2023-506153-38-00招募中3 期
A Randomized, Double-blind, Placebo-controlled, Phase 3 Study of Apalutamide in Subjects with High-risk, Localized or Locally Advanced Prostate Cancer Who are Candidates for Radical Prostatectomy
干预措施
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 668
- 试验地点
- 69
- 主要终点
- pCR rate (as defined in the pathology charter and assessed by a pathology blinded independent central review [BICR])
研究概览
简要总结
To determine if treatment with apalutamide plus ADT before and after RP with pLND in subjects with high-risk localized or locally advanced prostate cancer results in an improvement in pCR rate and MFS based on conventional or PSMA PET imaging, as compared to placebo plus ADT
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Must be ≥18 years of age
- •Criterion modified per Amendment 1 10.
- •Criterion modified per Amendment 2 10.
- •Criterion modified per Amendment 7 10.
- •Contraceptive use by male subjects (and female partners of male subjects enrolled in the study who are of childbearing potential or are pregnant) should be consistent with local regulations regarding the use of contraceptive methods for subjects participating in clinical studies.
- •Signed an informed consent form (ICF) indicating that the subject understands the purpose of and procedures required for the study and is willing to participate in the study; subjects must be willing and able to adhere to the prohibitions and restrictions specified in this protocol (Section 4.3)
- •Histologically confirmed adenocarcinoma of the prostate
- •Criterion modified per Amendment 1 4.
- •Criterion modified per Amendment 2 4.2 High risk disease defined by a total Gleason Sum Score ≥4+3 (=Grade Groups [GG] 3 5) and ≥1 of the following 4 criteria: • Any combination of Gleason Score 4+3 (=GG 3) and Gleason Score 8 (4+4 or 5+3) in ≥6 systematic cores (with ≥1 core Gleason Score 8 [4+4 or 5+3] included); • Any combination of Gleason Score 4+3 (=GG 3) and Gleason Score 8 (4+4 or 5+3) in ≥3 systematic cores and PSA ≥20 ng/mL (with ≥1 core Gleason Score 8 [4+4 or 5+3] included); • Gleason Score ≥9 (=GG 5) in at least 1 systematic or targeted core; or • At least 2 systematic or targeted cores with continuous Gleason Score ≥8 (=GG 4), each with ≥80% involvement
- •Criterion modified per Amendment 1 5.
- •Candidate for RP with pLND as per the investigator
- •Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1
- •Criterion modified per Amendment 1 7.
- •Criterion modified per Amendment 2 7.
- •Adequate organ function determined by the following central laboratory values: a. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin within normal limits, ie, ≤ the upper limit of normal ([ULN]; note that in subjects with Gilbert's syndrome, if total bilirubin is >1.5 X ULN, measure direct and indirect bilirubin. If direct bilirubin is ≤1.5 X ULN, the subject may be eligible); b. Serum creatinine <1.8 mg/dL; c. Platelets ≥75,000/microliter, without transfusion and/or growth factors within 1 month prior to randomization; d. Hemoglobin ≥12.0 g/dL (7.4 mmol), without transfusion and/or growth factors within 1 month prior to randomization
- •Criterion modified per Amendment 4 8.1 Able to receive ADT for at least 13 months, based on cardiovascular risk assessment and the investigator's assessment
- •Criterion modified per Amendment 1 9.
- •Be able to swallow whole study drug tablets
排除标准
- •Distant metastasis based on conventional imaging (clinical stage M1). Nodal disease below the iliac bifurcation (clinical stage N1) is not an exclusion. Diagnosis of distant metastasis (clinical M stage; M0 versus M1a, M1b, M1c) and pelvic nodal disease (clinical N stage; N1 versus N0) will be assessed by central radiological review. Patients are considered eligible only if the central radiological review confirms clinical stage M0
- •Human immunodeficiency virus-positive subjects with 1 or more of the following: a. Not receiving highly active antiretroviral therapy b. Had a change in antiretroviral therapy within 6 months of the start of screening c. Receiving antiretroviral therapy that may interfere with study drug (consult sponsor for review of medication prior to enrollment) d. CD4 count <350 at screening e. AIDS-defining opportunistic infection within 6 months of start of screening
- •Active or symptomatic viral hepatitis or chronic liver disease; ascites or bleeding disorders secondary to hepatic dysfunction
- •Criterion modified per Amendment 2 12.
- •History of seizure; any condition that may predispose to seizure (including, but not limited to, prior stroke, transient ischemic attack, or loss of consciousness ≤1 year prior to randomization); presence of brain arteriovenous malformation; or intracranial masses such as schwannomas and meningiomas that are causing edema or mass effect
- •Treatment with drugs known to lower the seizure threshold within 4 weeks prior to randomization
- •Gastrointestinal conditions affecting absorption
- •Criterion modified per Amendment 1 15.
- •Known or suspected contraindications or hypersensitivity to apalutamide, GnRHa or any of the components of the formulations
- •Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject
- •Criterion modified per Amendment 2 17.
- •Active malignancies (ie, progressing or requiring treatment or treatment change in the last 24 months) other than prostate cancer. The only allowed exceptions are: non-muscle invasive bladder cancer (NMIBC); skin cancer (non-melanoma or melanoma) treated within the last 24 months that is considered completely cured; breast cancer (adequately treated lobular carcinoma in situ or ductal carcinoma in situ, or history of localized breast cancer and receiving antihormonal agents and considered to have a very low risk of recurrence); malignancy that is considered cured with minimal risk of recurrence.
- •Criterion modified per Amendment 2 2.
- •(a) Prior treatment with androgen receptor antagonists. (b) Treatment with GnRHa prior to ICF signature.
- •Criterion deleted per Amendment 1
- •Criterion deleted per Amendment 1
- •Bilateral orchiectomy
- •Criterion modified per Amendment 1 6.
- •Criterion modified per Amendment 2 6.
- •History of prior systemic or local therapy for prostate cancer, including pelvic radiation for prostate cancer
- •Criterion modified per Amendment 1 7.
- •Use of any investigational agent ≤4 weeks prior to randomization or any therapeutic procedure for prostate cancer at any time
- •Major surgery ≤4 weeks prior to randomization
- •Criterion modified per Amendment 4 9.1 Any of the following within 12 months prior to first dose of study drug: severe or unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events (eg, pulmonary embolism, cerebrovascular accident including transient ischemic attacks), or clinically significant ventricular arrhythmias or New York Heart Association Class II to IV heart disease; uncomplicated deep vein thrombosis is not considered exclusionary
研究组 & 干预措施
-
Auxiliary
Participants receiving -
干预措施: - (Drug)
-, -
Auxiliary
Participants receiving -, -
干预措施: - (Drug)
结局指标
主要结局
pCR rate (as defined in the pathology charter and assessed by a pathology blinded independent central review [BICR])
pCR rate (as defined in the pathology charter and assessed by a pathology blinded independent central review [BICR])
MFS based on conventional or PSMA PET imaging (defined as the time from randomization to the date of the first occurrence of radiographic distant metastasis on conventional [ie, CT/MRI and bone scan] or PSMA PET imaging evaluated by radiology BICR, pathologic finding of distant metastasis, or death from any cause, whichever occurs first).
MFS based on conventional or PSMA PET imaging (defined as the time from randomization to the date of the first occurrence of radiographic distant metastasis on conventional [ie, CT/MRI and bone scan] or PSMA PET imaging evaluated by radiology BICR, pathologic finding of distant metastasis, or death from any cause, whichever occurs first).
次要结局
未报告次要终点
研究者
CTIS Point of Contact
Scientific
Janssen - Cilag International
研究点 (69)
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