NCT00356460

Safety and Efficacy Study of GC1008 to Treat Renal Cell Carcinoma or Malignant Melanoma

A Phase 1 Study of the Safety and Efficacy of GC1008: A Human Anti Transforming Growth Factor-beta (TGFβ) Monoclonal Antibody in Patients With Advanced Renal Cell Carcinoma or Malignant Melanoma

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 29 (actual)
• Sponsor: Genzyme, a Sanofi Company · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to determine the safety, tolerability, pharmacokinetics and pharmacodynamics of GC1008, a human anti-transforming growth factor-beta (TGFβ) monoclonal antibody in previously treated patients with locally advanced or metastatic renal cell carcinoma or malignant melanoma.

Detailed description

Transforming growth factor-beta (TGFβ) is a cytokine which is often over-expressed and over-produced by malignancies and has been implicated as an important factor in promoting the growth, progression, and metastatic potential of advanced cancers. In preclinical studies, TGFβ can act to promote tumor cell migration/invasiveness, influence tumor stroma (by increasing extracellular matrix production, cytokine secretion, and angiogenesis), and suppress anti-tumor immunity. The purpose of this study is to investigate the clinical use of GC1008, a human monoclonal antibody capable of binding and neutralizing all isoforms of TGFβ. This is a Phase 1 multi-center, open-label, dose-escalation study designed to characterize the safety, tolerability, pharmacokinetic, pharmacodynamic, and potential anti-tumor activity of GC1008, in patients with histologically confirmed, locally advanced and surgically inoperable or metastatic renal cell carcinoma (RCC) or malignant melanoma. Patients with RCC must have failed at least 1 prior therapy and patients with renal cell carcinoma must have failed either sorafenib or sunitinib. Other qualifying prior therapies includes any medical, surgical, radiation or investigational approaches used for potential therapeutic benefit (but not for diagnostic purposes) in patients with advanced disease. Patients may receive up to 4 intravenous infusions of GC1008, and patients with stable disease, with an objective tumor response or with clinical benefit may be eligible to receive extended therapy. For part 2 of the study, only patients with malignant melanoma will be enrolled.

Conditions

• Carcinoma, Renal Cell
• Melanoma

Interventions

Type	Name	Description
BIOLOGICAL	GC1008 Human Anti Transforming Growth Factor _Beta (TGFβ) Monoclonal Antibody	1 dose of 0.1 mg/kg IV followed by a 28 day observation period and then 3 additional doses of 0.1 mg/kg IV (one dose every 14 days)
BIOLOGICAL	GC1008 Human Anti Transforming Growth Factor _Beta (TGFβ) Monoclonal Antibody	1 dose of 0.3 mg/kg IV followed by a 28 day observation period and then 3 additional doses of 0.3 mg/kg IV (one dose every 14 days)
BIOLOGICAL	GC1008 Human Anti Transforming Growth Factor _Beta (TGFβ) Monoclonal Antibody	1 dose of 1.0 mg/kg IV followed by a 28 day observation period and then 3 additional doses of 1.0 mg/kg IV (one dose every 14 days)
BIOLOGICAL	GC1008 Human Anti Transforming Growth Factor _Beta (TGFβ) Monoclonal Antibody	1 dose of 3.0 mg/kg IV followed by a 28 day observation period and then 3 additional doses of 3.0 mg/kg IV (one dose every 14 days)
BIOLOGICAL	GC1008 Human Anti Transforming Growth Factor _Beta (TGFβ) Monoclonal Antibody	1 dose of 10.0 mg/kg IV followed by a 28 day observation period and then 3 additional doses of 10.0 mg/kg IV (one dose every 14 days)
BIOLOGICAL	GC1008 Human Anti Transforming Growth Factor _Beta (TGFβ) Monoclonal Antibody	1 dose of 15.0 mg/kg IV followed by a 28 day observation period and then 3 additional doses of 15.0 mg/kg IV (one dose every 14 days)
BIOLOGICAL	GC1008 Human Anti Transforming Growth Factor _Beta (TGFβ ) Monoclonal Antibody	1 dose of 15.0 mg/kg IV followed by a 28 day observation period and then 3 additional doses of 15.0 mg/kg IV (one dose every 14 days)
BIOLOGICAL	GC1008 Human Anti Transforming Growth Factor _Beta (TGFβ) Monoclonal Antibody	1 dose of 15.0 or 10.0 mg/kg IV (based on safety profile of part 2, cohort 1) followed by a 28 day observation period and then 3 additional doses of 15.0 or 10.0 mg/kg IV (one dose every 14 days)

Timeline

• Start date: 2006-09-01
• Primary completion: 2009-05-01
• Completion: 2009-05-01
• First posted: 2006-07-26
• Last updated: 2014-03-19

Locations

6 sites across 1 country: United States