Intradermal Ipilimumab and Nivolumab in High Risk Stage II Melanoma

NCT06240143 | Recruiting Phase 1 DMC

• 1 other identifier: M23MAR
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 6

Brief 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.

Conditions

Melanoma

Keywords

neoadjuvant; intradermal; immunotherapy; checkpoint inhibitors

Outcome Measures

Primary Outcomes (2)

• Feasibility of application of studytreatment

  Feasibility as measured by the adherence to the timelines in the study protocol. A treatment arm will be declared as not feasible if 3/11 or 6/24 patients cannot adhere to the planned time of surgery due to treatment-related adverse events.

  Up to 100 days after treatment

• Rate of effectiveness of the studytreatment

  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 Outcomes (4)

• treatment-related adverse events

  Up to 5 years after randomization

• EFS

  Up to 5 years after start of treatment

• DMFS

  Up to 5 years after randomization

• OS

  Up to 5 years after start of treatment

Study Arms (4)

A: 2x low dose intradermal

EXPERIMENTAL

2 cycles of intradermal ipilimumab 0.5 mg + nivolumab 1 mg every 3 weeks

Drug: Ipilimumab; Drug: Nivolumab

B: 6x low dose intradermal

EXPERIMENTAL

6 cycles of intradermal ipilimumab 0.5 mg + nivolumab 1 mg every week

Drug: Ipilimumab; Drug: Nivolumab

C: 2x higher dose intradermal

EXPERIMENTAL

2 cycles of intradermal ipilimumab 10 mg + nivolumab 20 mg every 3 weeks

Drug: Ipilimumab; Drug: Nivolumab

D: intradermal + intravenous

EXPERIMENTAL

intradermal ipilimumab + nivolumab according to the optimal intradermal regimen plus 2 cycles of intravenous nivolumab 240mg every 3 weeks

Drug: Ipilimumab; Drug: Nivolumab

Interventions

Ipilimumab DRUG

intradermal

A: 2x low dose intradermal; B: 6x low dose intradermal; C: 2x higher dose intradermal; D: intradermal + intravenous

Nivolumab DRUG

intradermal

A: 2x low dose intradermal; B: 6x low dose intradermal; C: 2x higher dose intradermal; D: intradermal + intravenous

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women, at least 18 years of age;
• World Health Organization (WHO) Performance Status 0 or 1;
• Histologically confirmed, stage pT3-4 cutaneous melanoma (Breslow thickness \>2.0mm; according to AJCC criteria 8th edition);
• Having ≥44% 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 prior immunotherapy targeting CTLA-4, PD-1, PD-L1 or LAG-3;
• No prior targeted therapy with BRAF/MEK inhibition;
• 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;

You may not qualify if:

• Acral, uveal/ocular, mucosal or or lentigo maligna 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;
• 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.

Sponsors & Collaborators

• The Netherlands Cancer Institute: lead

Study Sites (6)

Amsterdam University Medical Center

Amsterdam, Netherlands

NOT YET RECRUITING

Antoni van Leeuwenhoek Hospital

Amsterdam, Netherlands

RECRUITING

University Medical Center Groningen

Groningen, Netherlands

RECRUITING

Leiden University Medical Center

Leiden, Netherlands

NOT YET RECRUITING

Erasmus University Medical Center

Rotterdam, Netherlands

NOT YET RECRUITING

University Medical Center Utrecht

Utrecht, Netherlands

NOT YET RECRUITING

MeSH Terms

Conditions

Melanoma

Interventions

Ipilimumab; Nivolumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Christian Blank, Prof

  Medical oncologist/researcher

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Christian Blank, Prof

CONTACT

+31205129111; c.blank@nki.nl

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Simon's two-stage design

Study Record Dates

• First Submitted: January 25, 2024
• First Posted: February 2, 2024
• Study Start: March 8, 2024
• Primary Completion (Estimated): July 1, 2029
• Study Completion (Estimated): March 1, 2034
• Last Updated: November 14, 2024

Record last verified: 2024-11

Locations

NL (6)