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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Vaestra Goetalandsregionen

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

8 Apr 2019 → ongoing

Decision date (initial)

2024-02-19

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Västra Götalandsregionen/Sahlgrenska Universitetssjukhuset

External identifiers

EU CT number

2023-509265-21-00

EudraCT number

2017-004200-21

ClinicalTrials.gov

NCT03685890

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

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, compared to isolated limb perfusion with placebo.

Secondary objectives 9

1. To evaluate time to local progression (TTLP)
2. To evaluate distant metastases-free survival (DMFS)
3. To evaluate progression-free survival (PFS)
4. To evaluate overall survival (OS)
5. To evaluate melanoma-specific survival (MSS)
6. To evaluate safety
7. To evaluate QoL
8. Exploratory objective: To assess changes in immunological parameters during the treatment
9. Exploratory objective: To assess biomarkers for response in tumours and blood

Conditions and MedDRA coding

In-transit metastasis of malignant melanoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Male or female aged above 18 years.
2. Signed and dated written informed consent before the start of specific protocol procedures
3. 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. 4. Measurable disease with at least 1 metastasis measuring at least 5 mm
5. ECOG performance status of 0-2

Exclusion criteria 15

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, described in section 8.4
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. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. CR rate at 3 months after ILP measured according to RECIST 1.1 criteria.

Secondary endpoints 8

1. Time to local progression (TTLP)
2. Distant metastases-free survival (DMFS)
3. Progression-free survival (PFS)
4. Overall survival (OS)
5. Melanoma-specific survival (MSS)
6. Adverse Events (AE) and Serious Adverse Events (SAE)
7. QoL (FACT-M and EQ-5D)
8. The quantitative and qualitative effects of ILP vs. ILP + nivolumab on immune cell phenotypes and function

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Vaestra Goetalandsregionen

Sponsor organisation

Vaestra Goetalandsregionen

Address

Regionens Hus

City

Vänersborg

Postcode

462 80

Country

Sweden

Scientific contact point

Organisation

Vaestra Goetalandsregionen

Contact name

Roger Olofsson Bagge

Public contact point

Organisation

Vaestra Goetalandsregionen

Contact name

Roger Olofsson Bagge

Locations

2 EU/EEA countries · 3 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 12 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications