Ireland
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Recruiting Phase 1/2

Evaluating the Effect of Nivolumab for Patients With In-transit Metastases Treated With Isolated Limb Perfusion

NCT03685890 · tracked via the Priya Life Science Netherlands tracker
Phase
Phase 1/2
Started
2019-04-01
Last updated
2024-04-25

Condition(s) studied

MelanomaIn-Transit Metastasis

Investigational drug(s) / intervention(s)

Nivolumab →Isolated limb perfusion (ILP)

Nivolumab: One infusion of nivolumab (Opdivo®) 480mg (flat dose) in NaCl (Natriumklorid Baxter Viaflo, 9 mg/ml) during 60 minutes

Isolated limb perfusion (ILP): Patients will be treated with ILP according to clinical routine at each separate site. The procedure is performed under general anaesthesia. The major artery and vein of the limb is catheterized, and a tourniquet is placed proximally on the limb. Continuous leakage monitoring is performed. The perfusate is heated to 40C and after ensuring steady state, melphalan (Alkeran®) at a dose of 13 mg/L (upper limb) or 10 mg/L (lower limb) is infused into the circulation during 20 minutes for a total perfusion time of 60 minutes. According to local routine tasonermin (Beromun®) will be added to the perfusate 30 minutes before the melphalan as a bolus dose of 1-4 mg.

Study summary

To evaluate safety and the effect of isolated limb perfusion together with nivolumab as a way to increase efficacy and give further insights in early immunological mechanisms.

In the first phase Ib part, 20 patients will be enrolled and followed for a minimum of 3 months. An independent data safety monitoring board (DSMB) will continuously review safety and judge the seriousness of the events and also recommend the study to stop if necessary. If the DSMB do not find safety issues, the trial will continue as a phase II trial.

Eligibility

Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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.

Primary outcome measure(s)

  • Complete response rate (CR) — 3 months
    To evaluate if melphalan based isolated limb perfusion (ILP) synergizes with nivolumab in inducing complete responses (CR) at 3 months after treatment in melanoma patients with in-transit metastasis.

Trial sites (4)

FacilityCityRegionStatus
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

More Vastra Gotaland Region trials in the Netherlands

Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT03685890 on ClinicalTrials.gov ↗ ← All trials in the Netherlands