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

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion 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.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT03685890
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 1/Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Vastra Gotaland Region
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

N/A
Principal Investigator Affiliation N/A
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other
Overall Status Recruiting
Countries Netherlands, Sweden
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Melanoma, In-Transit Metastasis
Arms & Interventions

Arms

Experimental: ILP + Nivolumab

The day before planned ILP, the patient will receive one infusion of nivolumab 480mg

Placebo Comparator: ILP + Placebo

The day before planned ILP, the patient will receive one infusion of placebo

Interventions

Drug: - Nivolumab

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

Procedure: - 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.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

International Sites

Netherlands Cancer Institute, Amsterdam, Netherlands

Status

Recruiting

Address

Netherlands Cancer Institute

Amsterdam, ,

Site Contact

Winan van Houdt, MD, PhD

[email protected]

+46 31 3428207

Erasmus MC Cancer Institute, Groningen, Netherlands

Status

Not yet recruiting

Address

Erasmus MC Cancer Institute

Groningen, ,

Site Contact

Lukas Been

[email protected]

+46 31 3428207

Erasmus MC Cancer Institute, Rotterdam, Netherlands

Status

Not yet recruiting

Address

Erasmus MC Cancer Institute

Rotterdam, ,

Site Contact

Dirk Grünhagen

[email protected]

+46 31 3428207

Sahlgrenska University Hospital, Gothenburg, Sweden

Status

Recruiting

Address

Sahlgrenska University Hospital

Gothenburg, , 413 45

Site Contact

Roger Olofsson Bagge, Dr

[email protected]

+46 31 3428207

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