Adjuvant Nivolumab Treatment in Stage II (IIA, IIB, IIC) High-risk Melanoma

NCT04309409 | Active Not Recruiting Phase 3

• 1 other identifier: CA209-7DL
• Study Type: interventional
• Target: 374
• Locations: 1 country
• Sites: 20

Brief Summary

Stage II patients with primary surgical treatment of cuMM are often at risk for recurrence of their disease. This risk may be reduced by adjuvant systemic treatment. Due to toxicities of adjuvant therapies the aim is to identify patients at high risk for relapse and to administer adjuvant treatment only to these patients. Thus an optimal balance between insufficient treatment vs. overtreatment has to be found. To define these patients a prognostic biomarker test will be used in addition to conventional AJCC staging. AJCC staging takes into account several prognostic factors. However, to subdivide stage II melanoma patients into having a low or high risk for relapse further methods are needed. This clinical trial will evaluate whether adjuvant nivolumab treatment will improve relapse-free survival (RFS) in patients with stage II high-risk melanoma as compared to observation only. The randomized approach of this trial offers the most objective method with the least influence of bias. Since patients with stage II melanoma are usually not receiving adjuvant treatment, no patient will be undertreated in case of randomization into observational arm.

Conditions

Malignant Melanoma Stage II

Keywords

Stage II malignant melanoma; patients having undergone surgery; IIA melanoma; IIB melanoma; IIC melanoma

Outcome Measures

Primary Outcomes (1)

• Relapse-Free Survival (RFS) rates

  Determination of efficacy of nivolumab in a biomarker-selected high-risk-enriched stage II melanoma patient population in comparison to control receiving observation only in a 2 (Arm A=nivolumab) : 1 (Arm B=observation) randomization, as measured by Relapse-Free Survival (RFS) rates at 36 and 60 months. RFS is defined as the time from date of registration until documented tumor progression date or date of death of any cause, whichever occurs first in all patients tested with the MelaGenix gene expression profiling (GEP).

  5 years

Secondary Outcomes (5)

• Distant metastasis-free survival (DMFS) rates

  5 years

• Melanoma-specific survival (MSS) rates

  5 years

• Overall survival (OS) rates

  5 years

• Adverse events ≥ Grade 3 according to CTCAE Version 5.0 criteria (Safety / Toxicity)

  Arm A: Until 100 days after discontinuation of dosing of the investigational product; Arm B: Until 1 year after patient´s written consent

• Clinical utility/decision impact of the MelaGenix Gene Expression Profiling (GEP) Score in stratifying patients for adjuvant therapy

  5 years

Other Outcomes (2)

• Treatment-free interval (TFI)

  5 years

• Tumor mutational burden (TMB)

  5 years

Study Arms (3)

Nivolumab (Arm A)

EXPERIMENTAL

Patients with a risk score of \> 0.0 corresponding to high risk of relapse (randomized): Nivolumab will be applied at a flat dose of 480 mg given as 60-minute iv infusion every 4 weeks for 12 doses over 1 year. Afterwards these patients will receive intense clinical follow up according German Follow up guidelines.

Drug: Nivolumab

Observation, High Risk (Arm B)

NO INTERVENTION

Patients with a risk score of \> 0.0 corresponding to high risk of relapse (randomized): Control group (observation only). These patients will receive intense clinical follow up but no further specific therapy according German Follow up guidelines.

Observation, Low Risk (Arm C)

NO INTERVENTION

Patients with a risk score of ≤ 0.0 corresponding to low risk of relapse who are not eligible for randomization: These patients will receive intense clinical follow up but no further specific therapy according German Follow up guidelines. Documentation of clinical outcome of these patients.

Interventions

Nivolumab DRUG

480 mg nivolumab fixed dose given as 60-minute iv infusion every 4 weeks for 12 doses over 1 year

Also known as: Opdivo

Nivolumab (Arm A)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed diagnosis of stage II (AJCCv8) melanoma arising from a primary cutaneous site after surgery therapy
• Sentinel node biopsy (SNB) without detection of melanoma deposits
• Randomization not later than 12 weeks after SNB procedure
• Tumor tissue from primary tumor must be provided for biomarker analyses. In order to be randomized, a subject must be classified by MelaGenix risk analysis.
• Men and women at the age of 18 to 80 years
• Signed written, informed consent
• Patients must be willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other requirements of the study
• Minimum life expectancy of five years excluding their melanoma diagnosis
• ECOG performance status of 0-1
• Screening laboratory values must meet the following criteria and should be obtained within 14 days prior to randomization:
• White blood cells (WBC) ≥ 2000/μL
• Neutrophils ≥ 1500/μL
• Platelets ≥ 100 x103/μL
• Hemoglobin ≥ 9.0 g/dL
• Serum creatinine ≤ 1.5xUL

You may not qualify if:

• History of primary uveal or mucosal melanoma
• No access to sufficient tumor tissue of primary tumor
• SNB procedure \> 12 weeks before randomization
• Prior active malignancy within the previous 3 years except for locally curable cancers that have been apparently cured, such as: basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the prostate, cervix, or breast. Exception: Participants with a history of non-ulcerated cutaneous/acral primary melanoma \<1 mm in depth with no nodal involvement are allowed in this trial.
• Prior or planned therapy with Interferon alpha, CTLA4 or PD-1 / PD L1 antibodies
• Use of any investigational or non-registered product (drug or vaccine) other than the study treatment
• Administration of live vaccines within 4 weeks before start of study therapy
• Any immunosuppressive therapy given within the past 30 days
• Active psychiatric or addictive disorders that may compromise his/her ability to give informed consent or to comply with the trial procedures
• Active immune deficiencies or significant autoimmune disease
• Serious cardiac, gastrointestinal, hepatic or pulmonary disease which would reduce life expectancy to less than five years
• Serious intercurrent illness, requiring hospitalization
• Other serious illnesses, e.g., serious infections requiring antibiotics or bleeding disorders
• The patient is known to be positive for Human Immunodeficiency Virus (HIV) or other active chronic infections (HBV, HCV) or has another confirmed or suspected immunosuppressive or immunodeficient condition
• Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results.

Sponsors & Collaborators

• University Hospital, Essen: lead

Study Sites (20)

Universitätsklinikum Würzburg - Klinik für Dermatologie, Venerologie und Allergologie

Würzburg, Bavaria, 97080, Germany

Location

Universitätsmedizin Rostock -Klinik und Poliklinik für Dermatologie und Venerologie

Rostock, Mecklenburg-Vorpommern, 18057, Germany

Location

Universitätsklinikum Augsburg, Campus Süd

Augsburg, 86179, Germany

Location

St. Josef-Hospital - Dermatologische Studienambulanz

Bochum, 44791, Germany

Location

Klinikum Dortmund gGmbH - Dermatologie

Dortmund, 44137, Germany

Location

Universitätsklinik Carl Gustav Carus der Technischen Universität Dresden - Klinik und Poliklinik für Dermatologie

Dresden, 01307, Germany

Location

HELIOS Klinikum Erfurt

Erfurt, 99089, Germany

Location

University Hospital Essen, Department of Dermatology, Skin Cancer Center

Essen, 45122, Germany

Location

Universitätsklinikum Freiburg - Klinik für Dermatologie und Venerologie

Freiburg im Breisgau, 79106, Germany

Location

Universitätsklinikum Gießen und Marburg GmbH - Klinik für Dermatologie und Allergologie

Giessen, 35392, Germany

Location

Universitätsklinikum Hamburg-Eppendorf - Hauttumorzentrum

Hamburg, 20246, Germany

Location

Universitätsklinikum Schleswig-Holstein, Campus Kiel - Dermatologie

Kiel, 24105, Germany

Location

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

Leipzig, 04103, Germany

Location

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

Mannheim, 68167, Germany

Location

Klinikum der Universität München - Klinik und Poliklinik für Dermatologie und Allergologie

München, 80337, Germany

Location

Universitätsklinikum Münster - Zentrale Studienkoordination für innovative Dermatologie (ZID)

Münster, 48149, Germany

Location

Fachklinik Hornheide - Internistische Onkologie

Münster, 48157, Germany

Location

Klinikum Nürnberg Nord - Hautklinik

Nuremberg, 90419, Germany

Location

Harzklinikum Dorothea Christiane Erxleben - Klinik für Dermatologie & Allergologie

Quedlinburg, 06484, Germany

Location

Universitätsklinikum Tübingen - Dermatoonkologie

Tübingen, 72076, Germany

Location

MeSH Terms

Conditions

Melanoma

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

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 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of the Department of Dermatology and the West German Tumour Centre at the University Hospital

Model Details: Patients with a risk score of \> 0.0 (HR 1.48, 1.11-1.98) corresponding to high risk of relapse will be randomized at a ratio of 2:1 to receive either nivolumab as adjuvant treatment (arm A) or observation only (arm B). All screened patients with a risk score of ≤ 0.0 who are not eligible for randomization will be followed for RFS, DMFS and OS for at least 5 years according to German Follow-up guidelines (Arm C).

Study Record Dates

• First Submitted: March 12, 2020
• First Posted: March 16, 2020
• Study Start: July 1, 2020
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): January 1, 2028
• Last Updated: May 23, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

DE (20)