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MelanomaPhase 1/2MARIANENCT06240143

Intradermal Ipilimumab and Nivolumab in High Risk Stage II Melanoma

A Phase 1/2 study testing Ipilimumab and Nivolumab in people with Melanoma, run by The Netherlands Cancer Institute at 6 sites in Netherlands.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Melanoma
What is being tested?
Ipilimumab and Nivolumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
96 participants
Where
6 sitesNetherlands
Study dates
8 Mar 2024to Mar 2034
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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;
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  • 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;

Who cannot join

  • 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);
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  • 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.

Trial locations and contacts

6 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Christian Blank, Prof contact

+31205129111

c.blank@nki.nl

6 sites in 1 country

Netherlands6 sites, 6 recruiting

  • Amsterdam University Medical Center

    Amsterdam

    Fons van den Eertwegh, Prof.

    Not yet recruiting

  • Antoni van Leeuwenhoek Hospital

    Amsterdam

    Christian Blank, Prof.

    Recruiting

  • University Medical Center Groningen

    Groningen

    Hilde Jalving, Dr.

    Recruiting

  • Leiden University Medical Center

    Leiden

    Ellen Kapiteijn, Dr.

    Not yet recruiting

  • Erasmus University Medical Center

    Rotterdam

    Astrid van der Veldt, Dr.

    Not yet recruiting

  • University Medical Center Utrecht

    Utrecht

    Karijn Suijkerbuijk, Prof.

    Not yet recruiting

Other trials in Netherlands

About this study

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

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
Being tested
Ipilimumab, Nivolumab
Keywords
neoadjuvant, intradermal, immunotherapy, checkpoint inhibitors
Medical subject headings
Melanoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT06240143
Study groupRoleWhat they receive
A: 2x low dose intradermalExperimental2 cycles of intradermal ipilimumab 0.5 mg + nivolumab 1 mg every 3 weeks
Receives: Drug: Ipilimumab; Drug: Nivolumab
B: 6x low dose intradermalExperimental6 cycles of intradermal ipilimumab 0.5 mg + nivolumab 1 mg every week
Receives: Drug: Ipilimumab; Drug: Nivolumab
C: 2x higher dose intradermalExperimental2 cycles of intradermal ipilimumab 10 mg + nivolumab 20 mg every 3 weeks
Receives: Drug: Ipilimumab; Drug: Nivolumab
D: intradermal + intravenousExperimentalintradermal ipilimumab + nivolumab according to the optimal intradermal regimen plus 2 cycles of intravenous nivolumab 240mg every 3 weeks
Receives: Drug: Ipilimumab; Drug: Nivolumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to 100 days after treatment

  2. 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.

    Measured: Up to 5 years after randomization

Secondary outcomes (4)

  1. treatment-related adverse events

    Frequency and duration of all grade and grade 3-5, treatment-related adverse events according to CTCAE 5.0;.

    Measured: Up to 5 years after randomization

  2. EFS

    defined as time from start of treatment to melanoma progression (irresectable stage II or III, or stage IV disease), melanoma recurrence, treatment-related death, or melanoma-related death, whichever occurs first;

    Measured: Up to 5 years after start of treatment

  3. 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;

    Measured: Up to 5 years after randomization

  4. OS

    defined as time between date of start of treatment and date of death;

    Measured: Up to 5 years after start of treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Feb 2024
  2. Study start8 Mar 2024
  3. Primary completionJul 2029 (estimated)
  4. Study completionMar 2034 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
Simon's two-stage design
Masking
None (open label)
Enrolment
96 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06240143
Sponsor's protocol ID
M23MAR
Acronym
MARIANE
Status last verified
Nov 2024
First submitted
25 Jan 2024
Last updated
14 Nov 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Ipilimumab and Nivolumab in people with Melanoma, run by The Netherlands Cancer Institute at 6 sites in Netherlands.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 14 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Christian Blank, Prof (+31205129111, c.blank@nki.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Feasibility of application of studytreatment (time frame: Up to 100 days after treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06240143.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Nov 2024.

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