Investigation of immunotherapy with nivolumab or nivolumab / ipilimumab compared to placebo, respectively, for patients with stage IV melanoma with no evidence of disease after surgery or radiotherapy
- Conditions
- Stage IV melanoma with no evidence of disease after surgery or radiotherapyMedDRA version: 21.1Level: PTClassification code 10025650Term: Malignant melanomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2014-001167-12-DE
- Lead Sponsor
- niversity of Essen
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 167
Patients may be included in the study only if they meet all the following criteria:
1.Stage IV melanoma arising from a primary cutaneous site or metastatic from an unknown primary site with no evidence of disease (NED) after surgery or radiation therapy (conducted within 8 weeks before enrolment)
2.Signed written informed consent
3.Men and women, aged 18 to 80 years
4.Known BRAF status
5.Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other requirements of the study
6.Minimum life expectancy of five years excluding their melanoma diagnosis
7.ECOG performance status of or 1
8.Tumor tissue from the resected site of disease must be provided for biomarker analyses. In order to be randomized a subject must have a PD-L 1 expression classification (positive (= 5% tumor cells expressing PD-L1) or negative (< 5% tumor cells expressing PD-L1)). If an insufficient amount of tumor tissue from the resected site is provided for analysis, acquisition of additional archived tumor tissue (block and/or slides) for the biomarker analyses is required.
9.Prior radiotherapy must have been completed at least 2 weeks prior to study drug administration
10.Screening laboratory values must meet the following criteria and should be obtained within 14 days prior to randomization:
oWBC = 2000/µL
oNeutrophils = 1500/µL
oPlatelets = 100 x103/µL
oHemoglobin = 9.0 g/dL
oSerum creatinine = 1.5xUL
oCreatinine clearance (CrCl) = 40mL/min if using the Cockcroft-Gault formula
Female CrCl = (140 - age in years) x weight in kg x 0.85
72 x serum creatinine in mg/dL
Male CrCl = (140 - age in years) x weight in kg x 1.00
72 x serum creatinine in mg/dL
oAST/ALT = 3 x ULN
oTotal Bilirubin = 1.5 x ULN (except subjects with Gilbert Syndrome, who may have total bilirubin < 3.0 mg/dL)
11.Negative pregnancy test for female subjects and effective contraception (Pearl-Index <1) for both male and female subjects if the risk of conception exists
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 60
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 60
Patients will be excluded from the study for any of the following reasons:
1.History of primary uveal or mucosal melanoma
2.Prior therapy with CTLA4 or PD1 antibodies
3.The patient has psychiatric or addictive disorders that may compromise his/her ability to give informed consent or to comply with the trial procedures.
4.Lack of availability for clinical follow-up assessments.
5.Any immunosuppressive therapy given within the past 30 days prior to study drug administration (excluding physiologic steroid hormone replacement)
6.Other malignancies within the past five years requiring treatment except basal or squamous skin carcinomas or carcinoma in situ of the cervix
7.Serious cardiac, gastrointestinal, hepatic or pulmonary disease reducing life expectancy to less than five years
8.Patients with serious intercurrent illness, requiring hospitalization.
9.Other serious illnesses, e.g., serious infections requiring antibiotics or bleeding disorders.
10.The patient is known to be positive for Human Immunodeficiency Virus (HIV) or other chronic infections (HBV, HCV).or has another confirmed or suspected immunosuppressive or immunodeficient condition.
11.Known hypersensitivity reaction to any of the components of study treatment
12.Pregnancy (absence to be confirmed by ß-HCG serum test, minimum sensitivity 25IU/L or equivalent units of HCG)) or lactation period
13.Women of childbearing potential (WOCBP): Refusal or inability to use effective means of contraception (Pearl-Index <1). WOCBP receiving Nivolumab will be instructed to adhere to contraception until 31 weeks after the last dose of investigational product
14.Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year (Pearl-Index <1). Men receiving Nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception until 31 weeks after the last dose of investigational product
15.Known alcohol or drug abuse
16.Participation in another clinical study and use of any investigational or non-registered product (drug or vaccine) other than the study treatment within the 30 days before registration
17.Significant disease or condition which, in the investigator’s opinion, would exclude the patient from the study
18.Legal incapacity or limited legal capacity
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective of this trial is to estimate the efficacy of adjuvant immunotherapy with Nivolumab alone or in combination with Ipilimumab therapy in stage IV melanoma patients i.e. the primary endpoint is recurrence-free survival (RFS).<br>;Secondary Objective: - Overall survival (OS)<br>- Time to recurrence (TTR)<br>- Progression/recurrence free survival 2 (PRFS2) for crossover patients of Arm C<br>- Safety / toxicity, i.e. all adverse events = Grade 3 according to CTCAE Version 4.0 criteria, that are related to the administration of the investigational agents will be assessed<br>;Primary end point(s): The primary endpoint is recurrence-free survival (RFS);Timepoint(s) of evaluation of this end point: Study enrolment until day of progression/death
- Secondary Outcome Measures
Name Time Method Secondary end point(s): - Overall survival (OS)<br>- Time to recurrence (TTR)<br>- Progression/recurrence free survival 2 (PRFS2) for crossover patients of Arm C<br>- Safety / toxicity, i.e. all adverse events = Grade 3 according to CTCAE Version 4.0 criteria, that are related to the administration of the investigational agents will be assessed;Timepoint(s) of evaluation of this end point: Study enrolment until death/end of study