Evaluating nivolumab with isolated limb perfusion for melanoma patients

A Phase Ib/II Randomized Double-blind Placebo Controlled Trial Evaluating the Effect of Nivolumab for Patients With In-transit Melanoma Metastases Treated With Isolated Limb Perfusion - the NivoILP Trial

This study is testing if combining the immunotherapy drug nivolumab with a special treatment for the arm or leg can help people with advanced melanoma feel better and stay safe during the treatment.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 74 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Vastra Gotaland Region (Government)
• Drugs / interventions: chemotherapy, immunotherapy, prednisone, nivolumab
• Locations: 4 sites (Amsterdam and 3 other locations)
• Trial ID: NCT03685890 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to assess the safety and effectiveness of combining nivolumab, an immunotherapy drug, with isolated limb perfusion (ILP) in patients with in-transit metastases of melanoma. The study will begin with a Phase Ib component involving 20 patients, who will be monitored for at least three months to evaluate safety and efficacy. An independent data safety monitoring board will oversee the trial, ensuring participant safety and making recommendations regarding the continuation of the study into Phase II based on safety findings.

Who should consider this trial

Good fit: Ideal candidates include adults over 18 with confirmed in-transit melanoma metastases and a performance status of 0-2.

Not a fit: Patients with a life expectancy of less than 6 months or those with active cardiac conditions may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could enhance treatment outcomes for patients with in-transit melanoma metastases.

How similar studies have performed: While the combination of nivolumab and ILP is a novel approach, similar immunotherapy strategies have shown promise in treating melanoma.

Eligibility criteria

Inclusion Criteria

1. Male or female aged above 18 years.
2. Signed and dated written informed consent before the start of specific protocol procedures.
3. Histologically or cytologically proven in-transit metastases of malignant melanoma with or without regional lymph node metastases (AJCC v8 stage N1c, N2c and N3c).
4. Measurable disease with at least 1 metastasis measuring at least 5mm
5. ECOG performance status of 0-2

Exclusion Criteria

1. 1\. Life expectancy of less than 6 months
2. Inability to understand given information or undergo study procedures according to protocol.
3. Pregnant or breast-feeding. Women of childbearing potential must have a negative pregnancy test performed within 24 hours before the administration of study drug.
4. Patients must agree to follow instructions for method of contraception for 5 months (women) and 7 months (males) after treatment.
5. Active cardiac conditions, including unstable coronary syndromes (unstable or severe angina, recent myocardial infarction), significant arrhythmias and severe valvular disease that precludes general anaesthesia.
6. History or evidence of clinically significant pulmonary disease e.g., severe COPD that precludes general anesthesia.
7. Reduced renal function defined as S-Creatinine \>=1.5xULN
8. Reduced hepatic function (defined as ASAT, ALAT, bilirubin \>1.5 ULN and PK-INR \>1.5) or a medical history of liver cirrhosis or portal hypertension.
9. Reduced blood leukocytes or platelets defined as a leucocyte count \< 2.0x109/L and thrombocyte count \<100x109/L.
10. Active, autoimmune disease. Subjects are permitted to enrolment if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger.
11. Has evidence of interstitial lung disease or active, non-infectious pneumonitis.
12. A condition requiring systemic treatment with either corticosteroids (\>10 mg daily prednisone equivalents) or other immunosuppressive medications within 30 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses \>10 mg daily prednisone equivalents are permitted.
13. Has an active infection requiring systemic therapy.
14. Has received a live vaccine within 30 days prior to the first dose of trial treatment and 3 months after treatment.
15. Concomitant therapy with any of the following: IL 2 or other non-study immunotherapy regimens; cytotoxic chemotherapy except melphalan (ILP); other investigational therapies within 30 days before trial treatment and 3 months after trial treatment.

Where this trial is running

Amsterdam and 3 other locations

• Netherlands Cancer Institute — Amsterdam, Netherlands (Recruiting)
• Erasmus MC Cancer Institute — Groningen, Netherlands (Not_yet_recruiting)
• Erasmus MC Cancer Institute — Rotterdam, Netherlands (Not_yet_recruiting)
• Sahlgrenska University Hospital — Gothenburg, Sweden (Recruiting)

Study contacts

• Study coordinator: Roger Olofsson Bagge, MD, PhD

Conditions Melanoma; In-Transit Metastasis