Combination Therapy of F16IL2 and Doxorubicin in Solid Tumour Patients
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.
Advanced Solid Tumor
Drug: F16IL2 in combination with doxorubicin
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||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|
- Maximum tolerated and recommended dose (MTD) (RD) [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]Phase I: To establish the maximum tolerated dose (MTD) and the RD of F16IL2 when administered in combination with doxorubicin.
- Efficacy of F16IL2 in combination with doxorubicin [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]Phase II: To investigate the efficacy in terms of objective response rate of F16IL2 in combination with doxorubicin in breast cancer patients amenable to anthracyclin therapy.
- Safety/Tolerability [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]Phase I/II: To investigate the safety, tolerability of F16IL2 and doxorubicin when given as a combination
- Pharmacokinetics of F16IL2 [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]Phase I: To investigate pharmacokinetics of F16IL2 and doxorubicin when given as a combination.
- Human anti-fusion protein antibodies [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]Phase I: To investigate the induction of human anti-fusion protein antibodies (HAFA).
- Antitumor activity [ Time Frame: 12 months ] [ Designated as safety issue: No ]To investigate the antitumor activity of the combination of F16IL2 and doxorubicin in solid tumour patients.
- Median progression-free survival [ Time Frame: 12 months ] [ Designated as safety issue: No ]For phase II to assess median progression-free survival of F16IL2 in combination with doxorubicin
- Median overall survival [ Time Frame: 12 months ] [ Designated as safety issue: No ]For phase II to assess median overall survival of F16IL2 in combination with doxorubicin
|Study Start Date:||June 2008|
|Estimated Study Completion Date:||March 2013|
|Primary Completion Date:||March 2012 (Final data collection date for primary outcome measure)|
|Experimental: F16IL2 in combination with doxorubicin||
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.
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).
|A.O. UNIVERSITARIA OSPEDALI RIUNITI - OSPEDALE UMBERTO I DI ANCONA - ANCONA (AN) (Italy)|
|Irst - Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori - Meldola (Fc)|
|European Institute of Oncology|
|A.O. UNIVERSITARIA POLICLINICO DI MODENA (Italy)|
|Azienda Ospedaliera Universitaria Senese|
|Principal Investigator:||Chiara Matilde Catania, Dr||European Institute of Oncology Milan, Italy|