Study of Avelumab and/or Radiation Therapy in People With 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 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.

Study Overview

• Status: Recruiting
• Conditions: Merkel Cell Carcinoma
• Intervention / Treatment: Drug: Avelumab; Radiation: Comprehensive Ablative Radiation Therapy

• Study Type: Interventional
• Enrollment (Estimated): 18
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Christoper Barker, MD; Phone Number: 212-639-8168; Email: barkerc@mskcc.org
• Study Contact Backup: Name: Sandra D'Angelo, MD; Phone Number: 646-888-4159

Study Locations

• United States
  • New Jersey
    • Basking Ridge, New Jersey, United States, 07920
      • Recruiting
      • Memorial Sloan Kettering Basking Ridge (All Protocol Activities)
      • Contact: Christopher Barker, MD; Phone Number: 212-639-8168
    • Middletown, New Jersey, United States, 07748
      • Recruiting
      • Memorial Sloan Kettering Monmouth (All Protocol Activities)
      • Contact: Christopher Barker, MD; Phone Number: 212-639-8168
    • Montvale, New Jersey, United States, 07645
      • Recruiting
      • Memorial Sloan Kettering Bergen (All Protocol Activities)
      • Contact: Christopher Barker, MD; Phone Number: 212-639-8168
  • New York
    • Commack, New York, United States, 11725
      • Recruiting
      • Memorial Sloan Kettering Commack (All protocol activities)
      • Contact: Christopher Barker, MD; Phone Number: 212-639-8168
    • Harrison, New York, United States, 10604
      • Recruiting
      • Memorial Sloan Kettering Westchester (All Protocol Activities)
      • Contact: Christopher Barker, MD; Phone Number: 212-639-8168
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering Cancer Center (All Protocol Activities)
      • Contact: MD
      • Contact: Christopher Barker, MD; Phone Number: 212-639-8168
    • Uniondale, New York, United States, 11553
      • Recruiting
      • Memorial Sloan Kettering Nassau (All Protocol Activities)
      • Contact: Christopher Barker, MD; Phone Number: 212-639-8168

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Avelumab and Radiation Therapy; Will receive avelumab at the FDA approved dose and schedule of 800 mg IV over 60 minutes every 2 weeks (+/- 3 days) until treatment intolerance or disease progression occurs or 2 years of study therapy have been administered; standard of care Avelumab therapy after 2 years is permitted. Comprehensive Ablative Radiation Therapy (CART) will be initiated between the first and second dose of Avelumab. Comprehensive ablative radiation therapy will be given according to guidelines.

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
progression free survival	measured by RECIST 1.1	at 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall response rate	measured by RECIST 1.1	up to 12 weeks

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborators: EMD Serono
• Investigators: Principal Investigator: Christoper Barker, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

Helpful Links

• Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): March 8, 2021
• Primary Completion (Estimated): March 1, 2025
• Study Completion (Estimated): March 1, 2025

Study Registration Dates

• First Submitted: March 8, 2021
• First Submitted That Met QC Criteria: March 8, 2021
• First Posted (Actual): March 10, 2021

Study Record Updates

• Last Update Posted (Estimated): January 8, 2024
• Last Update Submitted That Met QC Criteria: January 5, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: stage III; Avelumab; metastatic; unresectable; stage IV; Comprehensive Ablative Radiation Therapy; 20-195
• Additional Relevant MeSH Terms: Virus Diseases; Infections; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; DNA Virus Infections; Tumor Virus Infections; Neuroendocrine Tumors; Polyomavirus Infections; Carcinoma, Neuroendocrine; Carcinoma; Carcinoma, Merkel Cell; Antineoplastic Agents; Antineoplastic Agents, Immunological; Avelumab
• Other Study ID Numbers: 20-195

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No