AMG-479 in Treating Patients With Advanced Solid Tumors or Non-Hodgkin Lymphoma
RATIONALE: Monoclonal antibodies, such as AMG-479, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them.
PURPOSE: This phase I trial is studying the side effects and best dose of AMG-479 in treating patients with advanced solid tumors or non-Hodgkin lymphoma.
Small Intestine Cancer
Unspecified Adult Solid Tumor, Protocol Specific
Other: laboratory biomarker analysis
Other: pharmacological study
|Study Design:||Allocation: Randomized
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 1, Open-Label, Dose Finding Study Evaluating the Safety and Pharmacokinetics of AMG 479 in Subjects With Advanced Solid Tumors|
- Safety [ Designated as safety issue: Yes ]
- Pharmacokinetic profile [ Designated as safety issue: No ]
- Level of insulin-like growth factor receptor-1 (IGF-1R) on peripheral blood cells [ Designated as safety issue: No ]
- Tumor response measured by modified RECIST [ Designated as safety issue: No ]
- Tumor glucose metabolism as measured by fludeoxyglucose F 18-PET/CT scan [ Designated as safety issue: No ]
- Anti-AMG-479 antibody formation [ Designated as safety issue: No ]
- The incidence of dose-limiting toxicities and the severity of adverse events [ Designated as safety issue: Yes ]
- Levels of cross-linked c-telopeptides of type 1 collagen and bone-specific alkaline phosphatase (may also include tartrate-resistant acid phosphatase 5b) in blood [ Designated as safety issue: No ]
- Circulating levels of IGF-1R and IGF-BP3 [ Designated as safety issue: No ]
|Study Start Date:||October 2005|
|Study Completion Date:||June 2010|
|Primary Completion Date:||April 2010 (Final data collection date for primary outcome measure)|
- To assess the safety and pharmacokinetics of anti-IGF-1R fully human monoclonal antibody AMG-479 (AMG-479) after multiple intravenous administrations in adult patients with histologically documented advanced solid tumors that are refractory to standard therapy or for which no curative therapy is available.
- To assess the tolerability and to determine the maximum tolerated dose of AMG-479.
- To assess tumor glucose metabolism using PET/CT scanning with the tracer fludeoxyglucose F 18.
- To measure insulin-like growth factor receptor (IGF-1R) levels on peripheral blood cells.
- To establish whether human anti-human antibodies to AMG-479 develop in patients with advanced solid tumors.
- To measure the tumor response by modified Response Evaluation Criteria in Solid Tumors.
- To investigate bone turnover markers.
- To investigate potential biomarker development by biochemical analysis in blood cells and tumor cells.
OUTLINE: This is a multicenter study.
- Part 1 (dose-escalation): Patients receive escalating doses of anti-IGF-1R fully human monoclonal antibody AMG-479 (AMG-479) IV over 1 hour on days 1, 15, and 29. Patients are evaluated in week 8, and those who demonstrate an objective tumor response or stable disease continue treatment beginning on day 57. Treatment with AMG-479 repeats every 2 weeks in the absence of disease progression or unacceptable toxicity.
Part 2 (randomized dose-expansion): Patients are randomized to one of two dose regimens.
- Arm I: Patients receive AMG-479 IV over 1 hour at a lower dose on day 1.
- Arm II: Patients receive AMG-479 IV over 1 hour at a higher dose on day 1. Treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity. Tumor tissue is obtained at baseline and after 4 weeks of study therapy for biomarker analysis.
Blood is drawn periodically for biomarker analysis (insulin-like growth factor [IGF]-1, IGF-binding protein 3 [IGF-BP3], IGF-1 receptor [IGF-1R], cross-linked c-telopeptides of type 1 collagen [CTx], bone-specific alkaline phosphatase [BSAP], and tartrate-resistant acid phosphatase [TRAP5b]) and pharmacokinetic studies.
After completion of study therapy, patients are followed for at least 4 weeks.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00562380
|United States, Tennessee|
|Vanderbilt-Ingram Cancer Center|
|Nashville, Tennessee, United States, 37232-6838|
|Study Chair:||Mace L. Rothenberg, MD, FACP||Vanderbilt-Ingram Cancer Center|