Ipatasertib Plus Abiraterone Plus Prednisone/Prednisolone, Relative to Placebo Plus Abiraterone Plus Prednisone/Prednisolone in Adult Male Patients With Metastatic Castrate-Resistant Prostate Cancer

Study ID
STU 032017-085

Study Sites

  • Clements University Hospital

Contact
Allison Beaver
214/645-8788
ALLISON.BEAVER@UTSouthwestern.edu

Principal Investigator
Kevin Courtney, M.D., Ph.D.

Official Title

A Phase III, Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial Testing Ipatasertib Plus Abiraterone Plus Prednisone/Prednisolone, Relative to Placebo Plus Abiraterone Plus Prednisone/Prednisolone in Adult Male Patients With Asymptomatic or Mildly Symptomatic, Previously Untreated, Metastatic Castrate-Resistant Prostate Cancer

Brief Overview

The purpose of this study is to evaluate the efficacy, safety, and pharmacokinetics of ipatasertib plus abiraterone and prednisone/prednisolone compared with placebo plus abiraterone and prednisone/prednisolone in participants with metastatic castrate-resistant prostate cancer (mCRPC).

Eligibility

Inclusion Criteria:
- Eastern Collaborative Oncology Group (ECOG) performance status of 0 or 1 at screening
- Adequate hematologic and organ function within 28 days before the first study treatment
- Ability to comply with the study protocol, in the investigator's judgment
- Willingness and ability of participants (or observers, caregivers) to use the electronic device to report selected study outcomes
- Life expectancy of at least 6 months
- Agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm
- For enrollment into the China extension cohort, residence in the People's Republic of China
Disease-specific Inclusion Criteria:
- Histologically confirmed prostate adenocarcinoma without neuroendocrine differentiation or small-cell features
- Consent to provide a formalin-fixed paraffin-embedded (FFPE) tissue block (preferred) or a minimum of 15 (20 preferred) freshly cut unstained tumor slides from the most recently collected, available tumor tissue accompanied by an associated pathology report (with tumor content information, Gleason score, and disease staging) for PTEN IHC and NGS testing and for other protocol-mandated secondary and exploratory assessments. Cytologic or fine-needle aspiration samples are not acceptable. Tumor tissue from bone metastases that is subject to decalcification is not acceptable.
- A valid PTEN IHC result (per central testing) (e.g., participants with an "invalid" or "failed" PTEN IHC result are not permitted to enroll)
- Metastatic disease documented prior to randomization by bone lesions on bone scan or soft tissue disease by computed tomography (CT) or magnetic resonance imaging (MRI)
- Asymptomatic or mildly symptomatic form of prostate cancer
- Progressive disease before initiating study treatment
- Ongoing androgen deprivation with gonadotropin-releasing hormone (GnRH) analog or bilateral orchiectomy, with serum testosterone < 50 ng/dL (< 2.0 nmol/L) within 28 days before randomization
Exclusion Criteria:
- Inability or unwillingness to swallow whole pills
- History of malabsorption syndrome or other condition that would interfere with enteral absorption
- Clinically significant history of liver disease consistent with Child-Pugh Class B or C, including cirrhosis, current alcohol abuse, or current known active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV)
- Need for current chronic corticosteroid therapy (> 10 mg/day of prednisone or an equivalent dose of other anti-inflammatory corticosteroids)
- Active infection requiring intravenous (IV) antibiotics within 14 days before Day 1, Cycle 1
- Immunocompromised status because of current known active infection with HIV or because of the use of immunosuppressive therapies for other conditions
- Major surgical procedure or significant traumatic injury within 28 days prior to Day 1, Cycle 1, or anticipation of the need for major surgery during study treatment
- History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias, such as structural heart disease (e.g., severe left ventricular systolic dysfunction, left ventricular hypertrophy), coronary heart disease (symptomatic or with ischemia demonstrated by diagnostic testing), myocardial infarction or atrial thrombotic events within the past 6 months, severe unstable angina, New York Heart Association Class III and IV heart disease or depressed left ventricular ejection fraction (LVEF; < 50%), clinically significant electrolyte abnormalities (e.g., hypokalemia, hypomagnesemia, hypocalcemia), or family history of sudden unexplained death or long QT syndrome
- Current treatment with medications that are well known to prolong the QT interval
- History of other malignancy within the previous 5 years, except for appropriately treated non-melanoma skin carcinoma, or participants who have undergone potentially curative therapy with no evidence of disease and are deemed by the treating physician to be at low risk for recurrence
- Any other diseases, cardiovascular, pulmonary, or metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or renders the participants at high risk from treatment complications.
Disease-Specific Exclusion Criteria:
- Pathologic findings consistent with small-cell or neuroendocrine carcinoma of the prostate
- Treatment with chemotherapy for the treatment of castration-resistant prostate cancer
- Use of opiate analgesics for cancer-related pain, including codeine and dextropropoxyphene, currently or any time within 4 weeks of Day 1, Cycle 1
- Any prior anti-cancer therapy
- Known untreated or active central nervous system (CNS) metastases (progressing or requiring anticonvulsant medications or corticosteroids for symptomatic control); a CT or MRI scan of the brain will be performed at screening if required by the local health authority
- Any chronic therapy or use of food supplements that are strong CYP3A4/5 inducers or sensitive CYP2D6 substrates with a narrow therapeutic window
Abiraterone-Specific Exclusion Criteria:
- Uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 95 mmHg)
- History of pituitary or adrenal dysfunction
- Atrial fibrillation or other cardiac arrhythmia requiring therapy
Ipatasertib-Specific Exclusion Criteria:
- Type 1 or Type 2 diabetes mellitus requiring insulin at study entry
- History of inflammatory bowel disease (e.g., Crohn disease and ulcerative colitis), active bowel inflammation (e.g., diverticulitis)