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

NCT ID: NCT03685890

Last Updated: 2024-04-25

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

74 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-04-01

Study Completion Date

2029-12-31

Brief Summary

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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.

Detailed Description

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Conditions

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Melanoma In-Transit Metastasis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

The study is a randomized placebo controlled double blind trial. Patients will be randomized to ILP with nivolumab or ILP with placebo. Active follow-up for 3 years.
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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ILP + Nivolumab

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

Group Type EXPERIMENTAL

Nivolumab

Intervention Type DRUG

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

Isolated limb perfusion (ILP)

Intervention Type PROCEDURE

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.

ILP + Placebo

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

Group Type PLACEBO_COMPARATOR

Isolated limb perfusion (ILP)

Intervention Type PROCEDURE

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.

Interventions

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Nivolumab

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

Intervention Type DRUG

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.

Intervention Type PROCEDURE

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Vastra Gotaland Region

OTHER_GOV

Sponsor Role lead

Responsible Party

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Roger Olofsson Bagge

Associate professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Netherlands Cancer Institute

Amsterdam, , Netherlands

Site Status RECRUITING

Erasmus MC Cancer Institute

Groningen, , Netherlands

Site Status NOT_YET_RECRUITING

Erasmus MC Cancer Institute

Rotterdam, , Netherlands

Site Status NOT_YET_RECRUITING

Sahlgrenska University Hospital

Gothenburg, , Sweden

Site Status RECRUITING

Countries

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Netherlands Sweden

Central Contacts

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Roger Olofsson Bagge, MD, PhD

Role: CONTACT

+46 31 3428207

Therese Bengtsson

Role: CONTACT

+46 31 3420000

Facility Contacts

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Winan van Houdt, MD, PhD

Role: primary

Lukas Been

Role: primary

Dirk Grünhagen

Role: primary

Roger Olofsson Bagge, Dr

Role: primary

+46 31 3428207

References

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Holmberg CJ, Zijlker LP, Katsarelias D, Huibers AE, Wouters MWJM, Schrage Y, Reijers SJM, van Thienen JV, Grunhagen DJ, Martner A, Nilsson JA, van Akkooi ACJ, Ny L, van Houdt WJ, Olofsson Bagge R. The effect of a single dose of nivolumab prior to isolated limb perfusion for patients with in-transit melanoma metastases: An interim analysis of a phase Ib/II randomized double-blind placebo-controlled trial (NivoILP trial). Eur J Surg Oncol. 2024 Jun;50(6):108265. doi: 10.1016/j.ejso.2024.108265. Epub 2024 Mar 12.

Reference Type RESULT
PMID: 38493679 (View on PubMed)

Tulokas SKA, Kohtamaki LM, Makela SP, Juteau S, Alback A, Vikatmaa PJ, Mattila KE, Skytta TK, Koivunen JP, Tyynela-Korhonen K, Hernberg MM. Isolated limb perfusion with melphalan as treatment for regionally advanced melanoma of the limbs: results of 60 patients treated in Finland during 2007-2018. Melanoma Res. 2021 Oct 1;31(5):456-463. doi: 10.1097/CMR.0000000000000755.

Reference Type DERIVED
PMID: 34132224 (View on PubMed)

Other Identifiers

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SUGBG-KIR-2018-001

Identifier Type: -

Identifier Source: org_study_id

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