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

Genentech

Status and phase: Completed; Phase 2; Phase 1

Conditions: Prostate Cancer

Treatments: Drug: Ipatasertib; Drug: Apitolisib; Drug: Placebo; Drug: Abiraterone; Drug: Prednisolone; Drug: Prednisone

Study type: Interventional

Funder types: Industry

Identifiers

NCT01485861

2011-004126-10 (EudraCT Number)

GO27983

Details and patient eligibility

About

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in combination with abiraterone and of apitolisib administrated in combination with abiraterone (this phase is no longer active), a Phase II, 3-arm, double-blind, randomized comparison of ipatasertib with abiraterone and prednisone/prednisolone versus placebo with abiraterone and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.

Enrollment: 298 patients

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

---

298 participants in 6 patient groups, including a placebo group

Phase Ib: Ipatasertib 400 mg + abiraterone

Experimental group

Description:

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.

Treatment:

Drug: Prednisone

Drug: Abiraterone

Drug: Prednisolone

Drug: Ipatasertib

Phase Ib: Apitolisib 30 mg + abiraterone

Experimental group

Description:

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.

Treatment:

Drug: Prednisone

Drug: Abiraterone

Drug: Apitolisib

Drug: Prednisolone

Phase II: Ipatasertib 400 mg + abiraterone

Experimental group

Description:

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.

Treatment:

Drug: Prednisone

Drug: Abiraterone

Drug: Prednisolone

Drug: Ipatasertib

Phase II: Ipatasertib 200 mg + abiraterone

Experimental group

Description:

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.

Treatment:

Drug: Prednisone

Drug: Abiraterone

Drug: Prednisolone

Drug: Ipatasertib

Phase II: Placebo + abiraterone

Placebo Comparator group

Description:

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.

Treatment:

Drug: Prednisone

Drug: Abiraterone

Drug: Prednisolone

Drug: Placebo

Safety Cohort: Ipataseritib 400 mg + Abiraterone + Prednisone

Experimental group

Description:

Participants will receive ipatasertib 400 mg orally once daily and/or prednisone/prednisolone 5 mg orally once daily or bid and/or abiraterone 1000 mg orally once daily according to the following schedule: ipatasertib in the morning during Cycle 1, Days 1-7; ipatasertib in the morning plus prednisone/prednisolone once at night during Cycle 1, Day 8; ipatasertib in the morning plus prednisone/prednisolone bid (morning and night) during Cycle 1, Days 9-11; ipatasertib in the morning plus prednisone/prednisolone bid (morning and night) and abiraterone in the morning during Cycle 1, Days 12-18; ipatasertib in the evening plus prednisone/prednisolone bid (morning and night) and abiraterone at the same time as ipatasertib during Cycle 1, Days 19-25; Cycle 2 and beyond ipatasertib once daily in the morning or evening, abiraterone at the same time as ipatasertib, and prednisone/prednisolone bid.

Treatment:

Drug: Prednisone

Drug: Abiraterone

Drug: Prednisolone

Drug: Ipatasertib