Multicenter phase 3 trial comparing NeoADjuvant Ipilimumab + Nivolumab versus standard Adjuvant nivolumab in macroscopic stage III melanoma - NADINA
- Conditions
- melanomaskin cancer10040900
- Registration Number
- NL-OMON54313
- Lead Sponsor
- Antoni van Leeuwenhoek Ziekenhuis
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 150
• Men and women, at least 16 years of age;
• World Health Organization (WHO) Performance Status 0 or 1;
• Cytologically or histologically confirmed resectable stage III melanoma of
cutaneous or unknown primary origin with one or more macroscopic lymph node
metastases (clinical detectable), that can be biopsied and a maximum of 3
additional resectable in-transit metastases. A concurrent resectable primary
melanoma is allowed. Clinical detectable lymph nodes are defined as either:
o a palpable node, confirmed as melanoma by pathology,or;
o a non-palpable but enlarged lymph node according to RECISTv1.1 (at least 15
mm in short axis), confirmed as melanoma by pathology, or;
o a PET scan positive lymph node of any size confirmed as melanoma by pathology;
• No other malignancies, except adequately treated and with a cancer-related
life-expectancy of more than 5 years;
• No prior immunotherapy targeting CTLA-4, PD-1, PD-L1 or LAG-3;
• No prior targeted therapy targeting BRAF and/or MEK;
• No immunosuppressive medications within 6 months prior study inclusion
(steroids equivalent to prednisolone <=10 mg are allowed);
• Screening laboratory values must meet the following criteria: WBC >=2.0x109/L,
neutrophils >=1.5x109/L, platelets >=100x109/L, hemoglobin >=5.5 mmol/L,
creatinine <=1.5xupper limit of normal (ULN), AST <=1.5x ULN, ALT <=1.5x ULN,
bilirubin <=1.5x ULN (except for subjects with Gilbert syndrome who must have a
total bilirubin <3.0 mg/dL);
• LDH level <1.5x ULN;
• Women of childbearing potential (WOCP) must use appropriate method(s) of
contraception, i.e. methods with a failure rate of <1% per year when used
consistently and correctly, to avoid pregnancy during and until 23 weeks post
last ipilimumab + nivolumab infusion;
• Males who are sexually active with WOCP are not required to use contraception
during treatment with nivolumab +/- ipilimumab, but must use appropriate
method(s) of contraception, i.e. methods with a failure rate of <1% per year
when used consistently and correctly, to avoid pregnancy during and until 17
weeks post last dabrafenib + trametinib administration;
• Patient willing and able to understand the protocol requirements and comply
with the treatment schedule, scheduled visits, electronic patient outcome
reporting, tumor biopsies and extra blood withdrawal during screening and in
case of relapse, and other requirements of the study;
• Patient has signed the Informed Consent document.
• Distantly metastasized melanoma;
• Uveal/ocular or mucosal melanoma;
• Subjects with any active autoimmune disease or a documented history of
autoimmune disease, or history of syndrome that required systemic steroids or
immunosuppressive medications. Subjects with vitiligo, resolved childhood
asthma/atopy type I diabetes mellitus, residual hypothyroidism due to
autoimmune thyroiditis only requiring hormone replacement, skin disorders (such
as vitiligo, psoriasis, or alopecia) not requiring systemic treatment are
permitted to enroll;
• Prior radiotherapy; targeting the affected lymph node region(s);
• Subjects will be excluded if they test positive for hepatitis B virus surface
antigen (HBsAg) or hepatitis C virus ribonucleic acid (HCV antibody),
indicating acute or chronic infection. Subjects treated and being at least one
year free from HCV are allowed to participate;
• Subjects will be excluded if they have known history of testing positive for
human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome
(AIDS);
• Subjects with history of allergy to study drug compononents or history of
severe hypersensitivity reaction to monoclonal antibodies.
• Subjects with underlying medical conditions or active infection that, in the
investigator's opinion, will make the administration of study drug hazardous or
obscure the interpretation of toxicity or adverse events;
• Women who are pregnant or breastfeeding;
• Concurrent medical condition requiring the use of immunosuppressive
medications, or immunosuppressive doses of systemic or absorbable topical
corticosteroids >10 mg prednisolone daily equivalent;
• Use of other investigational drugs before study drug administration 30 days
or 5 half-times before study inclusion;
• Psychological, familial, sociological, or geographical conditions that
potentially hamper compliance with the study protocol and follow-up schedule;
those conditions should be discussed with the subject before registration in
the trial.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary endpoint:<br /><br>• EFS, defined as time from randomization to melanoma progression (irresectable<br /><br>stage III or stage IV disease), melanoma recurrence, treatment-related death,<br /><br>or melanoma-related death, whichever occurs first.</p><br>
- Secondary Outcome Measures
Name Time Method