A Dose Finding Pharmacokinetic Study of the Tumour-targeting Human L19IL2 Monoclonal Antibody-Cytokine Fusion Protein in Patients With Advanced Solid Tumours
This is a Phase I/II study for patients with solid tumors and renal cell carcinoma (RCC; for the Phase II part). L19-IL2 is a tumor targeted immunocytokine constituted of a single chain Fragment variable (scFv) format directed against the ED-B domain of fibronectin, one of the most important markers for neoangiogenesis, and the human cytokine interleukin-2 (IL2).
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Dose Finding Pharmacokinetic Study of the Tumour-targeting Human L19IL2 Monoclonal Antibody-Cytokine Fusion Protein in Patients With Advanced Solid Tumours|
- To determine the maximum tolerated dose (MTD) and recommended dose (RD) of the human L19IL2 fusion-cytokine. [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]
- To determine the pharmacokinetic profile. [ Time Frame: 5 days ] [ Designated as safety issue: No ]
- To determine the qualitative and quantitative toxicity profile. [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]
- To assess the presence of anti-fusion protein antibodies in treated patients. [ Time Frame: 18 weeks ] [ Designated as safety issue: Yes ]
- To evaluate the safety profile of repeated administrations of L19IL2 in patients treated at the RD. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
- To identify early signs of antitumour activity. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
|Study Start Date:||November 2005|
|Study Completion Date:||November 2009|
|Primary Completion Date:||April 2008 (Final data collection date for primary outcome measure)|
Route: i.v. infusion (60 min) Patients will receive a minimum of 2 cycles of treatment. Each cycle is comprised of treatment on Days 1, 3 and 5 followed by a 16 days rest (1 cycle= 21 days). Patients may receive up to 4 further cycles of treatment (max. of 6 cycles in total). Patients will be initially recruited into the study in cohorts of 3 and the starting dose of L19IL2 will be 5 Mio IU IL2 equivalent. Five steps of dose escalation are planned: 5, 10, 20, 30 and 40 Mio IU IL2 equivalent). After the MTD has been established, the RD will be determined. A further 12 patients (with RCC) will receive the RD dose for a minimum of 2 cycles. For patients in the RD part of the study, patients can switch to maintenance therapy. Maintenance therapy consists of 15 Mio IU IL2 every 2 weeks. The maximum duration of the study for a patient is 12 months.
This is an open-label, non-randomised, multicentre, Phase I/II study to assess safety, pharmacokinetics (PK), and early signs of activity of L19-IL2 monotherapy.
In the first part of the study, there will be 5 dose escalation steps in sequential cohorts of patients with advanced solid tumours. In the second part of the study, patients with advanced RCC will be given a fixed dose of L19IL2 at the RD.
|Campus Charité Mitte|
|Berlin, Germany, 10117|
|European Institute of Oncology|
|Milan, Italy, 20141|
|Principal Investigator:||Filippo De Braud, Dr||European Institute of Oncology Milan (Italy)|
|Principal Investigator:||Manfred Johannsen, Dr||Champus Charitè Mitte Berlin (Germany)|