This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Previous studies have shown that erlotinib is well tolerated at the 150 mg daily dose but that erlotinib as a single agent has not demonstrated significant clinical activity in metastatic colorectal cancer. This study will evaluate the safety, efficacy, and pharmacodynamic effects of the combination of erlotinib and modified FOLFOX6 (mFOLFOX6) for treatment of metastatic colorectal cancer. During Cycle 1, subjects will take 150 mg erlotinib in tablet form daily. Patients who have not developed a grade 2 rash by Days 14-16, and have no drug-related toxicity of grade 2 or higher, will have their dose of erlotinib increased to 200 mg daily. For patients who undergo escalation of erlotinib to 200 mg daily, Cycle 2 will consist of 14 days of single agent erlotinib at 200 mg daily and then mFOLFOX6 chemotherapy will begin in Cycle 3. For patients who do not undergo escalation of the erlotinib dose, Cycle 2 will consist of erlotinib at 150 mg daily plus mFOLFOX6 as detailed in the protocol. FOLXFOX6 chemotherapy consists of a combination of oxaliplatin, leucovorin, and 5-fluorouracil infused over 46 hours and repeated every 2 weeks. Subjects will have tumor and skin biopsies prior to Day 1 and once again between Days 14-16. Pharmacokinetic samples for steady-state trough erlotinib and metabolite OSI-420 concentration will be drawn on Day 8, on Day 14-16 after the biopsy, and again 4 days after the mFOLFOX6 chemotherapy has started. Disease assessment will take place after every 4 cycles of mFOLFOX6. Patients may continue on treatment until disease progression or unacceptable toxicity. The study involves 2 study sites and will enroll 20 subjects. 10 subjects are expected at this site. Subjects will have pharmacokinetic samples drawn on an outpatient basis, and recover from biopsies as in inpatient at the GCRC.
Showing the most recent 10 out of 753 publications
