Combining Avelumab with Radiation Therapy for Advanced Merkel Cell Carcinoma
A Phase II Single-Arm Clinical Trial Assessing Comprehensive Ablative Radiation Therapy With Avelumab in Unresectable and Metastatic Merkel Cell Carcinoma (CARTA)
This study is testing if combining a radiation treatment with the drug avelumab can help people with advanced Merkel cell carcinoma whose cancer has not improved with previous therapies.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 18 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Memorial Sloan Kettering Cancer Center Academic / other |
| Drugs / interventions | pembrolizumab, avelumab, nivolumab, chemotherapy, immunotherapy, radiation, prednisone, CART |
| Locations | 7 sites (Basking Ridge, New Jersey and 6 other locations) |
| Trial ID | NCT04792073 on ClinicalTrials.gov |
What this trial studies
This study investigates the effectiveness of combining comprehensive ablative radiation therapy (CART) with the immunotherapy drug avelumab in patients with advanced Merkel cell carcinoma (MCC) that is unresectable or metastatic. Participants must have previously received first-line treatment with PD-1 inhibitors and show disease progression. The goal is to determine if this combination can improve treatment outcomes for patients whose cancer has not responded to prior therapies.
Who should consider this trial
Good fit: Ideal candidates are adults aged 18 and older with biopsy-proven unresectable or metastatic Merkel cell carcinoma who have progressed after first-line PD-1 inhibitor therapy.
Not a fit: Patients with early-stage Merkel cell carcinoma or those who have not received prior PD-1 inhibitor therapy may not benefit from this study.
Why it matters
Potential benefit: If successful, this approach could provide a new treatment option for patients with advanced Merkel cell carcinoma who have limited options.
How similar studies have performed: Other studies have shown promising results with similar combinations of immunotherapy and radiation therapy, suggesting potential for success in this approach.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * 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 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 * Normal organ and marrow function * Hematologic: Neutrophil count ≥1500/mm\^3, platelet count ≥100,000/mm\^3, hemoglobin ≥9 g/dL * Hepatic: 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) * Renal: Estimated creatinine clearance ≥ 30 mL/min according to the Cockcroft-Gault formula. Exclusion Criteria: * 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 (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
Where this trial is running
Basking Ridge, New Jersey and 6 other locations
- Memorial Sloan Kettering Basking Ridge (All Protocol Activities) — Basking Ridge, New Jersey, United States (Recruiting)
- Memorial Sloan Kettering Monmouth (All Protocol Activities) — Middletown, New Jersey, United States (Recruiting)
- Memorial Sloan Kettering Bergen (All Protocol Activities) — Montvale, New Jersey, United States (Recruiting)
- Memorial Sloan Kettering Commack (All Protocol Activities) — Commack, New York, United States (Recruiting)
- Memorial Sloan Kettering Westchester (All Protocol Activities) — Harrison, New York, United States (Recruiting)
- Memorial Sloan Kettering Cancer Center (All Protocol Activities) — New York, New York, United States (Recruiting)
- Memorial Sloan Kettering Nassau (All Protocol Activities) — Uniondale, New York, United States (Recruiting)
Study contacts
- Principal investigator: Christoper Barker, MD — Memorial Sloan Kettering Cancer Center
- Study coordinator: Christoper Barker, MD
- Email: barkerc@mskcc.org
- Phone: 212-639-8168
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.