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Study of Ipatasertib or Apitolisib With Abiraterone Acetate Versus Abiraterone Acetate in Participants With Castration-Resistant Prostate Cancer Previously Treated With Docetaxel Chemotherapy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01485861
Recruitment Status : Recruiting
First Posted : December 6, 2011
Last Update Posted : June 17, 2020
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.

Brief Summary:
This multicenter, international, Phase Ib/II trial consists of three stages: a Phase Ib, open-label stage in which the recommended Phase II dose was determined for ipataseritib administrated in combination with abiraterone and of GDC-0980 administrated in combination with abiraterone (this phase is no longer active), a Phase II, 3-arm, double-blind, randomized comparison of ipatasertib with abiraterone and prednisone/prednisolone versus placebo with abiraterone and prednisone/prednisolone and a safety single-arm, open-label cohort of ipatasertib 400 mg daily alone or in combination with prednisone/prednisolone or prednisone/prednisolone plus abiraterone.

Condition or disease Intervention/treatment Phase
Prostate Cancer Drug: Abiraterone Drug: Apitolisib Drug: Ipatasertib Drug: Placebo Drug: Prednisone Drug: Prednisolone Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 295 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase Ib/II Study of Ipatasertib (GDC-0068) or Apitolisib (GDC-0980) With Abiraterone Acetate Versus Abiraterone Acetate in Patients With Castration-Resistant Prostate Cancer Previously Treated With Docetaxel-Based Chemotherapy
Actual Study Start Date : January 11, 2012
Estimated Primary Completion Date : March 30, 2021
Estimated Study Completion Date : April 30, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
Experimental: Phase Ib: Ipatasertib 400 mg + abiraterone
Participants will receive ipatasertib 400 mg once daily, abiraterone 1000 mg once daily, and prednisone/prednisolone 5 mg twice daily (bid) continuously in 28-day treatment cycles until disease progression or intolerable toxicity.
Drug: Abiraterone
Orally once daily

Drug: Ipatasertib
Orally once daily

Drug: Prednisone
Orally bid

Drug: Prednisolone
Orally bid

Experimental: Phase Ib: Apitolisib 30 mg + abiraterone
Participants will receive apitolisib 30 mg once daily, abiraterone 1000 mg once daily, and prednisone/prednisolone 5 mg twice daily (bid) continuously in 28-day treatment cycles until disease progression or intolerable toxicity.
Drug: Abiraterone
Orally once daily

Drug: Apitolisib
Orally once daily

Drug: Prednisone
Orally bid

Drug: Prednisolone
Orally bid

Experimental: Phase II: Ipatasertib 400 mg + abiraterone
Participants will receive Ipatasertib 400 mg once daily, abiraterone 1000 mg once daily, and prednisone/prednisolone 5 mg bid continuously in 28-day treatment cycles until disease progression or intolerable toxicity.
Drug: Abiraterone
Orally once daily

Drug: Ipatasertib
Orally once daily

Drug: Prednisone
Orally bid

Drug: Prednisolone
Orally bid

Experimental: Phase II: Ipatasertib 200 mg + abiraterone
Participants will receive Ipatasertib 200 mg once daily, abiraterone 1000 mg once daily, and prednisone/prednisolone 5 mg bid continuously in 28-day treatment cycles until disease progression or intolerable toxicity.
Drug: Abiraterone
Orally once daily

Drug: Ipatasertib
Orally once daily

Drug: Prednisone
Orally bid

Drug: Prednisolone
Orally bid

Placebo Comparator: Phase II: Placebo + abiraterone
Participants will receive placebo (for Ipatasertib) once daily, abiraterone 1000 mg once daily, and prednisone/prednisolone 5 mg bid continuously in 28-day treatment cycles until disease progression or intolerable toxicity.
Drug: Abiraterone
Orally once daily

Drug: Placebo
Orally once daily

Drug: Prednisone
Orally bid

Drug: Prednisolone
Orally bid

Experimental: Safety Cohort: Ipataseritib 400 mg + Abiraterone + Prednisone

Participants will receive Ipataseritib 400 mg once daily in the AM for Cycle 1 day 1-18. On Day 19, Ipataseritib 400 mg will be switched to PM dosing for the remainder of the Cycle 1.

Prednisone 5 mg starts in the PM of Cycle 1 day 8 and taken BID thereafter for the remainder of the study treatment Abiraterone 1000mg once a day starts on Cycle1 day 12 in the AM and should be taken at the same time as Ipataseritib. Starting from cycle 1 day 19, Ipataseritib and Abiraterone are dosed in PM at should be taken together at the same time each day until cycle 2 day 1. Starting from Cycle 2 Day 1, Participants may choose to take Ipatasertib and Abiraterone in either the AM or PM; however, they should be taken together at approximately the same time each day.

Participants will receive the study treatment until disease progression or intolerable toxicity.

Drug: Abiraterone
Orally once daily

Drug: Ipatasertib
Orally once daily

Drug: Prednisone
Orally bid

Drug: Prednisolone
Orally bid




Primary Outcome Measures :
  1. Phase Ib: Percentage of Participants With Dose Limiting Toxicity (DLTs) [ Time Frame: Days 1 to 28 of Cycle 1 (Cycle length = 28 days) ]
  2. Phase Ib: Percentage of Participants by Nature of DLTs [ Time Frame: Days 1 to 28 of Cycle 1 (Cycle length = 28 days) ]
  3. Phase Ib: Recommended Phase II Dose (RP2D) of Ipatasertib [ Time Frame: Days 1 to 28 of Cycle 1 (Cycle length = 28 days) ]
  4. Phase II: Percentage of Participants With Radiographic Progression (as Assessed by Response Evaluation Criteria in Solid Tumors [RECIST] 1.1) or Death - Intent to Treat (ITT) Population [ Time Frame: Screening up to radiographic progression or death, whichever occurs first (assessed at screening, after Cycles 3, 5, 7, 9, every three cycles [12 weeks] thereafter, and at treatment completion [up to 3.6 years overall]) (cycle length = 28 days) ]
  5. Phase II: Radiographic Progression Free Survival as Assessed by RECIST 1.1 - ITT Population [ Time Frame: Screening up to radiographic progression or death, whichever occurs first (assessed at screening, after Cycles 3, 5, 7, 9, every three cycles [12 weeks] thereafter, and at treatment completion [up to 3.6 years overall]) (cycle length = 28 days) ]
  6. Phase II: Percentage of Participants With Radiographic Progression (as Assessed by RECIST 1.1) or Death in Participants With Institute of Cancer Research (ICR) Phosphatase and Tensin Homolog (PTEN) Loss [ Time Frame: Screening up to radiographic progression or death, whichever occurs first (assessed at screening, after Cycles 3, 5, 7, 9, every three cycles [12 weeks] thereafter, and at treatment completion [up to 3.6 years overall]) (cycle length = 28 days) ]
  7. Phase II: Radiographic Progression Free Survival (as Assessed by RECIST 1.1) in Participants With ICR PTEN Loss [ Time Frame: Screening up to radiographic progression or death, whichever occurs first (assessed at screening, after Cycles 3, 5, 7, 9, every three cycles [12 weeks] thereafter, and at treatment completion [up to 3.6 years overall]) (cycle length = 28 days) ]
  8. Phase Ib: Percentage of Participants with AEs, graded according to the NCI CTCAE v4.0 [ Time Frame: Baseline to Treatment Completion (Up to 3.6 years) ]

Secondary Outcome Measures :
  1. Phase II: Percentage of Participants Who Died - ITT Population [ Time Frame: Screening up to death (assessed at screening, after Cycles 3, 5, 7, 9, every three cycles [12 weeks] thereafter up to end of treatment [up to 3.6 years overall]) (cycle length = 28 days) ]
  2. Phase II: Overall Survival - ITT Population [ Time Frame: Screening up to death (assessed at screening, after Cycles 3, 5, 7, 9, every three cycles [12 weeks] thereafter up to end of treatment [up to 3.6 years overall]) (cycle length = 28 days) ]
  3. Phase II: Percentage of Participants Who Died in Participants With ICR PTEN Loss [ Time Frame: Screening up to death (assessed at screening, after Cycles 3, 5, 7, 9, every three cycles [12 weeks] thereafter up to end of treatment [up to 3.6 years overall]) (cycle length = 28 days) ]
  4. Phase II: Overall Survival in Participants With ICR PTEN Loss [ Time Frame: Screening up to death (assessed at screening, after Cycles 3, 5, 7, 9, every three cycles [12 weeks] thereafter up to end of treatment [up to 3.6 years overall]) (cycle length = 28 days) ]
  5. Phase II: Percentage of Participants With Prostate-Specific Antigen (PSA) Progression (as Assessed by Prostate Cancer Working Group 2 Criteria) - ITT Population [ Time Frame: Screening up to PSA progression (assessed at screening, after Cycles 3, 5, 7, 9, every three cycles [12 weeks] thereafter up to end of treatment [up to 3.6 years overall]) (cycle length = 28 days) ]
  6. Phase II: Time to PSA Progression (as Assessed by Prostate Cancer Working Group 2 Criteria) - ITT Population [ Time Frame: Screening up to PSA progression (assessed at screening, after Cycles 3, 5, 7, 9, every three cycles [12 weeks] thereafter up to end of treatment [up to 3.6 years overall]) (cycle length = 28 days) ]
  7. Phase II: Percentage of Participants With PSA Progression (as Assessed by Prostate Cancer Working Group 2 Criteria) in Participants With ICR PTEN Loss [ Time Frame: Screening up to PSA progression (assessed at screening, after Cycles 3, 5, 7, 9, every three cycles [12 weeks] thereafter up to end of treatment [up to 3.6 years overall]) (cycle length = 28 days) ]
  8. Phase II: Time to PSA Progression (as Assessed by Prostate Cancer Working Group 2 Criteria) in Participants With ICR PTEN Loss [ Time Frame: Screening up to PSA progression (assessed at screening, after Cycles 3, 5, 7, 9, every three cycles [12 weeks] thereafter up to end of treatment [up to 3.6 years overall]) (cycle length = 28 days) ]
  9. Phase II: Percentage of Participants With PSA Response - ITT Population [ Time Frame: Baseline, Day 1 of every cycle (starting from Cycle 2) till 30 days after last dose (up to overall 3.6 years) (cycle length = 28 days) ]
  10. Phase II: Percentage of Participants With PSA Response in Participants With ICR PTEN Loss [ Time Frame: Baseline, Day 1 of every cycle (starting from Cycle 2) till 30 days after last dose (up to overall 3.6 years) (cycle length = 28 days) ]
  11. Phase II: Percentage of Participants With Objective Response as Assessed by RECIST 1.1 - ITT Population [ Time Frame: Screening up to radiographic progression or death, whichever occurred first (assessed at screening, after Cycles 3, 5, 7, 9, every three cycles [12 weeks] thereafter up to end of treatment [up to 3.6 years overall]) (cycle length = 28 days) ]
  12. Phase II: Percentage of Participants With Objective Response (as Assessed by RECIST 1.1) in Participants With ICR PTEN Loss [ Time Frame: Screening up to radiographic progression or death, whichever occurred first (assessed at screening, after Cycles 3, 5, 7, 9, every three cycles [12 weeks] thereafter up to end of treatment [up to 3.6 years overall]) (cycle length = 28 days) ]
  13. Phase II: Duration of Tumor Response, as Assessed by RECIST 1.1 - ITT Population [ Time Frame: Screening up to radiographic progression or death, whichever occurred first (assessed at screening, after Cycles 3, 5, 7, 9, every three cycles [12 weeks] thereafter up to end of treatment [up to 3.6 years overall]) (cycle length = 28 days) ]
  14. Phase II: Percentage of Participants With Circulating Tumor Cells (CTC) Reduction Response - ITT Population [ Time Frame: Screening, on Day 1 of Cycle 2, on Day 1 of Cycle 3, and at the treatment completion visit (up to overall 3.6 years) (cycle length=28 days) ]
  15. Phase II: Percentage of Participants With CTC Reduction Response in Participants With ICR PTEN Loss [ Time Frame: Baseline, on Day 1 of Cycle 2, on Day 1 of Cycle 3, and at the treatment completion visit (up to overall 3.6 years) (cycle length=28 days) ]
  16. Phase II: Percentage of Participants With CTC Conversion - ITT Population [ Time Frame: Baseline, on Day 1 of Cycle 2, on Day 1 of Cycle 3, and at the treatment completion visit (up to overall 3.6 years) (cycle length=28 days) ]
  17. Phase II: Percentage of Participants With CTC Conversion in Participants With ICR PTEN Loss [ Time Frame: Baseline, on Day 1 of Cycle 2, on Day 1 of Cycle 3, and at the treatment completion visit (up to overall 3.6 years) (cycle length=28 days) ]
  18. Phase II: Percentage of Participants With Pain Progression - ITT Population [ Time Frame: Screening, Day 1 of each cycle (cycle length=28 days) up to treatment completion (up to 3.6 years) ]
  19. Phase II: Time to Pain Progression - ITT Population [ Time Frame: Screening, Day 1 of each cycle (cycle length=28 days) up to treatment completion (up to 3.6 years) ]
  20. Phase II: Percentage of Participants With Pain Progression in Participants With ICR PTEN Loss [ Time Frame: Screening, Day 1 of each cycle (cycle length=28 days) up to treatment completion (up to 3.6 years) ]
  21. Phase II: Time to Pain Progression in Participants With ICR PTEN Loss [ Time Frame: Screening, Day 1 of each cycle (cycle length=28 days) up to treatment completion (up to 3.6 years) ]
  22. Phase Ib: Maximum Plasma Concentration (Cmax) (in nanograms per milliliter [ng/mL]) of Ipatasertib and Apitolisib When Co-Administered With Abiraterone [ Time Frame: Predose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length=28 days) ]
  23. Phase Ib: Time to Cmax (tmax) (in hours) of Ipatasertib and Apitolisib When Co-Administered With Abiraterone [ Time Frame: Predose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length=28 days) ]
  24. Phase Ib: Area Under The Concentration Time Curve From Time 0 to 24 Hours (AUC0-24) (in ng/mL*hours) of Ipatasertib and Apitolisib When Co-Administered With Abiraterone [ Time Frame: Predose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length=28 days) ]
  25. Phase Ib: Total Body Clearance (CL/F) of Ipatasertib When Co-Administered With Abiraterone [ Time Frame: Predose (0 hour), 1, 2, 4, 6, 24 hours post dose on Day 15 of Cycle 1 (cycle length=28 days) ]
  26. Phase Ib: Accumulation Ratio of Ipatasertib When Co-Administered With Abiraterone [ Time Frame: Predose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length=28 days) ]
  27. Cmax of G-037720 (Metabolite of Ipatasertib) [ Time Frame: Predose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length=28 days) ]
  28. tmax of G-037720 (Metabolite of Ipatasertib) [ Time Frame: Predose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length=28 days) ]
  29. Phase Ib: AUC0-24 of G-037720 (Metabolite of Ipatasertib) [ Time Frame: Predose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length=28 days) ]
  30. Phase Ib: Accumulation Ratio of G-037720 (Metabolite of Ipatasertib) [ Time Frame: Predose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length=28 days) ]
  31. Phase Ib: Cmax of Abiraterone When Co-Administered With Ipatasertib or Apitolisib [ Time Frame: Predose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length=28 days) ]
  32. Phase Ib: tmax of Abiraterone When Co-Administered With Ipatasertib or Apitolisib [ Time Frame: Predose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length=28 days) ]
  33. Phase Ib: AUC0-24 of Abiraterone When Co-Administered With Ipatasertib or Apitolisib [ Time Frame: Predose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length=28 days) ]
  34. Phase Ib: Plasma Half-Life of Abiraterone When Co-Administered With Ipatasertib or Apitolisib [ Time Frame: Predose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length=28 days) ]
  35. Phase Ib: Accumulation Ratio of Abiraterone When Co-Administered With Ipatasertib or Apitolisib [ Time Frame: Predose (0 hour), 1, 2, 4, 6, 24 hours post dose on Days 1, 15 of Cycle 1 (cycle length=28 days) ]
  36. Safety Cohort: Percentage of Participants with AEs, Graded According to the NCI CTCAE v4.0 [ Time Frame: Day -1 of Cycle 1 to Day 1 of Cycle 2 (cycle length=25 days) ]
  37. Safety Cohort: Comparing of Average and Peak Glucose over 24h by CGM for Participants Receiving Ipataseritib+Prednisone+Abiraterone with AM Dosing of Ipatasertib [ Time Frame: Day -1 of Cycle 1 to Day 1 of Cycle 2 (cycle lenght=25 days) ]
  38. Safety Cohort: Comparing of Average and Peak Glucose over 24h by CGM for Participants Receiving Ipataseritib+Prednisone+Abiraterone with PM Dosing of Ipatasertib [ Time Frame: Day -1 of Cycle 1 to Day 1 of Cycle 2 (cycle lenght=25 days) ]
  39. Safety Cohort: Comparing of Average and Peak Glucose Over 24h by CGM for Participants Receiving Ipatasertib Alone [ Time Frame: Day -1 of Cycle 1 to Day 1 of Cycle 2 (cycle lenght=25 days) ]
  40. Safety Cohort: Comparing of Average and Peak Glucose Over 24h by CGM for Participants Receiving Ipatasertib+Prednisone [ Time Frame: Day -1 of Cycle 1 to Day 1 of Cycle 2 (cycle lenght=25 days) ]
  41. Safety Cohort: Comparing of Average and Peak Glucose Over 24h by CGM for Participants Receiving Ipatasertib+Prednisone+Abiraterone [ Time Frame: Day -1 of Cycle 1 to Day 1 of Cycle 2 (cycle lenght=25 days) ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed metastatic or advanced prostate adenocarcinoma that has been previously treated with docetaxel-based therapy and has progressed during treatment of at least one hormonal therapy(prior docetaxel is not required for the safety cohort)
  • Two rising PSA levels greater than or equal to (>/=) 2 ng/mL measured >/= 1 week apart or radiographic evidence of disease progression in soft tissue or bone
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at screening
  • Adequate hematologic and organ function
  • Documented willingness to use an effective means of contraception
  • Safety cohort only: agreement to use CGM for first cycle of treatment

Exclusion Criteria:

  • History of Type I or Type II diabetes mellitus requiring insulin; safety cohort: patients who are receiving any pharmacologic treatment for diabetes are not eligible
  • New York Heart Association Class III or IV heart failure or Left ventricular ejection fraction < 50% or ventricular arrhythmia requiring medication
  • Significant atherosclerotic disease, as evidenced by: unstable angina, history of myocardial infarction within 6 months prior to Day 1, or cerebrovascular accident within 6 months prior to Day 1
  • Active autoimmune disease that is not controlled by nonsteroidal anti-inflammatory drugs or active inflammatory disease which requires immunosuppressive therapy
  • Clinically significant history of liver disease
  • History of adrenal insufficiency or hyperaldosteronism
  • Phase II only: Previous therapy for prostate cancer with 17 alpha-hydroxylase/C17,20-lyase inhibitors, including abiraterone
  • Phase II only: Previous treatment for prostate cancer with Protein kinase B phosphatidylinositol 3 kinase and/or mammalian target of rapamycin inhibitors
  • Need for chronic corticosteroid therapy of >/= 20 mg of prednisone per day or an equivalent dose of other anti inflammatory corticosteroids or immunosuppressant

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01485861


Contacts
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Contact: Reference Study ID Number: GO27983 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global-roche-genentech-trials@gene.com

Locations
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Sponsors and Collaborators
Genentech, Inc.
Investigators
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Study Director: Clinical Trials Genentech, Inc.
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Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT01485861    
Other Study ID Numbers: GO27983
2011-004126-10 ( EudraCT Number )
First Posted: December 6, 2011    Key Record Dates
Last Update Posted: June 17, 2020
Last Verified: June 2020
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Prednisone
Prednisolone
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents