Study of Avelumab and/or Radiation Therapy in People With Advanced Merkel Cell Carcinoma

Merkel Cell Carcinoma Clinical Trial

Official title:

A Phase II Single-Arm Clinical Trial Assessing Comprehensive Ablative Radiation Therapy With Avelumab in Unresectable and Metastatic Merkel Cell Carcinoma (CARTA)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04792073
• Other study ID #: 20-195
• Status: Recruiting
• Phase: Phase 2
• Start date: March 8, 2021
• Est. completion date: March 2025

Study information

• Verified date: January 2024
• Source: Memorial Sloan Kettering Cancer Center
• Contact: Christoper Barker, MD
• Phone: 212-639-8168
• Email: barkerc[@]mskcc.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will test the use of comprehensive ablative radiation therapy (CART), with the immunotherapy drug avelumab, in people with Merkel cell carcinoma (MCC) that has progressed after treatment and cannot be removed with surgery. The study researchers want to find out if CART works well when combined with avelumab.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 18
• Est. completion date: March 2025
• Est. primary completion date: March 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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: 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
• 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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Merkel Cell
• Merkel Cell Carcinoma

Intervention

Drug:
• Avelumab
Avelumab 800 mg given intravenously over 60 minutes every 2 weeks (+/- 3 days)

Radiation:
• Comprehensive Ablative Radiation Therapy
Comprehensive ablative radiation therapy 24 Gy in 3 fractions every 2-3 days

Locations

Country	Name	City	State
United States	Memorial Sloan Kettering Basking Ridge (All Protocol Activities)	Basking Ridge	New Jersey
United States	Memorial Sloan Kettering Commack (All Protocol Activities)	Commack	New York
United States	Memorial Sloan Kettering Westchester (All Protocol Activities)	Harrison	New York
United States	Memorial Sloan Kettering Monmouth (All Protocol Activities)	Middletown	New Jersey
United States	Memorial Sloan Kettering Bergen (All Protocol Activities)	Montvale	New Jersey
United States	Memorial Sloan Kettering Cancer Center (All Protocol Activities)	New York	New York
United States	Memorial Sloan Kettering Nassau (All Protocol Activities)	Uniondale	New York

Sponsors (2)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center	EMD Serono

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	progression free survival	measured by RECIST 1.1	at 12 weeks
Secondary	overall response rate	measured by RECIST 1.1	up to 12 weeks

External Links

•   Memorial Sloan Kettering Cancer Center