A Phase 1, Open-Label, Dose Finding Study Evaluating the Safety and Pharmacokinetics of AMG 479 in Subjects With Advanced Solid Tumors
- 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
- 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
- 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.
Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment
Mace L. Rothenberg, MD, FACP
Vanderbilt-Ingram Cancer Center
United States: Food and Drug Administration
|Vanderbilt-Ingram Cancer Center||Nashville, Tennessee 37232-6838|