A Phase 1b/II Study of GDC-0068 or GDC-0980 with Abiraterone Acetate versus Abiraterone Acetate in Patients with Castration-Resistant Prostate Cancer Previously Treated with Docetaxel-Based Chemotherapy (GO27983)
For Phase Ib: -To evaluate how safe and well tolerated GDC-0068 (Akt inhibitor)is when administered in combination with abiraterone and how safe and well tolerated GDC-0980(PI3K/mTOR inhibitor) is when administered in combination with abiraterone - To identify dose-limiting toxicities, estimate the maximum tolerated dose, and identify a recommended Phase II dose of GDC-0068 administered in combination with abiraterone and of GDC-0980 administered in combination with abiraterone For Phase II: -To estimate how well the two combination regimens work when used on prostate cancer patients -To compare the two combination regimens to see whether they work better than abiraterone alone -To evaluate how safe and well tolerated the Recommended Phase 2 Dose (RP2D) of GDC-0068 + abiraterone and prednisone/prednisolone AND how safe and well tolerated the RP2D of GDC-0980 + abiraterone and prednisone/prednisolone are VERSUS placebo + abiraterone and prednisone/prednisolone
For both Phases: -Must be at least 18 years old -Must have confirmed matastatic or advanced prostate adenocarcimona that has been previously treated with docetaxel and has progressed during treatment of at least one hormonal therapy -Must have 2 rising PSA levels at least 2 ng/ml taken at least 1 week apart OR evidence or progession in soft tissue or bone -Must have good physical condition and not require the use of oxygen -Must have good blood, liver and kidney function -Must be able and willing to swallow pills -Must not be a diabetic taking insulin -Must not have heart failure or history of heart attack within 6 months of starting study drug -Must not have Crohn's disease or ulcerative colitis requiring steroids -Must not have significant history of liver disease including current alcohol abuse, cirrhosis or hepatitis -Must not have adrenal insufficiency, hyperaldosteronism -No know HIV infection -No major surgical procedure with 4 weeks of study treatment -Need of steroid therapy of 20 mg or greater -Malignancies other than prostate cancer with 5 years except for adequately treated skin cancers or non-muscle-invasive bladder cancer
Phase I: There are 2 Arms in Phase I -Arm A: 3 patients will be enrolled at a dose level of GDC-0068 400 mg given once a day every day continuously in 28-day treatment cycles. This medication comes in pill form. More patients may be given this dose level if side effects occur and there is a need to assess more patients at this level. After this first group has finished this dose level safely, the dose will increase in a new group of 3 patients to GDC-0068 600 mg. -Arm B: 3 patients will be enrolled at a dose level of GDC-0980 30 mg given once a day every day continuously in 28-day treatment cycles. This medication comes in pill form. More patients may be given this dose level if side effects occur and there is a need to assess more patients at this level. After this first group has finished this dose level safely, the dose will increase in a new group of 3 patients to GDC-0980 40 mg. -For both Arms, the patient will be required to come to the clinic on Days 1, 8 and 15 of the first cycle for assessments including blood work, side effects assessments, questionaires and EKGs. Also, on Days 1 & 15, blood work will be done up to 6 hours after the study drug dose is taken to assess for blood levels of the drug in a patient's system. The patient will also be required to return the next day for additional blood work (Dasy 2 & 16). For the 2nd cycle, the patient must return on Days 1 & 15 for similar assessments. From cycle 3 on, the patient will just be required to come the first day of the cycle. Scans will be performs at the end of Cycles 3,5,7,9 and the every 3 cycles. -Patients may stay on study until when or if disease progression occurs. For Phase II: There are 3 Arms in Phase II -Arm 1: GDC-0068 RP2D (Recommended Phase 2 Dose) + abiraterone 1000 mg once every day + prednisone/prednisolone 5 mg twice a day -Arm 2: GDC-0980 RP2D + abiraterone 1000 mg once every day + prednisone/prednisolone 5 mg twice a day -Arm 3: Placebo + abiraterone 1000 mg once every day + prednisone/prednisolone 5 mg twice a day -These medications are all pills -These medications will be "double-blinded" meaning that neither the staff nor the patient will know which Arm they are receiving. All the study medications will look the same. Only the pharmacy will know which study medications each patient is given. You cannot request to recieve one Arm over another. -Again the medications will be given on a 28 day cycle -The assessments (blood work, side effects assessments, quiestionares, EKGs and study blood work) qre all on the same schedule as Phase I. -Again, patients may stay on study until when or if disease progression occurs.
09/30/2014 04:03 AM