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Closed (no longer recruiting)Last updated: 6 February 2024

NADINA: This phase III study is evaluating the effectiveness of immunotherapy (ipilimumab and nivolumab) followed by the surgical removal of lymph nodes, compared to the standard upfront removal of lymph nodes followed by immunotherapy (nivolumab alone), in people with stage III melanomaMulticenter Phase 3 Trial Comparing Neoadjuvant Ipilimumab Plus Nivolumab Versus Standard Adjuvant Nivolumab in Macroscopic Stage III Melanoma - NADINA

Clinical summary

Summary

Eligible participants will be randomly allocated to either the Experimental Arm or Active Comparator Arm. In the Experimental Arm, participants will receive 2 cycles of neoadjuvant ipilimumab (80mg) and nivolumab (240mg) every 3 weeks, followed by a total lymph node dissection (TLND), and if applicable, surgical removal of in-transit metastases. Participants with a pathologic partial or non-response will also then receive adjuvant nivolumab (480mg) every 4 weeks for 46 weeks. In the case of BRAF V600E/K mutation-positivity, participants with a pathologic partial or non-response will be treated with adjuvant dabrafenib plus trametinib for 46 weeks. In the Active Comparator Arm, participants will receive a standard upfront TLND, and if applicable, surgical removal of in-transit metastases, followed by 12 cycles of adjuvant nivolumab (480mg) every 4 weeks. All study participants will be treated until melanoma progression to irresectable stage III or stage IV disease, disease recurrence, unacceptable toxicity, participant withdrawal of consent or until the end of study treatment.

Conditions

This trial is treating patients with stage III melanoma

Cancer

Skin Cancers Skin

Age

People16+

Phase

III

Trial Acronym

NADINA

More information

Trial Identifiers

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Trial sponsor

Bristol-Myers Squibb (BMS),Netherlands Cancer Institute

Scientific Title

Multicenter Phase 3 Trial Comparing Neoadjuvant Ipilimumab Plus Nivolumab Versus Standard Adjuvant Nivolumab in Macroscopic Stage III Melanoma - NADINA

Eligibility

Inclusion

  • 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 a palpable node, confirmed as melanoma by pathology, or a non-palpable but enlarged lymph node according to RECISTv1.1 (at least 15 mm in short axis), confirmed as melanoma by pathology, or 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 or PD-L1;
  • 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 for 23 weeks post last ipilimumab + nivolumab infusion;
  • Males who are sexually active with 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 for 31 weeks post last ipilimumab + nivolumab infusion;
  • 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 recurrence, and other requirements of the study;
  • Patient has signed the Informed Consent document.

Exclusion

  • Distantly metastasized melanoma;
  • Uveal/ocular or mucosal melanoma;
  • In-transit metastases only (without cytological or histological proven lymph node involvement)
  • 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 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;
  • 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 components 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.

Inclusion

  • Your cancer has spread to other parts of the body.

Exclusion

  • You have been diagnosed with a prior or secondary type of cancer.
  • You have certain types of non-cancer medical conditions.
  • You have had certain treatments, surgical procedures or drugs.
  • You have previously been treated (or are currently being treated) on a clinical trial.
Message

Clinical trials have complex eligibility criteria.

Ask your doctor if this trial could be right for you.

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