A phaseIb/II study of GDC-0068 or GDC-0980 in patients with CRPC

• Research type

  Research Study

• Full title

  A PHASE Ib/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

• IRAS ID

  99732

• Contact name

  Johann S de Bono

• Sponsor organisation

  Genentech, Inc

• Eudract number

  2011-004126-10

• Clinicaltrials.gov Identifier

  NCT01485861

• Research summary

  Research Summary
  This is a phase Ib/II study of GDC-0068 or GDC-0980 with abiraterone in patients with castration-resistant prostate cancer (CRPC) previously treated with docetaxel-based chemotherapy. The study is funded by Genentech, Inc. Despite the success of previous abiraterone studies, CRPC remains an incurable disease with limited progression-free and overall survival. The purpose of this study is to evaluate whether combined inhibition of androgen signaling (with abiraterone) and PIK3/Akt signaling (with GDC-0068 or GDC-0980) is safe and will improve the efficacy of single-agent abiraterone in patients with CRPC. This trial consists of two stages: ?½ A Phase Ib, open-label stage in which the recommended Phase II dose (RP2D) will be determined for GDC-0068 and GDC-0980 in combination with abiraterone 1000 mg daily and prednisolone 5 mg twice daily. ?½ A Phase II, double-blind, randomized comparison of GDC-0068 or GDC-0980 with abiraterone and prednisolone versus placebo with abiraterone and prednisolone. About 258 patients from approximately 70 sites in the US and Europe will take part in this study, with approximately 30 patients expected in the UK. Patients will receive study treatment until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination. The length of the study will differ for each patient but the study will require a maximum of 30 study visits over a period up to approximately 2 years. The study involves procedures including physical exams, vital signs, electrocardiograms, blood tests, urine tests, CT, MRI and bone scans, and patient questionnaires."

  Lay summary of study results:
  Ipatasertib was well tolerated and safety data were consistent with the known safety profile.
  The safety data were consistent with those reported previously in the Update CSR. No new safety signals were identified.
  Ipatasertib and M1 metabolite exposures were increased when administered in combination with prednisone/prednisolone and abiraterone. Glucose profiles (average glucose, peak glucose and % time in range) were increased for ipatasertib when administered in combination with prednisone and abiraterone compared to baseline, ipatasertib monotherapy and ipatasertib-prednisone/prednisolone combination. Increased ipatasertib exposures in combination with abiraterone and prednisone/prednisolone were correlated with increased glucose levels.
  Timing of food and dose can modulate the glucose changes observed post ipatasertib administration. Reduced peak glucose levels and improved % time in ranges were observed when ipatasertib was administered in the evening (2 hours post-meal) in combination with prednisone/prednisolone and abiraterone compared to when ipatasertib-prednisone/prednisolone-abiraterone combination was administered in the morning (meal 1 hour post-dose administration).
  There was no impact of COVID-19 on the study results and conclusions.

• REC name

  London - Chelsea Research Ethics Committee

• REC reference

  12/LO/0565

• Date of REC Opinion

  20 Apr 2012

• REC opinion

  Favourable Opinion