Clinical Trials List
Protocol NumberCO39303
NCT Number(ClinicalTrials.gov Identfier)NCT03072238
Completed
2017-06-15 - 2025-12-31
Phase III
Terminated4
ICD-10C61
Malignant neoplasm of prostate
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
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Trial Applicant
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Sponsor
ROCHE PRODUCTS LTD.
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Trial scale
Multi-Regional Multi-Center
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Update
2026/09/15
Investigators and Locations
Co-Principal Investigator
- 裘坤元 Division of Urology
- Chuan-Shu Chen Division of Urology
- Cheng-Kuang Yang Division of Urology
- Chia-Yen Lin Division of Urology
- 蔡世傳 Division of Urology
- 熊小澐 Division of Urology
- Jian-Ri Li Division of Urology
- Cheng-Che Chen Division of Urology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Chao-Hsiang Chang Division of Urology
- Yi-Huei Chang Division of Urology
- Chi-Ping Huang Division of Urology
- 陳冠亨 Division of Urology
- Su-Peng Yeh Division of Hematology & Oncology
- Che-Hung Lin Division of Hematology & Oncology
- Ching-Chan Lin Division of Hematology & Oncology
- Chi-Rei Yang Division of Urology
- Po-Jen Hsiao Division of Urology
- Po-Fan Hsieh Division of Urology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 黃俊農 Division of Urology
- Yung-Chin Lee Division of Urology
- Tsung-Yi Huang Division of Urology
- Hsiang Ying Lee Division of Urology
- 耿俊閎 Division of Urology
- 李政學 Division of Urology
- HSIN-LING YIN Division of Others -
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
Audit
None
Co-Principal Investigator
Audit
None
Principal Investigator
Yung-Chang Lin
Linkou Chang Gung Medical Foundation
Taiwan National PI
林永昌
Co-Principal Investigator
- Feng-Yuan Liu Division of Nuclear Medicine
- Rita cheng Division of Hematology & Oncology
- Po-Jung Su Division of Hematology & Oncology
- 劉忠一 Division of Urology
- See-Tong Pang Division of Hematology & Oncology
- 黃成之 Division of Radiology
- 張英勛 Division of Hematology & Oncology
- Kai-Jie Yu Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
9 Terminated
Audit
None
Condition/Disease
Metastatic Prostate Cancer
Objectives
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).
Test Drug
Ipatasertib
Active Ingredient
Ipatasertib
Dosage Form
tablet
Dosage
200mg
100mg
100mg
Endpoints
Investigator-assessed Radiographic Progression-free Survival (rPFS), Per Prostate Cancer Working Group 3 (PCWG3) Criteria in Phosphatase and Tensin Homolog (PTEN) Loss Population rPFS was defined as time from date of randomization to the first occurrence of documented disease progression (PD), as assessed by the investigator with use of the PCWG3 criteria or death from any cause, whichever occurs first. PD for soft tissue was defined as at least a 20% increase in the sum of diameters (SOD) of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 millimeters (mm) in the SOD of target lesions; progression of non-target lesions; the appearance of one or more new lesions according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) criteria. PD for bone lesions was defined as 2 or more new lesions compared to baseline followed by a confirmatory bone scan at least 6 weeks later according to the PCWG3 criteria. The Kaplan-Meier (KM) estimate was used to determine the median rPFS. Up to approximately 32 months
Investigator-assessed rPFS, Per PCWG3 Criteria in ITT Population rPFS was defined as time from date of randomization to the first occurrence of documented PD, as assessed by the investigator with use of the PCWG3 criteria or death from any cause, whichever occurs first. PD for soft tissue was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm in the SOD of target lesions; progression of non-target lesions; the appearance of one or more new lesions according to RECIST v1.1 criteria. PD for bone lesions was defined as 2 or more new lesions compared to baseline followed by a confirmatory bone scan at least 6 weeks later according to the PCWG3 criteria. The KM estimate was used to determine the median rPFS. Up to approximately 32 months
Investigator-assessed rPFS, Per PCWG3 Criteria in ITT Population rPFS was defined as time from date of randomization to the first occurrence of documented PD, as assessed by the investigator with use of the PCWG3 criteria or death from any cause, whichever occurs first. PD for soft tissue was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm in the SOD of target lesions; progression of non-target lesions; the appearance of one or more new lesions according to RECIST v1.1 criteria. PD for bone lesions was defined as 2 or more new lesions compared to baseline followed by a confirmatory bone scan at least 6 weeks later according to the PCWG3 criteria. The KM estimate was used to determine the median rPFS. Up to approximately 32 months
Inclution 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
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
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 Exclusion Criteria:
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
Abiraterone-Specific Exclusion Criteria:
Uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 95 mmHg)
History of pituitary or adrenal dysfunction
Any ongoing cardiac arrhythmias (including atrial fibrillation) that require medical 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)
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 Exclusion Criteria:
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
Abiraterone-Specific Exclusion Criteria:
Uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 95 mmHg)
History of pituitary or adrenal dysfunction
Any ongoing cardiac arrhythmias (including atrial fibrillation) that require medical 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)
The Estimated Number of Participants
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Taiwan
23 participants
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Global
1100 participants
