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
Description
Brief Summary
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).
Phase
N/AInclusion and Exclusion 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 to use the electronic device to report selected study outcomes; Caregivers and site staff can assist with patient diary input but patient must be able to independently comprehend and answer the questionnaires
- 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. If only 12-14 slides are available, the patient may still be eligible for the study, after discussion with and approval by the Medical Monitor. Cytologic or fine-needle aspiration samples are not acceptable. Tumor tissue from bone metastases is not acceptable
- A valid PTEN IHC result (testingcentral laboratory tested with results directly sent to IxRS) (e.g., participants with an "invalid" or "failed" PTEN IHC result are not permitted to enroll)
- Metastatic disease documented prior to randomization by clear evidence of bone lesions on bone scan and/or measurable soft tissue disease by computed tomography (CT) and/or magnetic resonance imaging (MRI) (at least one target lesion) according to RECIST v1.1
- 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 (<= 1.7 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 of more than 10 mg/day of prednisone or an equivalent dose of other anti-inflammatory corticosteroids as a current systemic corticosteroid therapy to treat a chronic disease (e.g., rheumatic disorder)
- 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), untreated 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; previously documented LVEF < 50% without documentation of recovery), clinically significant electrolyte abnormalities (e.g., hypokalemia, hypomagnesemia, hypocalcemia), or family history of sudden unexplained death or long QT syndrome
- History of another malignancy within 5 years prior to randomization, except for either adequately treated non-melanomatous carcinoma of the skin, adequately treated melanoma in situ, adequately treated non-muscle-invasive urothelial carcinoma of the bladder (Tis, Ta, and low grade T1 tumors), or other malignancies where the patient has undergone potentially curative therapy with no evidence of disease and are deemed by the treating physician to have a recurrence rate of <5% at 5 years
- 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
- Pathologic findings consistent with small-cell or neuroendocrine carcinoma of the prostate
- Any therapy including chemotherapy (e.g., docetaxel) or biological therapy (e.g., vaccine, immunotherapy) for the treatment of castration-resistant prostate cancer. Previous treatment with flutamide, steroidal anti-androgens, androgens, estrogens, bicalutamide, nilutamide, or 5-
Sites
Please contact the trial administrator to learn more about where you can participate in this trial. Please use the contact form on the right side.
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