Intratumoral Administration of L19IL2/L19TNF
This Phase II study is an uncontrolled, multicenter, prospective study for patients with malignant melanoma of the skin in clinical stage III or stage IV M1a.
Twenty Patients will be treated with a mixture of L19IL2 and L19TNF once weekly for up to 4 weeks.
The dose will be distributed among the lesions via multiple intralesional injections.
The proportion of patients with complete response at week 12 will be calculated.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Study of Intratumoral Application of L19IL2/L19TNF in Melanoma Patients in Clinical Stage III or Stage IV M1a With Presence of Injectable Cutaneous and/or Subcutaneous Lesions|
- Rate of patients with complete response (CR) of L19IL2 treated Index/Non-Index lesions at week 12. [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
- Efficacy of L19IL2/L19TNF treated Index/non treated lesions [ Time Frame: week 12, 24 and 36 ] [ Designated as safety issue: No ]
- Rate of patients with CR, PR and SD of all metastases at week 12, 24 and 36 (objective response rate according to RECIST v 1.1)
- Duration of objective response and disease control of all metastases
- Median overall survival (mOS)
- Overall survival (OS) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
- Safety of the combination treatment with L19IL2 and L19TNF [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]Evaluation of the type and the number of adverse events eventually present
|Study Start Date:||December 2012|
|Estimated Study Completion Date:||December 2014|
|Estimated Primary Completion Date:||October 2014 (Final data collection date for primary outcome measure)|
Experimental: L19IL2 + L19TNF
One arm, intratumoral injections of 10 Mio IU of L19IL2 and 312 μg L19TNF. Weekly administration for all combined leasions
Patients will be treated with intratumoral injections of 10 MioIU L19IL2 and 312μg L19TNF once weekly for up to 4 weeks.
L19IL2 is a recombinant fusion protein composed of a fully human recombinant monoclonal antibody (L19) and the human recombinant interleukin-2 (IL-2).
IL2, is a potent stimulator of the immune response. It has a central role in the regulation of T cell responses and effects on other immune cells such as natural killer cells, B cells, monocyte/macrophages and neutrophils. IL2 can induce tumor regression through its ability to stimulate a potent cell-mediated immune response in vivo.
L19TNF is a recombinant fusion protein composed of a fully human recombinant monoclonal antibody (L19) and the human tumor necrosis factor-alpha, a primary mediator of immune regulation and inflammation.
As an anti-tumor agent, TNF exerts its major effects via a preferential toxicity for the endothelial cells of the tumor-associated vasculature and an increase of the antitumor immune response. Given at sufficient doses (e.g. intratumorally or in the ILP setting with melphalan), TNF causes significant tumor shrinkage in solid cancer subjects.
This phase II signal generating study is designed to test the efficacy and safety of an intratumorally administered mixture of L19IL2 + L19TNF in patients suffering from metastatic melanoma. It is well documented that the intratumoral administration of IL-2 leads to a high response rate and unexpectedly favorable longtime outcome and several tumor responses have been observed in clinical trials of Philogen, both using intratumorally administered L19IL2 and L19TNF in the ILP setting.
Preclinical data produced within the Philogen group now suggest that the intratumoral administration of a mixture of L19IL2 and L19TNF could be even more effective. After only one intratumoral administration of a mixture of L19IL2 and L19TNF tumors disappeared completely while neither L19IL2 nor L19TNF monotherapy was nearly as effective.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02076633
|Contact: Leonardo Giovannoni, Dr||(0039) 0577- 588 firstname.lastname@example.org|
|Fondazione IRCCS Istituto Nazionale dei Tumori||Recruiting|
|Contact: Mario Santinami, Dr|
|Principal Investigator: Mario Santinami, Dr|
|Azienda Ospedaliera Universitaria Senese||Recruiting|
|Contact: Michele Maio, Dr.|
|Principal Investigator: Michele Maio, Dr|
|Principal Investigator:||Mario Santinami, Dr||Fondazione IRCCS Istituto Nazionale dei Tumori|