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.
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
29
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)
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)
National Cancer Institute (NCI)
Bethesda, Maryland, United States
Dana Farber/Harvard Cancer Center, Dana Farber Cancer Institute
Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States
Massachusetts General Hospital
Cambridge, Massachusetts, United States
Part 1: To assess the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and safety of GC1008 in patients with locally advanced or metastatic renal cell carcinoma or malignant melanoma.
Time frame: up to 2.5 years
Part 1: To assess dose-limiting toxicity of GC1008 in patients with locally advanced metastatic renal cell carcinoma or malignant melanoma.
Time frame: up to 2.5 years
Part 1: To assess the safety of GC1008 in patients with locally advanced or metastatic renal cell carcinoma or malignant melanoma.
Time frame: up to 2.5
Part 2: To assess the safety of GC1008 following multiple doses at 15 mg/kg (or 10 mg/kg depending on the safety review of the first cohort of 6 patients at 15 mg/kg) in patients with locally advanced or metastatic malignant melanoma.
Time frame: Up to 2 years
Part 1 & 2: To assess possible surrogate markers that might predict clinical efficacy by obtaining skin (part 2), tumor and blood samples for exploratory biomarker analyses.
Time frame: up to 2.5 years
Part 1 & 2: To obtain pharmacokinetic (PK) and pharmacodynamic (PD) data on GC1008.
Time frame: up to 2.5 years
Part 1 & 2: To evaluate tumor response as a preliminary assessment of clinical activity.
Time frame: up to 2.5 years
Part 2: To evaluate the relationship between GC1008 exposure, clinical response, and the development of skin lesions.
Time frame: Up to 2 years
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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)
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)
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)
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)
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)
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)
Cancer Institute of New Jersey
New Brunswick, New Jersey, United States
Ohio State University
Columbus, Ohio, United States