A study to test efficacy and safety of nivolumab-treatment in stage II melanoma patients with a high risk of relapse

Phase 1

• Conditions: Stage II melanoma arising from a primary cutaneous site after surgery therapy; MedDRA version: 21.1Level: LLTClassification code 10025655Term: Malignant melanoma of skinSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2019-002276-13-DE
• Lead Sponsor: niversity Hospital Essen, Department of Dermatology

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-08-23
• Last Update Posted: 29 November 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 374

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 < 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).

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

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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified