Study of GemOx and Vandetanib in Advanced Solid Malignancy
This is a research study that will try to find the highest and safest dose of an experimental drug, vandetanib, that can be given in combination with two standard chemotherapy agents, gemcitabine and oxaliplatin, to subjects with advanced solid malignancies.
Advanced Incurable Solid Malignancy
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||An Open Label Phase I Study of Gemcitabine/Oxaliplatin (GEMOX) and Vandetanib (ZACTIMA; ZD6474) Combination in Patients With Advanced Solid Malignancy (IRUSZACT0070) (UPCI 07-025)|
- To establish the Maximum Tolerated Dose (MTD) and toxicities of vandetanib (Zactima; ZD6474) in combination with fixed dose of GEMOX (gemcitabine/oxaliplatin) and to establish the recommended phase II dose of the GEMOX and vandetanib regimen [ Time Frame: The MTD (and recommended phase II dose) is defined as the highest dose at which <2 of 6 patients experience DLT. The observation period for DLT is the first cycle of therapy. ] [ Designated as safety issue: Yes ]
- To document clinical responses and to identify time to progression (TTP) of each patient compared to TTP on prior therapy [ Time Frame: Radiologic imaging is done every 6-7 weeks for disease assessment ] [ Designated as safety issue: Yes ]
|Study Start Date:||February 2009|
|Estimated Study Completion Date:||October 2013|
|Primary Completion Date:||December 2010 (Final data collection date for primary outcome measure)|
All subjects receive the same combination study drug and follow the same study schedule. As a phase 1 study, only the doses will vary between subjects.
Vandetanib is a pill that will be self-administered orally on Days 1-14 of each 14-day cycle. The dose of vandetanib each subject will receive will be determined by a dose escalation schedule (either 200 mg or 300 mg per day), which will be followed to determine the MTD of the study drug combination (vandetanib + GemOx). In the absence of disease progression, unacceptable toxicities, or other complications, the vandetanib and GemOx combination may continue per protocol for a maximum of 6 cycles, or 12 weeks. In subjects who show response or stable disease, vandetanib may be continued as a single agent beyond the 6 cycle maximum, at the investigator's discretion.
Other Names:Drug: Gemcitabine
30-minute IV infusion of 1000 mg/m^2 gemcitabine on Day 1 of each 14-day cycle.
Other Name: Gemzar®Drug: Oxaliplatin
Immediately following gemcitabine IV: 2-hour IV infusion of 85 mg/m^2 oxaliplatin on Day 1 of each 14-day cycle.
Other Name: Eloxatin®
This is a Phase I, open-label, dose-escalating, non-randomized study of the safety and tolerability of vandetanib in combination with a fixed dose of gemcitabine and oxaliplatin (GemOx) in the treatment of patients with advanced solid malignancy. EGFR is an important target for therapeutic drug development. It is widely expressed in most cancers and has a vital role in the regulation of proliferation signals. EGFR is expressed in a high degree (>80%) of pancreatic tumors and is a rational target for therapy. Vandetanib selectively inhibits EGFR tyrosine kinase activity and VEGF-2 receptor. It has good oral bioavailability and has growth inhibitory activity in a wide variety of human cell lines including cells with acquired resistance to other EGFR inhibitors. The growth inhibitory property of vandetanib in vivo correlates more with its anti VEGF property, especially in cell lines with acquired resistance to EGFR inhibition. The combination of gemcitabine and oxaliplatin (GEMOX) is a well-established regimen that has demonstrated encouraging antitumor activity in pancreaticobiliary cancers in phase II studies. Recent clinical trials have also shown activity in hepatobiliary and germ cell tumors. The combination of vandetanib and gemcitabine has potential advantages and may result in an additive or synergistic effect. The GEMOX regimen is well tolerated, and toxicity does not overlap with the most common toxicity of rash or diarrhea observed with vandetanib. Thus, the combination of vandetanib and GEMOX is expected to be a well tolerated, and an easily administered regimen with improved efficacy and no overlapping toxicities.
|United States, Pennsylvania|
|University of Pittsburgh Cancer Institute / Hillman Cancer Center|
|Pittsburgh, Pennsylvania, United States, 15232|
|Principal Investigator:||Leonard J. Appleman, M.D., Ph.D.||University of Pittsburgh|