Phase 1 Dose-finding Study of L19TNFα Plus Melphalan Using Isolated Inferior Limb Perfusion (ILP) in Subjects With Intransit Stage III/IV Melanoma
In this study the recombinant human fusion protein L19TNFα will be associated in ILP with the standard treatment with melphalan 10mg/l limb volume in subjects affected by stage III/IV limb melanoma.
The recombinant human fusion protein L19TNFα was created with the intention to target TNFα directly to tumor tissues with the result in high and sustained intralesional bioactive TNFα concentrations.
|Patients With Intransit Stage III/IV Melanoma of Lower Extremity Distal to the Apex of the Femoral Triangle.||Other: Isolated inferior limb perfusion||Phase 1|
|Study Design:||Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase 1 Dose-finding Study of Tumor-targeting Human Monoclonal Antibody-cytokine Fusion Protein L19TNFα Plus Melphalan Using Isolated Inferior Limb Perfusion in Patients With In-transit Stage III/IV Melanoma.|
- Safety and Tolerability [ Time Frame: 6 weeks ]The safety and tolerability profile of L19TNFα/melphalan combination treatment in the ILP setting will be determined.
- Recommended dose (RD) [ Time Frame: 29 days ]The recommended dose (RD) of L19TNFα when given in combination with melphalan in the ILP setting for subjects with limb stage III/IV melanoma will be determined.
- Objective response rate [ Time Frame: 10 weeks ]Objective response rate of L19TNFα plus melphalan.
- Antitumor activity [ Time Frame: 4- 6 weeks ]Antitumor activity of L19TNFα plus melphalan (resection of residual tumor after 4- 6 weeks and histopathological response rate).
- Pharmacokinetic [ Time Frame: 10 days ]Pharmacokinetic profile of L19TNFα when given with melphalan
- Human anti-fusion protein antibody [ Time Frame: 6 weeks ]Assessment of possible induction of human anti-fusion protein antibody [HAFA] formation
- 5-hydroxyindoleacetic acid [ Time Frame: 10 days ]Assessment of plasma profile of 5-hydroxyindoleacetic acid (5-HIAA), a surrogate marker of vascular damage and tumor response.
|Study Start Date:||October 2008|
|Study Completion Date:||September 2011|
|Primary Completion Date:||March 2011 (Final data collection date for primary outcome measure)|
Experimental: L19TNFα plus melphalan
Subjects will be sequentially assigned to one of 2 dose levels of L19TNFα: 325 µg or 650 µg. All subjects will receive a single dose of L19TNFα and Melfalan (10mg/ L Limb volume).
Other: Isolated inferior limb perfusion
Single Melphalan bolus perfused for 60 min after 30 min of L19TNFα bolus. Intra-arterial (IA) infusion via bolus at 39˚C to 40˚C (mild hyperthermia).
Please refer to this study by its ClinicalTrials.gov identifier: NCT01213732
|Azienda Ospedaliera Universitaria San Martino|
|Fondazione IRCCS Istituto Nazionale dei Tumori|
|Principal Investigator:||Franco De Cian, Prof||IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy|