NCT03072238已完成3 期
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
适应症
干预措施
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,101
- 试验地点
- 176
- 主要终点
- Investigator-assessed Radiographic Progression-free Survival (rPFS), Per Prostate Cancer Working Group 3 (PCWG3) Criteria in Phosphatase and Tensin Homolog (PTEN) Loss Population
研究概览
简要总结
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
- •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)
研究组 & 干预措施
Placebo + Abiraterone
Active Comparator
Participants received Placebo plus Abiraterone (along with Prednisone/Prednisolone), administered orally in 28-day cycles.
干预措施: Abiraterone (Drug)
Placebo + Abiraterone
Active Comparator
Participants received Placebo plus Abiraterone (along with Prednisone/Prednisolone), administered orally in 28-day cycles.
干预措施: Placebo (Drug)
Placebo + Abiraterone
Active Comparator
Participants received Placebo plus Abiraterone (along with Prednisone/Prednisolone), administered orally in 28-day cycles.
干预措施: Prednisone/Prednisolone (Drug)
Ipatasertib + Abiraterone
Experimental
Participants received Ipatasertib plus Abiraterone (along with Prednisone/Prednisolone), administered orally in 28-day cycles.
干预措施: Ipatasertib (Drug)
Ipatasertib + Abiraterone
Experimental
Participants received Ipatasertib plus Abiraterone (along with Prednisone/Prednisolone), administered orally in 28-day cycles.
干预措施: Abiraterone (Drug)
Ipatasertib + Abiraterone
Experimental
Participants received Ipatasertib plus Abiraterone (along with Prednisone/Prednisolone), administered orally in 28-day cycles.
干预措施: Prednisone/Prednisolone (Drug)
结局指标
主要结局
Investigator-assessed Radiographic Progression-free Survival (rPFS), Per Prostate Cancer Working Group 3 (PCWG3) Criteria in Phosphatase and Tensin Homolog (PTEN) Loss Population
时间窗: Up to approximately 32 months
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.
Investigator-assessed rPFS, Per PCWG3 Criteria in ITT Population
时间窗: Up to approximately 32 months
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.
次要结局
- Overall Survival (OS) in PTEN-loss Population(Up to approximately 6.5 years)
- OS in ITT Population(Up to approximately 6.5 years)
- Time to Pain Progression in PTEN-loss Population(Up to approximately 5.5 years)
- Time to Pain Progression in ITT Population(Up to approximately 5.5 years)
- Time to Initiation of Cytotoxic Chemotherapy for Prostate Cancer (PC) in PTEN-loss Population(Up to approximately 5.5 years)
- Time to Initiation of Cytotoxic Chemotherapy for PC in ITT Population(Up to approximately 5.5 years)
- Time to Function Deterioration Per European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) Physical Function (PF) Scale and Role Function (RF) Scale in PTEN-loss Population(Up to approximately 5.5 years)
- Time to Function Deterioration Per EORTC QLQ-C30 PF Scale and RF Scale in ITT Population(Up to approximately 5.5 years)
- Time to Prostate-specific Antigen (PSA) Progression, Per the PCWG3 Criteria in PTEN-loss Population(Up to approximately 5.5 years)
- Time to PSA Progression, Per the PCWG3 Criteria in ITT Population(Up to approximately 5.5 years)
- Time to First Opioid Use in PTEN-loss Population(Up to approximately 5.5 years)
- Time to First Opioid Use in ITT Population(Up to approximately 5.5 years)
- Time to Symptomatic Skeletal Event (SSE) in PTEN-loss Population(Up to approximately 5.5 years)
- Time to SSE in ITT Population(Up to approximately 5.5 years)
- Objective Response Rate (ORR) Per RECIST V1.1 and PCWG3 Criteria in Participants With Measurable Disease in PTEN-loss Population(Up to approximately 5.5 years)
- ORR Per RECIST V1.1 and PCWG3 Criteria in Participants With Measurable Disease in ITT Population(Up to approximately 5.5 years)
- Duration of Confirmed Response (DOCR) in PTEN-loss Population(Up to approximately 5.5 years)
- DOCR in ITT Population(Up to approximately 5.5 years)
- PSA Response Rate in PTEN-loss Population(Up to approximately 5.5 years)
- PSA Response Rate in ITT Population(Up to approximately 5.5 years)
- Investigator-assessed rPFS Per PCWG3 Criteria in PTEN-loss Population by Next-generation Sequencing (NGS)(Up to approximately 32 months)
- Percentage of Participants With Adverse Events (AEs)(Up to 28 days after last study drug administration (approximately 6.5 years))
- Plasma Concentrations of Ipatasertib at Specified Timepoints(1-3 hours post-dose (Cycle 1, Day 1; Cycle 1 Day 15 and Cycle 3 Day 1) and pre-dose at steady state (Cycle 1 Day 15, Cycle 3 Day 1, Cycle 6 Day 1) (each cycle length= 28 days))
- Plasma Concentrations of Abiraterone at Specified Timepoints(Pre-dose at steady state in Cycle 1, Day 15 and Cycle 3 Day 1 (each cycle length= 28 days))
研究者
研究点 (176)
Loading locations...
相似试验
终止
1 期
A Study Evaluating The Safety, Efficacy and Pharmacokinetics Of Ipatasertib In Combination With Atezolizumab And Docetaxel In Metastatic Castration-Resistant Prostate Cancer (mCRPC).Castration-Resistant Prostatic CancerNCT04404140Hoffmann-La Roche6
进行中（未招募）
1 期
Testing the Addition of Ipatasertib to the Usual Chemotherapy Treatment (Paclitaxel and Carboplatin) for Stage III or IV Epithelial Ovarian CancerFallopian Tube Endometrioid AdenocarcinomaFallopian Tube High Grade Serous AdenocarcinomaOvarian Endometrioid AdenocarcinomaOvarian High Grade Serous AdenocarcinomaPrimary Peritoneal Endometrioid AdenocarcinomaPrimary Peritoneal High Grade Serous AdenocarcinomaStage III Fallopian Tube Cancer AJCC v8Stage III Ovarian Cancer AJCC v8Stage III Primary Peritoneal Cancer AJCC v8Stage IV Fallopian Tube Cancer AJCC v8Stage IV Ovarian Cancer AJCC v8Stage IV Primary Peritoneal Cancer AJCC v8Unresectable Fallopian Tube Endometrioid AdenocarcinomaUnresectable Fallopian Tube High Grade Serous AdenocarcinomaUnresectable Ovarian Endometrioid AdenocarcinomaUnresectable Ovarian High Grade Serous AdenocarcinomaUnresectable Primary Peritoneal Endometrioid AdenocarcinomaUnresectable Primary Peritoneal High Grade Serous AdenocarcinomaNCT05276973National Cancer Institute (NCI)25
终止
1 期
A Study of Ipatasertib Plus Palbociclib and Fulvestrant Versus Placebo Plus Palbociclib and Fulvestrant in Hormone Receptor Positive and HER2 Negative Locally Advanced Unresectable or Metastatic Breast CancerBreast CancerNCT04060862Hoffmann-La Roche20
已完成
3 期
A Study of Ipatasertib in Combination With Atezolizumab and Paclitaxel as a Treatment for Participants With Locally Advanced or Metastatic Triple-Negative Breast CancerTriple-Negative Breast CancerNCT04177108Hoffmann-La Roche242
已完成
1 期
Ipatasertib + Pertuzumab +Trastuzumab in Advanced HER2+ PI3KCA-mutant Breast Cancer PatientsMetastatic Breast CancerNCT04253561SOLTI Breast Cancer Research Group17