Ipatasertib Plus Abiraterone Plus Prednisone/Prednisolone, Relative to Placebo Plus Abiraterone Plus Prednisone/Prednisolone in Adult Male Patients With Metastatic Castrate-Resistant Prostate Cancer
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Keep this study
Lead
Hoffmann-La Roche
Age
18–any
Sex
MALE
Healthy volunteers
Not accepted
You may be eligible if
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
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
You may not be if
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.
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-α reductase inhibitor is permitted.
Use of opioid medications for cancer-related pain, including codeine and dextropropoxyphene, currently or any time within 4 weeks of Day 1, Cycle 1
Prior treatment with abiraterone or other known potent CYP17 inhibitors (e.g., ketoconazole, orteronel) or investigational agents that block androgen synthesis. Previous treatment with itraconazole and fluconazole is permitted.
Prior treatment with enzalutamide or other potent androgen-receptor blockers, approved or experimental (e.g., ARN-509, ODM-201, or galeterone)
Prior treatment with flutamide (Eulexin®), steroidal anti-androgens (e.g., cyproterone acetate, chlormadinone acetate), androgens, or estrogens treatment within 4 weeks of Cycle 1, Day 1
Prior treatment with bicalutamide (Casodex®) or nilutamide (Nilandron®) within 6 weeks of Cycle 1, Day 1
Prior treatment with 5-alpha reductase inhibitors within 4 weeks of Cycle 1, Day 1
Prior treatment with systemic radiopharmaceuticals (e.g., radium-223 and strontium-89). Radiopharmaceuticals for the purpose of imaging are permitted. Focal palliative radiation to treat cancer-related pain is permitted provided that the last treatment with radiation is at least 14 days prior to Cycle 1, Day 1.
Prior treatment with approved or experimental therapeutic agents with known inhibition of the PI3K pathway, including PI3K inhibitors, AKT inhibitors, and mTOR inhibitors
Administration of an investigational therapeutic agent within 28 days of Cycle 1, Day 1
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 inhibitors or sensitive substrates of CYP3A or CYP2D6 with a narrow therapeutic window
Any ongoing cardiac arrhythmias (including atrial fibrillation) that require medical therapy
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)
Clareo Health | Ipatasertib Plus Abiraterone Plus Prednisone/Prednisolone, Relative to Placebo Plus Abiraterone Plus Prednisone/Prednisolone in Adult Male Patients With Metastatic Castrate-Resistant Prostate Cancer
