A Phase Ib, Open-Label, Dose-Escalation Study Evaluating the Safety, Tolerability and Pharmacokinetics of GDC-0973 in Combination with GDC-0941 When Administered in Patients with Locally advanced or Metastatic Solid Tumors. (Protocol MEK4752g)
The study is being done to help us best learn how to use new drugs that may be effective treatments for cancer. The objectives are to evaluate the safety and tolerability of the combination of GDC-0973 and GDC-0941 in patients with locally advanced or metastatic solid tumors, determine the maximal tolerated dose (MTD), and identify a recommended dose and schedule for Phase II studies.
- advanced solid tumor that is refractory to standard treatment - evaluable disease or measurable disease per RECIST - good performance status and be able to swallow pills - good organ and blood functions - provide archival tumor tissue - no prior treatment ending toxicity from MEK or P13K pathway inhibitors - no diabetes requiring daily medication - no condition requiring anticoagulants with exceptions of thrombolytics for venous catheters patency and prophylactic anticoagulation for venous access devices - treated brain metastasis, stable for at least 4 weeks and off glucocorticoids - no history of retinal vein occlusion of central serous retinopathy - no treatment with known strong substrates or inhibitors of CYP3A 4/5 and substrates of CYP2D6. Subjects in the indication specific expansion cohorts must: - have had 4 or less prior therapies for locally advanced or metastatic cancer - measurable disease - have diagnosis of pancreatic adenocarcinoma, KRAS mutant non small cell lung cancer (NSCLC), KRAS colorectal carcinoma, KRAS mutant endometriod cancer or KRAS mutant endometriod cancer arising from endometriosis, or EGFR T790M mutant, EGFR inhibitor-progressing NSCLC - agree to have tumor biopsies done pre and post treatment
Outpatient regimen of two oral medications taken together. The two oral medications are self administered in one of three schedules during a 28-day treatment cycle. The first schedule is the consecutive schedule; both drugs are taken together daily for 21 consecutive days followed by 7 days of no drug. The second schedule is intermittent schedule; drugs are taken together on Days 1,4,8,11,15, and 18 of each 28-day cycle. The third schedule is 7/7 schedule; drugs are taken together daily on Days 1-7 and Days 12-21 of each 28 day cycle. No drugs are taken on Days 8-15 or Days 22-28. Subjects self administer GDC-0973 and GDC-0941 pills on an empty stomach. Subjects fast, except for water, for one hour before or four hours after a meal. Subject continues until intolerable toxicity or disease progresses. Dose escalating cohorts continue until the maximally tolerated dose and dose limiting toxicities are determined. Subjects are seen at least weekly for the first 2 cycles. Thereafter, they are seen at the end of each cycle for evaluation prior to the start of the next cycle of treatment. Radiologic measurements are to be done after every second cycle.
05/24/2013 04:02 AM