologist and principal investigator * Institutional guidelines for reirradiation will be used when making this determination
- Known central nervous system metastases
- Known clinically significant cardiovascular disease, defined as: * Stroke or myocardial infarction within 6 months of first dose of avelumab * Symptomatic congestive heart failure (New York Heart Association class 2 or higher) * Serious arrhythmia requiring anti-arrhythmic agents
- Known human immunodeficiency virus infection
- Known hepatitis B or C infection requiring ongoing treatment
- Vaccination within 4 weeks of first dose of avelumab * Inactivated vaccines are permissible
- Iatrogenic immunosuppression with daily systemic corticosteroid equivalent of > 10 mg of prednisone
- Active autoimmune disease that may cause clinical deterioration during immunotherapy * Including, but not limited to: ** Inflammatory bowel disease or immune colitis ** Immune mediated pneumonitis or pulmonary fibrosis
- History of solid organ or hematopoietic transplant
- Active infection requiring systemic therapy
- Active suicidal ideation or behavior
- Comorbid or diagnostic abnormalities which would interfere with interpretation of study results
- Known hematopoietic cancer or dysfunction (i.e., leukemia, lymphoma)
- Known non-MCC solid tumor with known metastasis or estimated risk of metastasis > 20% within 3 months
I. To determine the efficacy of CART with or without avelumab in patients with unresectable or metastatic Merkel cell carcinoma (MCC) refractory to or recurrent after first-line aPD1 monotherapy.
I. To assess the overall response rate after CART with or without avelumab in patients with unresectable or metastatic MCC refractory to or recurrent after first-line aPD1 monotherapy.
II. To assess the adverse events that occur within 12 weeks of treatment with CART with or without avelumab in patients with unresectable or metastatic MCC refractory or recurrent after first-line aPD1 monotherapy.
II. To assess duration of overall survival, disease progression-free survival and freedom from additional treatment after completion of protocol treatment.
I. To explore the changes in immune system parameters and circulating viral DNA measured in peripheral blood collected during the course of treatment.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM A: Patients receive avelumab intravenously (IV) over 60 minutes every 2 weeks. Cycles repeat every 2 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo comprehensive ablative radiation therapy for 3 sessions over 5-14 days between the first and second dose of avelumab in the absence of disease progression or unacceptable toxicity.
ARM B: Patients undergo comprehensive ablative radiation therapy for 3 sessions over 5-14 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 12 weeks.
Trial Phase Phase II
Trial Type Treatment
Memorial Sloan Kettering Cancer Center
Christopher Andrew Barker
- Primary ID 20-195
- Secondary IDs NCI-2021-02157
- Clinicaltrials.gov ID NCT04792073