search
Back to results

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

Primary Purpose

Merkel Cell Carcinoma

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Avelumab
Comprehensive Ablative Radiation Therapy
Sponsored by
Memorial Sloan Kettering Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Merkel Cell Carcinoma focused on measuring unresectable, metastatic, stage III, stage IV, Comprehensive Ablative Radiation Therapy, Avelumab, 20-195

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 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
  • 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

Sites / Locations

  • Memorial Sloan Kettering Basking Ridge (All Protocol Activities)Recruiting
  • Memorial Sloan Kettering Monmouth (All Protocol Activities)Recruiting
  • Memorial Sloan Kettering Bergen (All Protocol Activities)Recruiting
  • Memorial Sloan Kettering Commack (All Protocol Activities)Recruiting
  • Memorial Sloan Kettering Westchester (All Protocol Activities)Recruiting
  • Memorial Sloan Kettering Cancer Center (All Protocol Activities)Recruiting
  • Memorial Sloan Kettering Nassau (All Protocol Activities)Recruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Avelumab and Radiation Therapy

Arm Description

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.

Outcomes

Primary Outcome Measures

progression free survival
measured by RECIST 1.1

Secondary Outcome Measures

overall response rate
measured by RECIST 1.1

Full Information

First Posted
March 8, 2021
Last Updated
September 20, 2023
Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
EMD Serono
search

1. Study Identification

Unique Protocol Identification Number
NCT04792073
Brief Title
Study of Avelumab and/or Radiation Therapy in People With Advanced Merkel Cell Carcinoma
Official Title
A Phase II Single-Arm Clinical Trial Assessing Comprehensive Ablative Radiation Therapy With Avelumab in Unresectable and Metastatic Merkel Cell Carcinoma (CARTA)
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 8, 2021 (Actual)
Primary Completion Date
March 2025 (Anticipated)
Study Completion Date
March 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
EMD Serono

4. Oversight

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

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Merkel Cell Carcinoma
Keywords
unresectable, metastatic, stage III, stage IV, Comprehensive Ablative Radiation Therapy, Avelumab, 20-195

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
A Phase II Single-Arm Clinical Trial Assessing Comprehensive Ablative Radiation Therapy with Avelumab in Unresectable and Metastatic Merkel Cell Carcinoma (CARTA)
Masking
None (Open Label)
Allocation
N/A
Enrollment
18 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Avelumab and Radiation Therapy
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Avelumab
Intervention Description
Avelumab 800 mg given intravenously over 60 minutes every 2 weeks (+/- 3 days)
Intervention Type
Radiation
Intervention Name(s)
Comprehensive Ablative Radiation Therapy
Intervention Description
Comprehensive ablative radiation therapy 24 Gy in 3 fractions every 2-3 days
Primary Outcome Measure Information:
Title
progression free survival
Description
measured by RECIST 1.1
Time Frame
at 12 weeks
Secondary Outcome Measure Information:
Title
overall response rate
Description
measured by RECIST 1.1
Time Frame
up to 12 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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: 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Christoper Barker, MD
Phone
212-639-8168
Email
barkerc@mskcc.org
First Name & Middle Initial & Last Name or Official Title & Degree
Sandra D'Angelo, MD
Phone
646-888-4159
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christoper Barker, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Memorial Sloan Kettering Basking Ridge (All Protocol Activities)
City
Basking Ridge
State/Province
New Jersey
ZIP/Postal Code
07920
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christopher Barker, MD
Phone
212-639-8168
Facility Name
Memorial Sloan Kettering Monmouth (All Protocol Activities)
City
Middletown
State/Province
New Jersey
ZIP/Postal Code
07748
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christopher Barker, MD
Phone
212-639-8168
Facility Name
Memorial Sloan Kettering Bergen (All Protocol Activities)
City
Montvale
State/Province
New Jersey
ZIP/Postal Code
07645
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christopher Barker, MD
Phone
212-639-8168
Facility Name
Memorial Sloan Kettering Commack (All Protocol Activities)
City
Commack
State/Province
New York
ZIP/Postal Code
11725
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christopher Barker, MD
Phone
212-639-8168
Facility Name
Memorial Sloan Kettering Westchester (All Protocol Activities)
City
Harrison
State/Province
New York
ZIP/Postal Code
10604
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christopher Barker, MD
Phone
212-639-8168
Facility Name
Memorial Sloan Kettering Cancer Center (All Protocol Activities)
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christopher Barker, MD
Phone
212-639-8168
First Name & Middle Initial & Last Name & Degree
MD
Facility Name
Memorial Sloan Kettering Nassau (All Protocol Activities)
City
Uniondale
State/Province
New York
ZIP/Postal Code
11553
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christopher Barker, MD
Phone
212-639-8168

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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.
Links:
URL
http://www.mskcc.org/mskcc/html/44.cfm
Description
Memorial Sloan Kettering Cancer Center

Learn more about this trial

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

We'll reach out to this number within 24 hrs