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

Study Purpose

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.#46; 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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years - 80 Years
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

1. Histologically confirmed diagnosis of stage II (AJCCv8) melanoma arising from a primary cutaneous site after surgery therapy 2. Sentinel node biopsy (SNB) without detection of melanoma deposits 3. Randomization not later than 12 weeks after SNB procedure 4. 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. 5. Men and women at the age of 18 to 80 years 6. Signed written, informed consent 7. Patients must be willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other requirements of the study 8. Minimum life expectancy of five years excluding their melanoma diagnosis 9. ECOG performance status of 0-1 10. 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 - Creatinine clearance (CrCl) ≥ 40mL/min (using the Cockcroft-Gault formula) - AST / ALT ≤ 3 x ULN - Total Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert Syndrome, who may have total bilirubin < 3.0 mg/dL) 11.
Negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) for women of childbearing potential (WOCBP) within 72 hours prior to registration. Women will be considered to be of childbearing potential unless surgically sterilized (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy), or being post-menopausal for at least 24 months or being amenorrheic for > 12 months and follicle-stimulating hormone (FSH) levels ≥ 40 IU/L. 12. WOCBP and male patients with partners of childbearing potential must agree to always use a highly effective form of contraception according to CTFG during the course of this study and for at least 5 months after last dose of study medication (in Arm A only).

Exclusion Criteria:

1. History of primary uveal or mucosal melanoma 2. No access to sufficient tumor tissue of primary tumor 3. SNB procedure > 12 weeks before randomization 4. 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. 5. Prior or planned therapy with Interferon alpha, CTLA4 or PD-1 / PD L1 antibodies 6. Use of any investigational or non-registered product (drug or vaccine) other than the study treatment 7. Administration of live vaccines within 4 weeks before start of study therapy 8. Any immunosuppressive therapy given within the past 30 days 9. Active psychiatric or addictive disorders that may compromise his/her ability to give informed consent or to comply with the trial procedures 10. Active immune deficiencies or significant autoimmune disease 11. Serious cardiac, gastrointestinal, hepatic or pulmonary disease which would reduce life expectancy to less than five years 12. Serious intercurrent illness, requiring hospitalization 13. Other serious illnesses, e.g., serious infections requiring antibiotics or bleeding disorders 14. 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 15. 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. 16. Hypersensitivity to the active substance or to any of the excipients 17. Participation in another clinical study within the 30 days before registration 18. For female patients: Pregnancy or breast-feeding 19. For WOCBP and male patients with partners of childbearing potential: Refusal or inability to use effective means of contraception 20. Lack of availability for clinical follow-up assessments 21. Legal incapacity or limited legal capacity

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT04309409
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 3
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

University Hospital, Essen
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Dirk Schadendorf, Prof. Dr.
Principal Investigator Affiliation University Hospital, Essen
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other
Overall Status Recruiting
Countries Germany
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Malignant Melanoma Stage II
Additional Details

The NivoMela trial is a randomized, controlled, prospective, multi-center national phase III trial with biomarker-based risk stratification. Stage II melanoma patients having undergone surgery of the malignant melanoma will be screened using the MelaGenix GEP score to identify patients at high risk for relapse. It is expected, that 61% of screened patients will belong to this group. 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). Stratification factors for randomization are: 1. Tumor stage: IIA versus IIB versus IIC 2. Gender: Female versus Male 3. Site of primary tumor: extremities versus trunk versus head &neck 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). Various factors that could potentially predict clinical response and incidence of AEs to treatment with nivolumab will be investigated in peripheral blood and tumor specimen taken at baseline. Data from these investigations will be evaluated for associations with clinical efficacy (eg, ORR, PFS, OS) and safety/toxicity (AE). The samples may also be used for exploratory analyses to assess biomarkers associated with melanoma and/or with immunotherapy treatment.

Arms & Interventions

Arms

Experimental: Nivolumab (Arm A)

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.

No Intervention: Observation, High Risk (Arm B)

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.

No Intervention: Observation, Low Risk (Arm C)

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

Drug: - Nivolumab

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

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

International Sites

Augsburg, Germany

Status

Recruiting

Address

Universitätsklinikum Augsburg, Campus Süd

Augsburg, , 86179

Site Contact

Julia Welzel, Prof. Dr.

julia.welzel@klinikum-augsburg.de

+49 (0) 201 / 723-2431

Bochum, Germany

Status

Recruiting

Address

St. Josef-Hospital - Dermatologische Studienambulanz

Bochum, , 44791

Site Contact

Thilo Gambichler, Prof. Dr.

t.gambichler@klinikum-bochum.de

+49 (0) 201 / 723-2431

Klinikum Dortmund gGmbH - Dermatologie, Dortmund, Germany

Status

Recruiting

Address

Klinikum Dortmund gGmbH - Dermatologie

Dortmund, , 44137

Site Contact

Pia Dücker, Dr. med.

pia.duecker@klinikumdo.de

+49 (0) 201 / 723-2431

Dresden, Germany

Status

Recruiting

Address

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

Dresden, , 01307

Site Contact

Friedegund Meier, Prof. Dr.

friedegund.meier@uniklinikum-dresden.de

+49 (0) 201 / 723-2431

HELIOS Klinikum Erfurt, Erfurt, Germany

Status

Recruiting

Address

HELIOS Klinikum Erfurt

Erfurt, , 99089

Site Contact

Rudolf Herbst, Prof. Dr.

rudolf.herbst@helios-kliniken.de

+49 (0) 201 / 723-2431

Essen, Germany

Status

Recruiting

Address

University Hospital Essen, Department of Dermatology, Skin Cancer Center

Essen, , 45122

Site Contact

Dirk Schadendorf, Prof. Dr.

dirk.schadendorf@uk-essen.de

+49 (0) 201 / 723-2431

Freiburg, Germany

Status

Recruiting

Address

Universitätsklinikum Freiburg - Klinik für Dermatologie und Venerologie

Freiburg, , 79106

Site Contact

Frank Meiß, Dr. med.

frank.meiss@uniklinik-freiburg.de

+49 (0) 201 / 723-2431

Gießen, Germany

Status

Recruiting

Address

Universitätsklinikum Gießen und Marburg GmbH - Klinik für Dermatologie und Allergologie

Gießen, , 35392

Site Contact

Daniela Göppner, PD Dr. med.

daniela.goeppner@derma.med.uni-giessen.de

+49 (0) 201 / 723-2431

Hamburg, Germany

Status

Not yet recruiting

Address

Universitätsklinikum Hamburg-Eppendorf - Hauttumorzentrum

Hamburg, , 20246

Site Contact

Christoffer Gebhardt, Prof. Dr.

ch.gebhardt@uke.de

+49 (0) 201 / 723-2431

Kassel, Germany

Status

Not yet recruiting

Address

Klinikum Kassel GmbH - Klinik für Dermatologie

Kassel, , 34125

Site Contact

Rainer Rompel, Prof. Dr.

rainer.rompel@klinikum-kassel.de

+49 (0) 201 / 723-2431

Kiel, Germany

Status

Recruiting

Address

Universitätsklinikum Schleswig-Holstein, Campus Kiel - Dermatologie

Kiel, , 24105

Site Contact

Axel Hauschild, Prof. Dr.

ahauschild@dermatology.uni-kiel.de

+49 (0) 201 / 723-2431

Leipzig, Germany

Status

Recruiting

Address

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

Leipzig, , 04103

Site Contact

Jan C. Simon, Prof. Dr.

jan.simon@medizin.uni-leipzig.de

+49 (0) 201 / 723-2431

Klinikum Ludwigshafen - Hautklinik, Ludwigshafen, Germany

Status

Recruiting

Address

Klinikum Ludwigshafen - Hautklinik

Ludwigshafen, , 67063

Site Contact

Edgar Dippel, Prof. Dr.

dippele@klilu.de

+49 (0) 201 / 723-2431

Mannheim, Germany

Status

Not yet recruiting

Address

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

Mannheim, , 68167

Site Contact

Jochen S. Utikal, Prof. Dr.

jochen.utikal@umm.de

+49 (0) 201 / 723-2431

München, Germany

Status

Recruiting

Address

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

München, , 80337

Site Contact

Max Schlaak, PD Dr.

Max.Schlaak@med.uni-muenchen.de

+49 (0) 201 / 723-2431

Münster, Germany

Status

Not yet recruiting

Address

Universitätsklinikum Münster - Zentrale Studienkoordination für innovative Dermatologie (ZID)

Münster, , 48149

Site Contact

Carsten Weishaupt, Dr. med.

carsten.weishaupt@ukmuenster.de

+49 (0) 201 / 723-2431

Münster, Germany

Status

Recruiting

Address

Fachklinik Hornheide - Internistische Onkologie

Münster, , 48157

Site Contact

Michael Fluck, Dr. med.

michael.fluck@fachklinik-hornheide.de

+49 (0) 201 / 723-2431

Klinikum Nürnberg Nord - Hautklinik, Nürnberg, Germany

Status

Not yet recruiting

Address

Klinikum Nürnberg Nord - Hautklinik

Nürnberg, , 90419

Site Contact

Dirk Debus, Dr. med.

dirk.debus@klinikum-nuernberg.de

+49 (0) 201 / 723-2431

Quedlinburg, Germany

Status

Recruiting

Address

Harzklinikum Dorothea Christiane Erxleben - Klinik für Dermatologie & Allergologie

Quedlinburg, , 06484

Site Contact

Jens Ulrich, Prof. Dr.

jens.ulrich@harzklinikum.com

+49 (0) 201 / 723-2431

Tübingen, Germany

Status

Recruiting

Address

Universitätsklinikum Tübingen - Dermatoonkologie

Tübingen, , 72076

Site Contact

Thomas K Eigentler, Prof. Dr.

thomas.eigentler@med.uni-tuebingen.de

+49 (0) 201 / 723-2431

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