Intradermal Ipilimumab and Nivolumab in High Risk Stage II Melanoma

Melanoma Clinical Trial

— MARIANE  

Official title:

Multicenter Phase 1b/2 Trial Testing Neoadjuvant Intradermal Ipilimumab and Nivolumab in High Risk Stage II Melanoma - MARIANE

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06240143
• Other study ID #: M23MAR
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• Start date: February 2024
• Est. completion date: May 2026

Study information

• Verified date: January 2024
• Source: The Netherlands Cancer Institute
• Contact: Christian Blank, Prof
• Phone: +31205129111
• Email: c.blank[@]nki.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This open label, single country trial will test if local injection of low-dose ipilimumab and nivolumab, is safe and reduces the sentinel node positivity in high-risk stage II melanoma patients.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 80
• Est. completion date: May 2026
• Est. primary completion date: February 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Men and women, at least 18 years of age;
• World Health Organization (WHO) Performance Status 0 or 1;
• Histologically confirmed, excised stage IIB or IIC cutaneous melanoma (Breslow thickness 2.1-4.0mm with ulceration, or Breslow thickness >4.0mm with or without ulceration; according to AJCC criteria 8th edition);
• Having =50% risk for SN positivity as assessed by the MIA Sentinel Node Metastasis Risk prediction tool (melanomarisk.org.au/SNLForm)1;
• Excision of primary melanoma took place =4 weeks prior to informed consent;
• Naïve for re-excision of the primary melanoma site and for sentinel node procedure;
• No other solid, distantly metastasized malignancies, no hematological malignancies and no malignancies for which systemic treatment is administered within 6 months prior to study inclusion;
• No prior immunotherapy targeting CTLA-4, PD-1, PD-L1 or LAG-3;
• No prior targeted therapy with BRAF/MEK inhibition;
• No immunosuppressive medications within 6 months prior to 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 =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;
• 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 other requirements of the study;

Exclusion Criteria:

• Acral, uveal/ocular or mucosal melanoma;
• A concurrent second, primary melanoma;
• Regionally or distantly metastasized melanoma, including in-transit metastases and macroscopic lymph node metastases;
• No suspect lymph nodes detectable by ultrasound in the draining lymph node region(s);
• 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 surgery, including prior sentinel node procedure or lymph node dissection, in the affected lymph node region(s);
• 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 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.

Related Conditions & MeSH terms

• Melanoma

Intervention

Drug:
• Ipilimumab
intradermal
• Nivolumab
intradermal
• Nivolumab
intravenous

Locations

Country	Name	City	State
Netherlands	Amsterdam University Medical Center	Amsterdam
Netherlands	Antoni van Leeuwenhoek Hospital	Amsterdam
Netherlands	University Medical Center Groningen	Groningen
Netherlands	Leiden University Medical Center	Leiden
Netherlands	Erasmus University Medical Center	Rotterdam
Netherlands	University Medical Center Utrecht	Utrecht

Sponsors (1)

Lead Sponsor	Collaborator
The Netherlands Cancer Institute

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Feasibility	Feasibility as measured by the adherence to the timelines in the study protocol. A treatment arm will be declared as not feasible if 2/7 or 5/20 patients cannot adhere to the planned time of surgery due to treatment-related adverse events.	Up to 100 days after treatment
Primary	Effectivity	Pathological response as assessed by blinded central review, adapted from the INMC criteria, including pCR, near-pCR, or pPR (0-50% residual viable tumor in resection material), or sentinel node negativity for melanoma.	Up to 5 years after randomization
Secondary	treatment-related adverse events	Frequency and duration of all grade and grade 3-5, treatment-related adverse events according to CTCAE 5.0;.	Up to 5 years after randomization
Secondary	EFS	defined as time from randomization to melanoma progression (irresectable stage II or III, or stage IV disease), melanoma recurrence, treatment-related death, or melanoma-related death, whichever occurs first;	Up to 5 years after randomization
Secondary	DMFS	defined as time between date of surgery (re-excision and SN-procedure) and date of first distant metastasis, treatment-related death or melanoma-related death, whichever occurs first;	Up to 5 years after randomization
Secondary	OS	defined as time between date of randomization and date of death;	Up to 5 years after randomization