NCT05348577进行中（未招募）3 期
A Phase III Double-Blind, Randomised, Placebo-Controlled Study Assessing the Efficacy and Safety of Capivasertib + Docetaxel Versus Placebo + Docetaxel as Treatment for Patients With Metastatic Castration Resistant Prostate Cancer (mCRPC)
适应症
干预措施
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- AstraZeneca
- 入组人数
- 1,035
- 试验地点
- 1
- 主要终点
- Overall Survival (OS) in the overall population
研究概览
简要总结
This study will assess the efficacy and safety of capivasertib plus docetaxel versus placebo plus docetaxel in participants with metastatic castration resistant prostate cancer (mCRPC), all participants will receive the docetaxel with steroid therapy and receive androgen deprivation therapy. The intention of the study is to demonstrate that the combination of capivasertib plus docetaxel is superior to placebo plus docetaxel with respect to the overall survival and/or the radiographic progression free survival of study participants.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
The study is double-blinded, neither the patients nor the investigator will know what study intervention was assigned.
Capivasertib and placebo film-coated tablets will be identical in appearance and presented in the same packaging to ensure blinding of the capivasertib.
All personnel involved with the statistical analysis of the study will remain blinded until database lock and CSP deviations have been identified.
入排标准
- 年龄范围
- 18 Years 至 130 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Histologically-confirmed prostate adenocarcinoma without predominant neuroendocrine or small cell cancers
- •Metastatic disease documented prior to randomisation by clear evidence of ≥ 1 bone lesion (defined as 1 lesion with positive uptake on bone scan) and/or ≥ 1 soft tissue lesion (measurable or non-measurable)
- •Patient must have been previously treated with a next generation hormonal agent (NHA), ie, abiraterone, enzalutamide, apalutamide or darolutamide, for prostate cancer for at least 3 months and shown evidence of disease progression (radiological or via PSA assessment) while receiving the NHA
- •Evidence of mCRPC with progression of disease despite androgen deprivation therapy (ADT)
- •Serum testosterone level ≤ 50 ng/dL
- •Candidate for docetaxel and steroid therapy
- •Ongoing ADT with LHRH agonist, LHRH antagonist, or bilateral orchiectomy
- •Eastern Cooperative Oncology Group (ECOG)/World Health Organisation (WHO) performance status 0 to 1 and anticipated minimum life expectancy of 12 weeks
- •Confirmation that archival formalin-fixed paraffin-embedded (FFPE) tumour tissue sample which meets the minimum pathology and sample requirements is available to send to the central laboratory
- •Able and willing to swallow and retain oral medication
- •Agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm
排除标准
- •Radiotherapy with a wide field of radiation within 4 weeks before start of study treatment
- •Major surgery (excl. placement of vascular access, transurethral resection of prostate, bilateral orchiectomy, internal stents) within 4 weeks of start of study treatment
- •Brain metastases,or spinal cord compression (unless spinal cord compression is asymptomatic and stable and not requiring steroids for at least 4 weeks prior to start of study treatment)
- •Any of the following cardiac criteria:
- •i. Mean resting corrected QT interval (QTc) >470 msec from 3 consecutive ECGs ii. Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG iii. Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, potential for torsades de pointes, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age,or any concomitant medication known to prolong the QT interval iv. Experience of any of the following procedures or conditions in the preceding 3 months: coronary artery bypass graft, vascular stent, myocardial infarction, unstable angina pectoris, congestive heart failure NYHA Grade ≥2 v. Symptomatic hypotension - systolic blood pressure <90 mmHg and/or diastolic blood pressure <50 mmHg vi. haemodinamic instability
- •Clinically significant abnormalities of glucose metabolism as defined by any of the following:
- •i. Patients with diabetes mellitus (DM) type 1 or DM type 2 requiring insulin treatment ii. HbA1c ≥8.0% (63.9 mmol/mol)
- •Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values:
- •i. Absolute neutrophil count < 1.5x 10^9/L ii. Platelet count < 100x 10^9/L iii. Haemoglobin < 9 g/dL (< 5.59 mmol/L) iv. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) > 2.5x upper limit of normal (ULN) if no demonstrable liver metastases or > 5x ULN in the presence of liver metastases. Elevated alkaline phosphatase (ALP) is not exclusionary if due to the presence of bone metastases and liver function is otherwise considered adequate in the investigator's judgement v. Total bilirubin > 1.5x ULN (participants with confirmed Gilbert's syndrome may be included in the study with a higher value) vi. Creatinine clearance < 50 mL/min per the Cockcroft and Gault formula without the need for chronic dialysis;
- •As judged by the investigator, any evidence of diseases (including severe or uncontrolled systemic diseases, uncontrolled hypertension, history of interstitial pneumonia / pneumonitis or interstitial lung disease, renal transplant and active bleeding diseases), which, in the investigator's opinion, makes it undesirable for the patient to participate in the study or that would jeopardise compliance with the protocol.
- •Refractory nausea and vomiting, malabsorption syndrome, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection, or other condition that would preclude adequate absorption of capivasertib
- •Any other disease, physical examination finding, or clinical laboratory finding that, in the investigator's opinion, gives reasonable suspicion of a disease or condition that contra-indicates the use of an investigational drug, may affect the interpretation of the results, render the patient at high risk from treatment complications or interferes with obtaining informed consent. Evidence of dementia, altered mental status, or any psychiatric condition that would prohibit understanding or rendering of informed consent.
- •Previous allogeneic bone marrow transplant or solid organ transplant
- •History of another primary malignancy except for malignancy treated with curative intent with no known active disease ≥2 years before the first dose of study intervention and of low potential risk for recurrence. Exceptions include adequately resected non-melanoma skin cancer and curatively treated in situ disease.
- •Persistent toxicities (CTCAE Grade ≥2) caused by previous anticancer therapy, excluding alopecia. Patients with irreversible toxicity that is not reasonably expected to be exacerbated by study intervention in the opinion of the investigator may be included (eg, hearing loss)
- •Known to have active hepatitis infection.
- •Known to have human immunodeficiency virus (HIV) with a detectable viral RNA load or a CD4+ T-cell count < 350 cells/uL or a history of an acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection within the past 12 months, or receiving anti-HIV medications for less than 4 weeks.
- •Known to have active tuberculosis infection (clinical evaluation that may include clinical history, physical examination and radiographic findings, or tuberculosis testing in line with local practice).
- •Treatment with any of the following:
- •i. Prior chemotherapy for CRPC. Chemotherapy for metastatic or localized HSPC (including docetaxel) is allowed provided that chemotherapy was completed ≥ 6months before randomisation and progression of the prostate cancer occurred ≥ 6months after the completion of therapy.
- •ii. Prior exposure to AKT inhibitors or PI3K inhibitors iii. Any investigational agents or study drugs from a previous clinical study within 30 days or 5 half-lives (whichever is longer) of the first dose of study treatment iv. Any other immunotherapy, immunosuppressant medication (other than corticosteroids) or anticancer agents (except ADT) within 3 weeks of the first dose of study treatment v. Strong inhibitors or strong inducers of cytochrome P450 (CYP)3A4 within 2 weeks prior to the first dose of study treatment (3 weeks for St John's wort), vi.Use of any live vaccine administration 30 days prior to the initiation of study treatment, during, and for at least 90 days after the last dose of the study treatment
- •Drugs known to significantly prolong the QT interval and associated with Torsade de Pointes within 5 half-lives of the first dose of study treatment
- •History of hypersensitivity to active or inactive excipients of capivasertib, docetaxel, or drugs with a similar chemical structure or class
- •Any restriction or contraindication based on the local prescribing information that would prohibit the use of docetaxel
研究组 & 干预措施
capivasertib + docetaxel
Experimental
Participants receive capivasertib in combination with docetaxel and steroids on a background of ADT.
干预措施: capivasertib (Drug)
capivasertib + docetaxel
Experimental
Participants receive capivasertib in combination with docetaxel and steroids on a background of ADT.
干预措施: docetaxel (Drug)
placebo + docetaxel
Placebo Comparator
Participants receive placebo in combination with docetaxel and steroids on a background of ADT.
干预措施: docetaxel (Drug)
placebo + docetaxel
Placebo Comparator
Participants receive placebo in combination with docetaxel and steroids on a background of ADT.
干预措施: placebo (Other)
结局指标
主要结局
Overall Survival (OS) in the overall population
时间窗: up to approximately 46 months
Overall survival is defined as time from randomisation until the date of death due to any cause.
Radiographic Progression-free Survival (rPFS) in the overall population
时间窗: up to approximately 37 months
Radiographic Progression-free Survival (rPFS) is defined as time from randomization to radiographic progression as assessed by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) for soft tissue and/or Prostate Cancer Working Group 3 (PCWG3) for bone or death due to any cause
次要结局
- Radiographic Progression-free Survival (rPFS) in patients with mCRPC and PTEN-deficient tumours (IHC)(up to approximately 37 months)
- Overall Survival (OS) in patients with mCRPC and PTEN-proficient tumours (IHC)(up to approximately 46 months)
- Overall Pain Severity and Pain Interference as assessed by BPI-SF questionnaire in the overall population(up to approximately 37 months)
- Overall Survival (OS) in patients with mCRPC and PTEN-deficient tumours (IHC).(up to approximately 46 months)
- Radiographic Progression-free Survival (rPFS) in patients with mCRPC and PTEN-proficient tumours (IHC)(up to approximately 37 months)
- Time to pain progression (TTPP) in the overall population(up to approximately 37 months)
- Time to first Symptomatic Skeletal-Related Event (SSRE) in the overall population(up to approximately 46 months)
- Plasma concentration of capivasertib derived from a population PK model in the overall population(pre dose (up to 90 minutes prior) and post dose (1 hour, 2 hours and 4 hours post dose))
- Time to deterioration in urinary symptoms (TTDUS) in the overall population(up to approximately 37 months)
- Time to deterioration in Physical Functioning (TTDPF) in the overall population(up to approximately 37 months)
研究者
研究点 (1)
Loading locations...
相似试验
进行中（未招募）
3 期
Capivasertib+Paclitaxel as First Line Treatment for Patients With Locally Advanced or Metastatic TNBCTriple Negative Breast NeoplasmsNCT03997123AstraZeneca923
招募中
3 期
TCb vs EC-T in High Risk ER+/HER2- Breast CancerHormone Receptor Positive HER-2 Negative Breast CancerNCT05901428Fudan University1,736
进行中（未招募）
3 期
Capivasertib+Fulvestrant vs Placebo+Fulvestrant as Treatment for Locally Advanced (Inoperable) or Metastatic HR+/HER2- Breast CancerLocally Advanced (Inoperable) or Metastatic Breast CancerNCT04305496AstraZeneca818
已完成
3 期
A Study of Ipatasertib in Combination With Paclitaxel as a Treatment for Participants With PIK3CA/AKT1/PTEN-Altered, Locally Advanced or Metastatic, Triple-Negative Breast Cancer or Hormone Receptor-Positive, HER2-Negative Breast CancerBreast CancerNCT03337724Hoffmann-La Roche579
终止
2 期
Docetaxel and Capecitabine With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and NeckHead and Neck Squamous Cell CarcinomaNCT02524275University of Nebraska14