NCT01055522

Clinical Study Phase II of L19IL2 in Combination With Dacarbazine in Patients With Metastatic Melanoma

Dose Definition and Activity Evaluation Study of the Tumor-Targeting Human L19IL2 Monoclonal Antibody-Cytokine Fusion Protein in Combination With Dacarbazine in Patients With Metastatic Melanoma

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 102 (actual)
• Sponsor: Philogen S.p.A. · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This Phase II clinical study is an open-label, multicenter study of L19IL2 in combination with Dacarbazine in patients with metastatic melanoma. The study is divided in two parts: a phase IIa part, designed to establish the recommended dose (RD) of L19IL2 when administered in combination with a fixed dose of Dacarbazine, as well as to determine the preliminary tolerability profile; the second phase IIb part evaluates the objective response rate (ORR) including a randomized study with a fixed dose of Dacarbazine with or without L19IL2, dosed at the RD determined in phase IIa.

Detailed description

Dose limiting toxicity will be assessed during the dose-escalation part of Phase IIa from day 1 through day 21 of the first cycle. Response will be measured using RECIST criteria every 6 weeks (after every 2 cycles of treatment). Patients with stable or responding disease at each assessment may receive additional treatment for a maximum of 6 cycles of induction. Patients with stable or responding disease after induction may receive L19IL2 (without dacarbazine) every 2 weeks as maintenance therapy. Tumor expression of ED-B FN and tumor uptake of L19IL2 and of Dacarbazine will be assessed via immunohistochemistry and/or other methods deemed appropriate on tumor tissue biopsies. Tumor biopsy will be performed on superficial accessible cutaneous and/or subcutaneous lesions only. Tumor biopsy will be considered optional and will not preclude patient entry on to study should the patient refuse. Pharmacokinetics of L19IL2, Dacarbazine and AIC will be assessed from serial blood samples using standard methods. Overall response rate, PFS, survival rate at 6 and 12 months, and overall survival time for all patients and separately for the patients in the Phase IIb part will be assessed using standard methods.

Conditions

• Metastatic Melanoma

Interventions

Type	Name	Description
DRUG	Arm 1: L19IL2 + Dacarbazine	RD of L19IL2 determined in phase IIa. Induction Phase A: Intravenous (IV) infusion of L19IL2 on days 1, 3 and 5 of each 21-day cycle over 60 minutes via automated device (perfusor), for four consecutive 21-day cycles. Induction Phase B: Intravenous (IV) infusion of L19IL2 on days 1, 8 and 15 of each 21-day cycle over 60 minutes via automated device (perfusor), for four consecutive 21-day cycles. Maintenance: Intravenous (IV) infusion of L19IL2 on days 1, 8 and 15 of each 21-day cycle over 60 minutes via automated device (perfusor), for a maximum of 1 year after start of treatment. DTIC 1,000mg/m2 every three weeks until disease progression, unacceptable toxicity, withdrawal of consent, or one year from initiation of therapy, whichever occurs first
DRUG	Arm 3: Dacarbazine	Dacarbazine Dosage: 1,000 mg/m2 DTIC every three weeks until disease progression, unacceptable toxicity, withdrawal of consent, or for a maximum of 8 cycles, whichever occurs first.
DRUG	ARM 2: L19IL2 + Dacarbazine	RD of L19IL2 determined in phase IIa. Intravenous (IV) infusion of L19IL2 on days 1, 8 and 15 of each 21-day cycle over 60 minutes via automated device (perfusor), for for a maximum of 1 year after start of treatment. DTIC 1,000mg/m2 every three weeks until disease progression, unacceptable toxicity, withdrawal of consent, or one year from initiation of therapy, whichever occurs first

Timeline

• Start date: 2008-06-01
• Primary completion: 2013-02-01
• Completion: 2014-02-01
• First posted: 2010-01-25
• Last updated: 2014-02-25

Locations

10 sites across 4 countries: Austria, Germany, Italy, Switzerland