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MelanomaPhase 1/2NivoILPNCT03685890

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

A Phase 1/2 study testing Nivolumab and Isolated limb perfusion (ILP) in people with Melanoma and In-Transit Metastasis, run by Vastra Gotaland Region at 4 sites in 2 countries.

Recruiting

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

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Melanoma, In-Transit Metastasis
What is being tested?
Nivolumab and Isolated limb perfusion (ILP)
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
74 participants
Where
4 sitesin 2 countries
Study dates
1 Apr 2019to 31 Dec 2029
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

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

Who cannot join

  • 1. Life expectancy of less than 6 months
  • Inability to understand given information or undergo study procedures according to protocol.
  • Pregnant or breast-feeding. Women of childbearing potential must have a negative pregnancy test performed within 24 hours before the administration of study drug.
  • Patients must agree to follow instructions for method of contraception for 5 months (women) and 7 months (males) after treatment.
  • Active cardiac conditions, including unstable coronary syndromes (unstable or severe angina, recent myocardial infarction), significant arrhythmias and severe valvular disease that precludes general anaesthesia.
  • History or evidence of clinically significant pulmonary disease e.g., severe COPD that precludes general anesthesia.
Show all 15Show fewer
  • Reduced renal function defined as S-Creatinine >=1.5xULN
  • 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.
  • Reduced blood leukocytes or platelets defined as a leucocyte count < 2.0x109/L and thrombocyte count <100x109/L.
  • 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.
  • Has evidence of interstitial lung disease or active, non-infectious pneumonitis.
  • 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.
  • Has an active infection requiring systemic therapy.
  • Has received a live vaccine within 30 days prior to the first dose of trial treatment and 3 months after treatment.
  • 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 locations and contacts

4 sites in 2 countries. Contact the study team or a site near you to ask about taking part.

Roger Olofsson Bagge, MD, PhD contact

+46 31 3428207

roger.olofsson.bagge@gu.se

Therese Bengtsson contact

+46 31 3420000

therese.bengtsson@vgregion.se

4 sites in 2 countries

Netherlands3 sites, 3 recruiting

  • Netherlands Cancer Institute

    Amsterdam

    Winan van Houdt, MD, PhD

    Winan van Houdt, MD, PhD

    Recruiting

  • Erasmus MC Cancer Institute

    Groningen

    Lukas Been

    Lukas Been, Md, PhD

    Not yet recruiting

  • Erasmus MC Cancer Institute

    Rotterdam

    Dirk Grünhagen

    Dirk Grünhagen, MD, PhD

    Not yet recruiting

Other trials in Netherlands

Sweden1 site, 1 recruiting

  • Sahlgrenska University Hospital

    Gothenburg, 413 45

    Roger Olofsson Bagge, Dr, +46 31 3428207, roger.olofsson.bagge@gu.se

    Roger Olofsson Bagge, Dr

    Recruiting

Other trials in Sweden

About this study

Official title: 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

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.

Being tested
Nivolumab, Isolated limb perfusion (ILP)
Medical subject headings
Melanoma

What participants receive

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

  • NivolumabDrug

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

  • Isolated limb perfusion (ILP)Procedure or surgery

    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 groups in NCT03685890
Study groupRoleWhat they receive
ILP + NivolumabExperimentalThe day before planned ILP, the patient will receive one infusion of nivolumab 480mg
Receives: Drug: Nivolumab; Procedure: Isolated limb perfusion (ILP)
ILP + PlaceboPlacebo comparatorThe day before planned ILP, the patient will receive one infusion of placebo
Receives: Procedure: Isolated limb perfusion (ILP)

What is being measured

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

  1. Complete response rate (CR)

    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.

    Measured: 3 months

Secondary outcomes (7)

  1. Time to local progression (TTLP)

    Evaluation of local progression-free survival (LPFS). LPFS is defined as the number of months from the date of ILP to the date of the first documented disease recurrence or progression in the treated area (defined as the area below the tourniquet used for ILP). LPFS will be determined based on clinical assessments according to RECIST version 1.1 criteria.

    Measured: 36 months

  2. Distant metastases-free survival (DMFS)

    Evaluation of DMFS, defined as the number of months from the date of ILP to the date of the first documented distant disease recurrence.

    Measured: 36 months

  3. Progression-free survival (PFS)

    Evaluation of PFS, defined as the number of months from the date of ILP to the date of the first documented disease recurrence or progression at any site.

    Measured: 36 months

  4. Melanoma specific survival (MSS)

    Evaluation of melanoma specific survival (MSS), MSS is calculated as the time from date of treatment to date of death due to any cause. Both median MSS and the per cent of patients alive at 36 months will be evaluated.

    Measured: 36 months

  5. Overall survival (OS)

    Evaluation of overall survival (OS), OS is calculated as the time from date of treatment to date of death due to any cause. Both median OS and the per cent of patients alive at 36 months will be evaluated.

    Measured: 36 months

  6. Quality of life measured by FACT-M

    Quality of life (QoL) by FACT-M. Change from baseline for all subscales as well as for the total scores.

    Measured: 36 months

  7. Quality of life measured by EQ-5D

    Quality of life (QoL) by EQ-5D measured as the change from baseline

    Measured: 36 months

Timeline

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

  1. First posted26 Sep 2018
  2. Study start1 Apr 2019
  3. Primary completion31 Dec 2026 (estimated)
  4. Study completion31 Dec 2029 (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
Randomised
Intervention model
Parallel groups
Model description
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.
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
74 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03685890
Sponsor's protocol ID
SUGBG-KIR-2018-001
Acronym
NivoILP
Status last verified
Apr 2024
First submitted
23 Sep 2018
Last updated
25 Apr 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 38493679

  • Constantinescu A, Olofsson Bagge R, Huibers A. Immunological phenotype as a predictor for response after isolated limb perfusion for patients with melanoma in-transit metastasis. Eur J Surg Oncol. 2026 Mar;52(3):111424. doi: 10.1016/j.ejso.2026.111424. Epub 2026 Jan 23.

    PubMed 41616426

  • 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.

    PubMed 34132224

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Nivolumab and Isolated limb perfusion (ILP) in people with Melanoma and In-Transit Metastasis, run by Vastra Gotaland Region at 4 sites in 2 countries.

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 5 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 25 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in Netherlands, Sweden. 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. Some participants in this study may receive a placebo. 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 Roger Olofsson Bagge, MD, PhD (+46 31 3428207, roger.olofsson.bagge@gu.se), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Complete response rate (CR) (time frame: 3 months). 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 NCT03685890, which also lists 3 linked publications.

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 25 Apr 2024.

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