Adjuvant Therapy of Completely Resected Merkel Cell Carcinoma With Immune Checkpoint Blocking Antibodies vs Observation

NCT02196961 | Completed Phase 2

• 1 other identifier: CA184-205
• Study Type: interventional
• Target: 180
• Locations: 2 countries
• Sites: 20

Brief Summary

Primary objective: To estimate the efficacy of adjuvant nivolumab monotherapy in completely resected MCC patients Primary endpoint: Disease-free survival (DFS) rate evaluated at 12, 24 and 48 months after date of randomization Secondary Objectives: To describe the safety profile and additional efficacy parameters of the nivolumab treatment in MCC Secondary endpoints:

• Adverse events according to CTCAE, Version 4.0 criteria, that are related to the administration of nivolumab
• Disease-free survival (DFS)
• Overall survival (OS) and OS rates at 12, 24 and 48 months after randomization Explorative Endpoints:
• Distant-metastases-free survival (DMFS) and DMFS rate at 12, 24 and 48 months after randomization
• Identification and validation of prognostic/predictive biomarkers
• Quality of life (EORTC QLQ-C30) until 24 months after randomization

Conditions

Merkel Cell Carcinoma

Keywords

Merkel cell carcinoma; Adjuvant; Nivolumab

Outcome Measures

Primary Outcomes (3)

• Disease-free survival (DFS) rate at 12 months

  The number of patients alive and free of disease at 12 months after randomization in arm A compared to DFS in arm B.

  1 years post last patient first treatment/randomization

• Disease-free survival (DFS) rate at 24 months

  The number of patients alive and free of disease at 24 months after randomization

  2 years post last patient first treatment/randomization

• Disease-free survival (DFS) rate at 48 months

  The number of patients alive and free of disease at 48 months after randomization

  4 years post last patient first treatment/randomization

Secondary Outcomes (6)

• Number of adverse events

  1, 2 and 4 years post last patient first treatment/randomization

• Overall survival rate at 12 months

  1 year post last patient first treatment/randomization

• Overall survival rate at 24 months

  2 years post last patient first treatment/randomization

• Overall survival rate at 48 months

  4 years post last patient first treatment/randomization

• Disease-free survival (DFS)

  1, 2 and 4 years post last patient first treatment/randomization

Other Outcomes (5)

• Distant-metastases-free survival (DMFS) at 12 months after randomization

  1 year post last patient first treatment/randomization

• Distant-metastases-free survival (DMFS) at 24 months after randomization

  2 years post last patient first treatment/randomization

• Distant-metastases-free survival (DMFS) at 48 months after randomization

  4 years post last patient first treatment/randomization

Study Arms (2)

Observation

NO INTERVENTION

After complete resection of Merkel cell carcinoma, patients randomized to the observational arm will be observed only

Nivolumab

EXPERIMENTAL

After complete resection of Merkel cell carcinoma, patients randomized to the treatment arm will receive nivolumab at a fixed dose of 480 mg by IV infusion every 4 weeks for up to one year (i.e.13 doses).

Drug: Nivolumab

Interventions

Nivolumab DRUG

adjuvant treatment of completely resected Merkel cell carcinoma

Also known as: Opdivo

Nivolumab

Eligibility Criteria

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

You may qualify if:

• The patient is willing and able to give written informed consent.
• Central histological confirmation of diagnosis of Merkel cell carcinoma (MCC).
• All MCC manifestations have been completely resected by surgery within 12 weeks before enrolment.
• No currently present metastases (as confirmed by standard imaging studies (e.g. suggested by S2k guidelines)).
• No previous systemic therapy for MCC.
• Required values for initial laboratory tests:
• WBC ≥ 2000/uL
• ANC ≥ 1000/uL
• Platelets ≥ 75 x 103/uL
• Hemoglobin ≥ 8 g/dL (≥ 80 g/L)
• Creatinine ≤ 2.0 x ULN
• AST/ALT ≤ 2.5 x ULN
• Total Bilirubin ≤ 2.0 x ULN, (except patients with Gilbert's Syndrome, who must have a total bilirubin less than 3.0 mg/dL)
• ECOG performance status 0 or 1.
• No active or chronic infection with HIV, Hepatitis B (HBV) or C (HCV).

You may not qualify if:

• Autoimmune disease: Patients with a history of inflammatory bowel disease, including ulcerative colitis and Crohn's Disease, are excluded from this study, as are patients with a history of symptomatic disease requiring systemic steroids (e.g., rheumatoid arthritis, systemic progressive sclerosis, systemic lupus erythematosus, autoimmune vasculitis); autoimmune motor neuropathy.
• Other serious illnesses, e.g., serious infections requiring i.v. antibiotics.
• The patient is known to be positive for Human Immunodeficiency Virus (HIV) or other chronic infections (HBV, HCV) or has another confirmed or suspected immunosuppressive or immune deficient condition.
• Any underlying medical or psychiatric condition, which in the opinion of the investigator will make the administration of nivolumab hazardous or obscure the interpretation of adverse events (AEs), such as a condition associated with frequent diarrhea.
• Any non-oncology vaccine therapy for up to 1 month before or after any dose of nivolumab.
• A history of prior or current treatment with a T cell potentiating agent (e.g. IL-2, interferon, anti-CTLA-4, anti-CD137, anti-PD1, anti-PD-L1, or anti-OX40 antibody).
• Chronic use of immunosuppressive agents or systemic corticosteroids.
• Women of childbearing potential (WOCBP), defined above in Section 5.1, who:
• are unwilling or unable to use an acceptable method of contraception to avoid pregnancy for additional 5 months after the last dose of investigational product
• have a positive pregnancy test at baseline
• are pregnant or breastfeeding.
• The patient has psychiatric or addictive disorders that may compromise his/her ability to give informed consent or to comply with the trial procedures.
• Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness.
• Men of reproductive potential unwilling to use an adequate method to avoid pregnancy for additional 7 months after the last dose of investigational product.
• Use of any investigational or non-registered product (drug or vaccine) other than the study treatment.

Sponsors & Collaborators

• Prof. Dr. med. Dirk Schadendorf: lead
• Bristol-Myers Squibb: collaborator

Study Sites (20)

University Hospital Essen, Dermatology

Essen, North Rhine-Westphalia, 45122, Germany

Location

Charité Universitätsmedizin Berlin

Berlin, 10117, Germany

Location

Elbeklinikum Buxtehude

Buxtehude, 21614, Germany

Location

University Hospital Dresden, Dermatology

Dresden, 01307, Germany

Location

HELIOS Klinikum Erfurt

Erfurt, 99089, Germany

Location

Universitätsklinikum Freiburg

Freiburg im Breisgau, 79104, Germany

Location

SRH Wald-Klinikum Gera

Gera, 07548, Germany

Location

Hannover Medical School

Hanover, 30625, Germany

Location

National Centre for Tumour Diseases (NCT)

Heidelberg, 69120, Germany

Location

University Hospital Schleswig-Holstein, Kiel

Kiel, 24105, Germany

Location

Universitätsklinikum Leipzig Klinik u. Poliklinik f. Dermatologie, Venerologie u. Allergologie

Leipzig, 04103, Germany

Location

Universitätsklinikum Mainz Hautklinik und Poliklinik

Mainz, 55131, Germany

Location

Universitätsklinikum Mannheim Klinik f. Dermatologie, Venerologie u. Allergologie

Mannheim, 68167, Germany

Location

University Hospital München (LMU)

Munich, 80337, Germany

Location

Universitätsklinikum Münster Zentrale Studienkoordination für innovative Dermatologie (ZID)

Münster, 48149, Germany

Location

Specialist clinic in Hornheide

Münster, 48157, Germany

Location

Universitätsklinikum Regensburg

Regensburg, 93053, Germany

Location

University Hospital Tübingen

Tübingen, 72076, Germany

Location

Universitätsklinikum Würzburg Klinik u. Poliklinik f. Dermatologie, Venerologie u. Allergologie

Würzburg, 97080, Germany

Location

The Netherlands Cancer Institute / Antoni van Leeuwenhoek Hospital (NKI/AVL)

Amsterdam, 1066 CX, Netherlands

Location

Related Publications (1)

• Becker JC, Ugurel S, Leiter U, Meier F, Gutzmer R, Haferkamp S, Zimmer L, Livingstone E, Eigentler TK, Hauschild A, Kiecker F, Hassel JC, Mohr P, Fluck M, Thomas I, Garzarolli M, Grimmelmann I, Drexler K, Spillner AN, Eckhardt S, Schadendorf D; DeCOG. Adjuvant immunotherapy with nivolumab versus observation in completely resected Merkel cell carcinoma (ADMEC-O): disease-free survival results from a randomised, open-label, phase 2 trial. Lancet. 2023 Sep 2;402(10404):798-808. doi: 10.1016/S0140-6736(23)00769-9. Epub 2023 Jul 11.

  PMID: 37451295 DERIVED

MeSH Terms

Conditions

Carcinoma, Merkel Cell

Interventions

Nivolumab

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)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Dirk Schadendorf, Prof. Dr.

  University Hospital, Essen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof. Dr. med. Dirk Schadendorf

Study Record Dates

• First Submitted: June 20, 2014
• First Posted: July 22, 2014
• Study Start: June 1, 2014
• Primary Completion: August 31, 2024
• Study Completion: August 31, 2024
• Last Updated: April 9, 2025

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1); DE (19)