Stage II melanoma arising from a primary cutaneous site after surgery therapy MedDRA version: 21.1 Level: LLT Classification code 10025655 Term: Malignant melanoma of skin System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Opdivo®
Product Name: Nivolumab
Product Code: BMS-936558
Pharmaceutical Form: Concentrate and solvent for solution for infusion
INN or Proposed INN: Nivolumab
CAS Number: 946414-94-4
Curre
Sponsors
University Hospital Essen, Department of Dermatology
Eligibility
Sex/Gender
All
Inclusion 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: o White blood cells (WBC) = 2000/µL o Neutrophils = 1500/µL o Platelets = 100 x103/µL o Hemoglobin = 9.0 g/dL o Serum creatinine = 1.5xUL o Creatinine clearance (CrCl) = 40mL/min (using the Cockcroft-Gault formula) o AST / ALT = 3 x ULN o Total Bilirubin = 1.5 x ULN (except subjects with Gilbert Syndrome, who may have total bilirubin 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). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 250 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 124
Exclusion criteria
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. 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. 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this trial is to determine 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 the date of registration until documented tumor recurrence date or date of death of any cause, whichever occurs first. ;Secondary Objective: Secondary objectives: 1. To evaluate distant metastasis-free survival (DMFS), melanoma-specific survival (MSS) and overall survival (OS) rates at 36 and 60 months 2. Safety / toxicity, i.e. all adverse events = Grade 3 according to CTCAE Version 5.0 criteria, that are definitely, probably, or possibly related to the administration of the investigational agent 3. To evaluate the clinical utility/decision impact of the MelaGenix GEP score in stratifying patients for adjuvant therapy In addition, patients not being selected as high-risk in the biomarker test (= Arm C) and who will be observed as in Arm B will be followed for RFS, DMFS and OS. ;Primary end point(s): Relapse / Recurrence-free survival (RFS) rate ;Timepoint(s) of evaluation of this end point: RFS rate at 36 and 60 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Distant metastasis-free survival (DMFS) rate • Melanoma-specific survival (MSS) rate • Overall survival (OS) rate • AEs and clinical laboratory values • Clinical utility of the MelaGenix GEP score ;Timepoint(s) of evaluation of this end point: • DMFS rate at 36 and 60 months • MSS rate at 36 and 60 months • OS rate at 36 and 60 months | — |
Countries
Germany
Contacts
Public ContactDepartment of Dermatology
University Hospital Essen
Outcome results
None listed