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Merkel Cell CarcinomaPhase 2ADMEC-ONCT02196961

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

A Phase 2 study testing Nivolumab in people with Merkel Cell Carcinoma, run by Prof. Dr. med. Dirk Schadendorf at 20 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Merkel Cell Carcinoma
What is being tested?
Nivolumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
180 participants
Where
20 sitesin 2 countries
Study dates
Jun 2014to 31 Aug 2024
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
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  • 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).
  • Men and women, ≥ 18 years of age.
  • Women of childbearing potential (WOCBP) must be using an adequate method of contraception (Pearl-Index < 1) to avoid pregnancy during treatment phase and for additional 5 months after the last dose of nivolumab, in such a manner that the risk of pregnancy is minimized. WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not post-menopausal. WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours before the start of nivolumab.
  • Men of fathering potential must be using an adequate method of contraception to avoid conception and for 7 months after the last dose of nivolumab in such a manner that the risk of pregnancy is minimized.

Who cannot join

  • 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).
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  • 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.

Trial locations and contacts

20 sites in 2 countries.

20 sites in 2 countries

Germany19 sites

  • Charité Universitätsmedizin Berlin

    Berlin, 10117

  • Elbeklinikum Buxtehude

    Buxtehude, 21614

  • University Hospital Dresden, Dermatology

    Dresden, 01307

  • HELIOS Klinikum Erfurt

    Erfurt, 99089

  • University Hospital Essen, Dermatology

    Essen, North Rhine-Westphalia, 45122

  • Universitätsklinikum Freiburg

    Freiburg im Breisgau, 79104

  • SRH Wald-Klinikum Gera

    Gera, 07548

  • Hannover Medical School

    Hanover, 30625

  • National Centre for Tumour Diseases (NCT)

    Heidelberg, 69120

  • University Hospital Schleswig-Holstein, Kiel

    Kiel, 24105

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

    Leipzig, 04103

  • Universitätsklinikum Mainz Hautklinik und Poliklinik

    Mainz, 55131

  • Universitätsklinikum Mannheim Klinik f. Dermatologie, Venerologie u. Allergologie

    Mannheim, 68167

  • University Hospital München (LMU)

    Munich, 80337

  • Universitätsklinikum Münster Zentrale Studienkoordination für innovative Dermatologie (ZID)

    Münster, 48149

  • Specialist clinic in Hornheide

    Münster, 48157

  • Universitätsklinikum Regensburg

    Regensburg, 93053

  • University Hospital Tübingen

    Tübingen, 72076

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

    Würzburg, 97080

Other trials in Germany

Netherlands1 site

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

    Amsterdam, 1066 CX

Other trials in Netherlands

About this study

Official title: Prospective Randomized Trial of an Adjuvant Therapy of Completely Resected Merkel Cell Carcinoma (MCC) With Immune Checkpoint Blocking Antibodies (Nivolumab, Opdivo®; Ipilimumab (Yervoy®) Every 3 Weeks for 12 Weeks Versus Observation

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

Read more

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
Read the detailed description

This is an international, open-label, randomized, multicenter phase II study to assess the efficacy of adjuvant nivolumab therapy in completely resected MCC patients. In the initial trial design, the immune modulating treatment was based on CTLA-4 blockade by ipilimumab; however, the advent of PD-1/PD-L1 blockade in the palliative treatment of MCC (presented at AACR, ASCO and ESMO) dramatically changed the treatment environment to an extent that applying treatments other than by PD-1/PD-L1 blockade had become very difficult. Moreover, the side effects of PD-1/PD-L1 blocking are far less frequent than side effects of ipilimumab. Consequently, randomization into the previous Ipilimumab treatment arm A was stopped. New patients will be randomized to nivolumab treatment instead. Patients randomized already into the Ipilimumab-arm will be evaluated descriptively for efficacy and safety. Patients already randomized into the observation arm (arm B) will be evaluated together with the newly randomized arm B-patients. A total of 177 patients with completely resected MCC will be enrolled over a recruitment period of 36 months into this trial, and randomized 2:1 as mentioned above. Patients will be stratified by sex, age, and stage of disease.

Examinations and Follow-up Phase:

The disease will be assessed at baseline, and thereafter every 12 weeks according to the current German guidelines for the management of MCC patients for 24 months after randomization, or until withdrawal of informed consent, lost to follow-up, or death, whichever occurs first. In addition, the patient's quality of life will be evaluated at baseline (pretreatment visit) and every 3 months until 24 months after randomization using a standard questionnaire (EORTC QLQC30).

After 24 months, additional FU visits (or phone calls) will be conducted 6-monthly recording survival and tumor status including subsequent therapies until withdrawal of informed consent, lost to follow-up, death or end of study, whichever occurs first.

End of study is defined as 48 months post LPFV (last patient first visit = date of randomization).

Same methods of assessment (e.g. ultrasonography, CT or MRI scans) used at baseline will be used during follow-up.

Being tested
Nivolumab
Keywords
Merkel cell carcinoma, Adjuvant, Nivolumab
Medical subject headings
Carcinoma, Merkel Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NivolumabDrug

    Also called Opdivo

    adjuvant treatment of completely resected Merkel cell carcinoma

Study groups in NCT02196961
Study groupRoleWhat they receive
ObservationNo interventionAfter complete resection of Merkel cell carcinoma, patients randomized to the observational arm will be observed only
NivolumabExperimentalAfter 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).
Receives: Drug: Nivolumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 1 years post last patient first treatment/randomization

  2. Disease-free survival (DFS) rate at 24 months

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

    Measured: 2 years post last patient first treatment/randomization

  3. Disease-free survival (DFS) rate at 48 months

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

    Measured: 4 years post last patient first treatment/randomization

Secondary outcomes (6)

  1. Number of adverse events

    Adverse events according to CTCAE, Version 4.0 criteria, that are related to the administration of Ipilimumab

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

  2. Overall survival rate at 12 months

    Overall survival rate at 12 months, defined as the number of patients alive at 12 months after randomization divided by the total number of patients randomized.

    Measured: 1 year post last patient first treatment/randomization

  3. Overall survival rate at 24 months

    Overall survival rate at 24 months, defined as the number of patients alive at 24 months after randomization divided by the total number of patients randomized.

    Measured: 2 years post last patient first treatment/randomization

  4. Overall survival rate at 48 months

    Overall survival rate at 48 months, defined as the number of patients alive at 48 months after randomization divided by the total number of patients randomized.

    Measured: 4 years post last patient first treatment/randomization

  5. Disease-free survival (DFS)

    Time from randomization to recurrence of tumor

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

  6. Overall survival (OS)

    Time from randomization to death of patient

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Jul 2014 (estimated)
  2. Study startJun 2014
  3. Primary completion31 Aug 2024
  4. Study completion31 Aug 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
180 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02196961
Sponsor's protocol ID
CA184-205
Acronym
ADMEC-O
Status last verified
Nov 2024
First submitted
20 Jun 2014
Last updated
9 Apr 2025
Results posted
No
Data monitoring committee
No
Individual data sharing
No

Publications

  • 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.

    PubMed 37451295

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Nivolumab in people with Merkel Cell Carcinoma, run by Prof. Dr. med. Dirk Schadendorf at 20 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 20 sites in Germany, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Disease-free survival (DFS) rate at 12 months (time frame: 1 years post last patient first treatment/randomization). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02196961, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Apr 2025.

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