Adjuvant Avelumab in Merkel Cell Cancer

NCT03271372 | Active Not Recruiting Phase 3 DMC FDA Drug

• 3 other identifiers: 9820NCI-2017-00998RG1717054
• Study Type: interventional
• Target: 101
• Locations: 1 country
• Sites: 9

Brief Summary

This randomized phase III trial studies how well avelumab works in treating patients with Merkel cell cancer that has spread to the lymph nodes and have undergone surgery and/or radiation therapy. Immunotherapy with monoclonal antibodies, such as avelumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Conditions

Stage IIIA Merkel Cell Carcinoma AJCC v8; Stage III Merkel Cell Carcinoma AJCC v8; Stage IIIB Merkel Cell Carcinoma AJCC v8

Outcome Measures

Primary Outcomes (1)

• Relapse-free survival

  The Kaplan-Meier technique will be used to obtain estimates.

  From the date of randomization and the date of first recurrence or death (whatever the cause), whichever occurs first, assessed for up to 5 years

Secondary Outcomes (4)

• Overall survival

  From the date of randomization and the date of death, assessed for up to 5 years then every 12 months after study drug discontinued

• Disease-specific survival

  From the date of randomization and the date of death from Merkel cell carcinoma, assessed for up to 5 years

• Distant-metastases free survival

  From the date of randomization and the date of first distant metastasis or date of death (any cause), whichever occurs first, assessed for up to 5 years

• Incidence of adverse events

  Throughout the duration of the treatment (up to 2 years after randomization)

Other Outcomes (2)

• AMERK serology

  Up to 5 years

• Biomarker exploration in tumor and peripheral blood samples

  Up to 5 years

Study Arms (2)

Arm I (avelumab)

EXPERIMENTAL

Patients receive avelumab IV over 1 hour once every 15 days for the first 120 days (Induction Phase 1), once every 30 days for the next 120 days (Induction Phase 2), and then once every 120 days (Maintenance Phase) for a maximum of 720 days (approximately 24 months or 2 years total) in the absence of disease progression or unacceptable toxicity.

Drug: Avelumab; Other: Peripheral Blood Collection

Arm II (placebo)

PLACEBO COMPARATOR

Patients receive placebo IV over 1 hour once every 15 days for the first 120 days (Induction Phase 1), once every 30 days for the next 120 days (Induction Phase 2), and then once every 120 days (Maintenance Phase) for a maximum of 720 days (approximately 24 months or 2 years total) in the absence of disease progression or unacceptable toxicity.

Other: Peripheral Blood Collection; Other: Placebo

Interventions

Avelumab DRUG

Given IV

Also known as: Bavencio, MSB-0010718C, MSB0010718C

Arm I (avelumab)

Peripheral Blood Collection OTHER

Correlative studies

Arm I (avelumab); Arm II (placebo)

Placebo OTHER

Given IV

Also known as: placebo therapy, PLCB, normal saline solution

Arm II (placebo)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed MCC metastases in regional lymph node(s)
• Confirmation of the MCC diagnosis in the regional lymph node(s) is mandatory for trial participation
• (NOTE: In-transit metastases without regional nodal involvement could be allowed, but only after written approval of the medical monitor)
• Must have completed definitive treatment for primary MCC and regional lymphatic metastases that included surgical removal (with/without adjuvant radiation therapy) or primary radiation therapy as determined by the treating investigator
• Aged \>= 18 years. Both men and women, and members of all races and ethnic groups are eligible for this trial.
• Estimated life expectancy greater than 3 years
• Must start the study treatment no more than 120 days from the start date of definitive therapy (the date of surgical removal of nodal metastases or the date of initiation of definitive radiation therapy, as applicable)
• Eastern Co-Operative Group (Eastern Cooperative Oncology Group \[ECOG\]) performance score of 0 or 1
• Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L
• Platelet count ≥ 100 x 10\^9/L
• Hemoglobin ≥ 9 g/dL (may have been transfused)
• Total bilirubin level ≤ 1.5 x the upper limit of normal (ULN) range
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels ≤ 2.5 x ULN
• Estimated creatinine clearance ≥ 30 mL/min according to the Cockcroft-Gault formula or by 24-hour urine collection for creatinine clearance or according to local institutional standard
• Women of childbearing potential must have a negative serum or urine pregnancy test at screening

You may not qualify if:

• Clinical or radiologic suspicion of residual MCC at the time of enrollment
• Suspicion or known history of distant metastatic MCC, which is not classifiable as local recurrence or regional metastasis
• Any prior systemic therapy (e.g. adjuvant, neo-adjuvant or concurrent use of chemotherapy, immunotherapy or an investigational agent) for MCC at any time
• Any prior intra-lesional MCC therapy within 180 days from day 1 of study treatment
• Residual toxicity from prior therapy grade \> 1 (National Cancer Institute \[NCI\]-Common Terminology Criteria for Adverse Events \[NCI-CTCAE v 5.0\]) that could interfere with study endpoints or put patient safety at risk
• Previous malignant disease (other than Merkel cell carcinoma) diagnosed within 3 years from day 1 of study treatment that could interfere with study endpoints or put patient safety at risk
• \* (NOTE: Exception will be made for adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ \[skin, bladder, cervical, colorectal, breast\] or low grade prostatic intraepithelial neoplasia or Grade 1 prostate cancer; any other neoplasm, which is adjudged by the treating investigator to have a low risk of recurrence during the study, could be enrolled only after written approval from the medical monitor)
• Use of any systemic immunosuppressive treatments including corticosteroids, cyclosporine, mycophenolate mofetil et cetera, ongoing or within the last 3 months prior to day 1 of treatment
• \* (NOTE: Patients on physiologic dose of corticosteroids \[≤ 10 mg/day of prednisone or equivalent\] for long-term hormone-replacement therapy or those requiring short, intermittent courses of corticosteroids for hypersensitivity prophylaxis \[such as for iodinated computed tomography (CT) contrast prophylaxis\] or those using intranasal, inhaled, topical steroids, or local steroid injection \[e.g., intra-articular injection\] can be allowed)
• Immunosuppressed status due to known human immunodeficiency virus (HIV) infection, severe uncontrolled diabetes, concurrent hematological malignancy, or other comorbidities
• Uncontrolled intercurrent illness including, but not limited to, active serious infection, active hepatitis B or hepatitis C infection, uncontrolled seizure disorder, substance abuse disorder, or psychiatric illness/social situations that would limit compliance with study requirements or would put the patient at increased risk of complications during the study period
• Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (\< 6 months prior to enrollment), myocardial infarction (\< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication
• Active or history of any serious autoimmune disease, prior organ transplantation, including allogeneic stem-cell transplantation or immune-deficiencies that required treatment with systemic immunosuppressive drugs and could flare-up during study treatment
• \* (NOTE: Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible)
• Other severe acute or chronic medical conditions including immune-mediated colitis, inflammatory bowel disease, pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study

Sponsors & Collaborators

• University of Washington: lead
• EMD Serono: collaborator

Study Sites (9)

University of California Irvine Chao Family Comprehensive Cancer Center

Orange, California, 92868, United States

Location

University of Colorado Cancer Center University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

University of North Carolina Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

Location

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Carcinoma, Merkel Cell

Interventions

avelumab; Saline Solution

Condition Hierarchy (Ancestors)

Polyomavirus Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Carcinoma, Neuroendocrine; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Shailender Bhatia

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 31, 2017
• First Posted: September 5, 2017
• Study Start: December 19, 2017
• Primary Completion: April 30, 2026
• Study Completion (Estimated): February 18, 2029
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (9)