NCT01131364

Combination Therapy of F16IL2 and Doxorubicin in Solid Tumour Patients

A Dose-finding, Pharmacokinetic, Phase Ib/II Study of the Tumour-targeting Human F16IL2 Monoclonal Antibody-cytokine Fusion Protein in Combination With Doxorubicin in Patients With Advanced Solid Tumours

• Status: Terminated
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 29 (actual)
• Sponsor: Philogen S.p.A. · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This Phase Ib/II study is an openlabel, multicenter study for patients with solid tumors and breast cancer amenable to anthracyclin therapy. The study is divided in two parts: Phase I: an open-label, dose escalation study of F16IL2 in combination with doxorubicin for patients with solid tumors. Phase II: a prospective, single-arm, multicentre study of a fixed dose of F16IL2 in combination with doxorubicin, equivalent to stage 1 of the Simon two-stage phase II design, for patients with breast cancer amenable to anthracyclin therapy.

Detailed description

Breast cancer is a major cause of cancer mortality, second only to lung cancer as a cause of cancer death in women. The five-year survival rate for localized breast cancer has increased from 80 percent in the 1950s to 98 percent today. However, the mortality rate in the most advanced forms remains unsatisfactory. Indeed, the extensive use of mammography within screening programs has led to cancers being detected earlier, when early treatments may be more effective. A greater understanding of the molecular biology and genetic expression of breast cancer has therefore led to new pre-surgical and post-surgical treatments, including hormone modulators and monoclonal antibodies. Many of these agents have led to decreased mortality and disease recurrence. F16 is a human recombinant antibody fragment in the scFv (single chain Fragment variable) format that is directed against tenascin C, an angiogenesis marker common to most solid tumors independent of the tumor type. ScFv(F16) selectively localizes in tumor tissues in animal models as demonstrated both histologically and during mechanistic studies involving mice transfected with orthotopic human tumours. IL2, the human cytokine interleukin-2, 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 (Smith, 1988). IL2 can induce tumor regression through its ability to stimulate a potent cell-mediated immune response in vivo (Rosenberg, 2000).

Conditions

• Advanced Solid Tumor
• Breast Cancer

Interventions

Type	Name	Description
DRUG	F16IL2 in combination with doxorubicin	Intravenous (i.v.) infusions of F16IL2 (Dose escalation: from 5 up to 25 MioIU) on days 1, 8, 15, 29, 36 and 43 over 60 minutes via automated device (perfusor), followed by a 30-minute i.v. infusion of doxorubicin (Dose escalation: from 20 up to 25 mg/m2) on Days 1, 8, 15 29, 36 and 43. Patients with objective tumor responses or stable disease will receive repeated cycles of treatment starting on Day 56. Patients will receive additional cycles of combination therapy for a maximum of 6 months, or until disease progression, unacceptable toxicity or withdrawal of consent.

Timeline

• Start date: 2008-06-01
• Primary completion: 2012-03-01
• Completion: 2012-12-01
• First posted: 2010-05-26
• Last updated: 2014-02-25

Locations

5 sites across 1 country: Italy