NIVOLUMAB for Stage II cutaneous melanoma

Inclusion criteria

• {"criterion_text":"- Histologically confirmed diagnosis of stage II (AJCCv8) melanoma arising from a primary cutaneous site after surgery therapy\n- Screening laboratory values must meet the following criteria and should be obtained within 14 days prior to registration: o White blood cells (WBC) ≥ 2000/μL o Neutrophils ≥ 1500/μL o Platelets ≥ 100 x10^3/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)\n- 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 folliclestimulating hormone (FSH) levels ≥ 40 IU/L.\n- 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).\n- Sentinel node biopsy without detection of melanoma deposits\n- Registration not later than 12 weeks after SNB procedure\n- Tumor tissue from primary tumor must be provided for biomarker analyses. In order to be registered, a patient must be classified by MelaGenix risk analysis.\n- Men and women at the age of 18 to 80 years\n- Signed written, informed consent\n- Patients must be willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other requirements of the study\n- Minimum life expectancy of five years excluding their melanoma diagnosis\n- ECOG performance status of 0-1"}

Exclusion criteria

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

Primary endpoints

• {"endpoint_text":"- Relapse / Recurrence-free survival (RFS) will be analyzed by stratified Cox regression. 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.","definition_or_measurement_approach":"Primary endpoint measured as Relapse-Free Survival (RFS): time from date of registration until documented tumor recurrence date or date of death from any cause, whichever occurs first; analysis planned by stratified Cox regression."}

Secondary endpoints

• {"endpoint_text":"- RFS rate","definition_or_measurement_approach":"RFS rate to be evaluated at 12, 24, 36 and 60 months (per secondary objectives)."}
• {"endpoint_text":"- Distant metastasis-free survival (DMFS) rate","definition_or_measurement_approach":"DMFS rate to be evaluated at 12, 24, 36 and 60 months."}
• {"endpoint_text":"- Melanoma-specific survival (MSS) rate","definition_or_measurement_approach":"MSS rate to be evaluated at 12, 24, 36 and 60 months."}
• {"endpoint_text":"- Overall survival (OS) rate","definition_or_measurement_approach":"OS rate to be evaluated at 12, 24, 36 and 60 months."}
• {"endpoint_text":"- AEs and clinical laboratory values","definition_or_measurement_approach":"Safety/toxicity measured as all adverse events ≥ Grade 3 according to CTCAE Version 5.0 criteria that are definitely, probably, or possibly related to the investigational agent; clinical laboratory assessments per protocol."}
• {"endpoint_text":"- Clinical utility of the MelaGenix GEP score","definition_or_measurement_approach":"Assessment of the clinical utility/decision impact of the MelaGenix gene expression profile (GEP) score in stratifying patients for adjuvant therapy; patients not selected as high-risk by the assay (Arm C) will be followed for outcomes to evaluate assay utility."}

Germany

Earliest CTIS Part Ii Submission Date

29-05-2024

Latest Decision Or Authorization Date

06-03-2026

Processing Time Days

646

Number Of Sites

20

Number Of Participants

423

Primary sponsor

Full Name

Universitaetsklinikum Essen AöR

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Germany

Third parties

• {"country":"Germany","full_name":"Universitaetsklinikum Essen AöR","duties_or_roles":"codes: 1,10,11,12,2,6,7,8,9","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Germany","full_name":"Alcedis GmbH","duties_or_roles":"codes: 1,10,11,12,2,5,6,7,8,9","organisation_type":"Pharmaceutical company"}