Clinical trial NCT03685890: Evaluating the Effect of Nivolumab for Patients With In-transit Metastases Treated With Isolated Limb Perfusion
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Melanoma
In-Transit Metastasis
Lead sponsor: Vastra Gotaland Region
Sponsor class: OTHER_GOV
First posted: 2018-09-26
Enrollment: 74
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

Brief 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 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.

Primary outcomes:
measure: Complete response rate (CR)
timeFrame: 3 months
Secondary outcomes:
measure: Time to local progression (TTLP)
timeFrame: 36 months
measure: Distant metastases-free survival (DMFS)
timeFrame: 36 months
measure: Progression-free survival (PFS)
timeFrame: 36 months
measure: Melanoma specific survival (MSS)
timeFrame: 36 months
measure: Overall survival (OS)
timeFrame: 36 months
measure: Quality of life measured by FACT-M
timeFrame: 36 months
measure: Quality of life measured by EQ-5D
timeFrame: 36 months
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: Netherlands Cancer Institute
city: Groningen
country: Netherlands
facility: Erasmus MC Cancer Institute
city: Rotterdam
country: Netherlands
facility: Erasmus MC Cancer Institute
city: Gothenburg
country: Sweden
facility: Sahlgrenska University Hospital
Study officials:
References:
citation: 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.
citation: 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.