Clinical trial NCT04792073: 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
Overall status: RECRUITING
Phase: PHASE2
Conditions: Merkel Cell Carcinoma
Keywords: unresectable
metastatic
stage III
stage IV
Comprehensive Ablative Radiation Therapy
Avelumab
20-195
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
Collaborators: name: EMD Serono
First posted: 2021-03-10
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: A Phase II Single-Arm Clinical Trial Assessing Comprehensive Ablative Radiation Therapy with Avelumab in Unresectable and Metastatic Merkel Cell Carcinoma (CARTA)
Primary purpose: TREATMENT

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.


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: 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

Primary outcomes:
measure: progression free survival
timeFrame: at 12 weeks
Secondary outcomes:
measure: overall response rate
timeFrame: up to 12 weeks
Other outcomes:
Locations:
city: Basking Ridge
country: United States
facility: Memorial Sloan Kettering Basking Ridge (All Protocol Activities)
state: New Jersey
city: Middletown
country: United States
facility: Memorial Sloan Kettering Monmouth (All Protocol Activities)
state: New Jersey
city: Montvale
country: United States
facility: Memorial Sloan Kettering Bergen (All Protocol Activities)
state: New Jersey
city: Commack
country: United States
facility: Memorial Sloan Kettering Commack (All Protocol Activities)
state: New York
city: Harrison
country: United States
facility: Memorial Sloan Kettering Westchester (All Protocol Activities)
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center (All Protocol Activities)
state: New York
city: Uniondale
country: United States
facility: Memorial Sloan Kettering Nassau (All Protocol Activities)
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Christoper Barker, MD
role: PRINCIPAL_INVESTIGATOR
References: