A Phase 3, Randomized, Open-Label, Controlled Study of Cabozantinib (XL184) in Combination With Atezolizumab vs Second Novel Hormonal Therapy (NHT) in Subjects With Metastatic Castration-Resistant Prostate Cancer
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- Exelixis
- 入组人数
- 575
- 试验地点
- 279
- 主要终点
- Duration of Progression Free Survival (PFS) Per Response Evaluable Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Blinded Independent Radiology Committee (BIRC)
研究概览
简要总结
This is a Phase 3, multi-center, randomized, open-label, controlled study designed to evaluate the safety and efficacy of cabozantinib given in combination with atezolizumab versus a second novel hormonal therapy (NHT) in men with metastatic castration-resistant prostate cancer (mCRPC) who have previously been treated with one, and only one, NHT for their prostate cancer disease.
详细描述
The primary objective of this study is to evaluate the efficacy of cabozantinib (XL184) in combination with atezolizumab versus a second NHT (abiraterone or enzalutamide) in subjects with mCRPC who have previously been treated with one, and only one, NHT (e.g. abiraterone, apalutamide, darolutamide, or enzalutamide) to treat metastatic castration-sensitive prostate cancer (mCSPC), non-metastatic CRPC (M0 CRPC), or mCRPC, and who have measurable extrapelvic disease. The multiple primary efficacy endpoints comparing the experimental arm and control arm are Duration of Progression Free Survival (PFS) per RECIST 1.1 by Blinded Independent Radiology Committee (BIRC) and Duration of Overall Survival (OS). The secondary efficacy endpoint is Objective Response Rate (ORR) per RECIST 1.1 per BIRC.
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
- None
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
- •Men with histologically or cytologically confirmed adenocarcinoma of the prostate
- •Prior treatment with one, and only one, NHT (eg, abiraterone, apalutamide, darolutamide, or enzalutamide) for castration-sensitive locally advanced (T3 or T4) or mCSPC, M0 CRPC, or mCRPC
- •Surgical or medical castration, with serum testosterone ≤ 50 ng/dL (≤ 1.73 nmol/L) at screening
- •Measurable (extrapelvic soft tissue) metastatic disease per Investigator assessment defined by at least one of the following: measurable visceral disease (eg, adrenal, kidney, liver, lung, pancreas, spleen) per RECIST 1.1; OR measurable extrapelvic adenopathy (ie, adenopathy above the aortic bifurcation)
- •Progressive disease at study entry as defined by specific criteria for prostate specific antigen (PSA) progression OR soft tissue disease progression in the opinion of the Investigator (Note: subjects with bone disease progression alone are not eligible)
- •Age ≥ 18 years old or meeting country definition of adult, whichever is older, on the day of consent
- •ECOG performance status of 0 or 1
- •Recovery to baseline or ≤ Grade 1 per Common Terminology Criteria for Adverse Events (CTCAE) v5 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy in the opinion of the Investigator
- •Adequate organ and marrow function based upon specific laboratory assessments obtained within 21 days prior to randomization
- •Understanding and ability to comply with protocol requirements
排除标准
- •Any prior nonhormonal therapy initiated for the treatment of mCRPC
- •Receipt of abiraterone within 1 week; cyproterone within 10 days; or flutamide, nilutamide, bicalutamide, enzalutamide, or other androgen-receptor inhibitors within 2 weeks before randomization
- •Radiation therapy within 4 weeks (2 weeks for bone metastases) prior to randomization (subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible)
- •Known brain metastases or cranial epidural disease unless adequately treated and clinically stable at least 4 weeks prior to randomization
- •Symptomatic or impending spinal cord compression or cauda equina syndrome
- •Concomitant anticoagulation with oral anticoagulants (some specific exceptions apply)
- •Administration of a live, attenuated vaccine within 30 days prior to randomization
- •Systematic treatment with, or any condition requiring, either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days prior to randomization
- •Uncontrolled, significant intercurrent or recent illness
- •Major surgery within 4 weeks prior to randomization
- •Corrected QT interval calculated by the Fridericia formula (QTcF) > 480 ms per ECG within 21 days before randomization
- •Inability or unwillingness to swallow pills or receive IV administration
- •Previously identified allergy or hypersensitivity to components of the study treatment formulations or history of severe infusion-related reactions to monoclonal antibodies
- •Any other active malignancy at time of randomization or diagnosis of another malignancy within 2 years prior to randomization that requires active treatment (some exceptions apply such as locally curable cancers that have apparently been cured).
研究组 & 干预措施
Control Arm
Subjects with mCRPC will receive active comparator of EITHER abiraterone 1000mg oral, qd + prednisone 5 mg oral, bid; OR enzalutamide 160mg oral, qd as designated by the Investigator prior to randomization
干预措施: Enzalutamide (Drug)
Experimental Arm
Subjects with mCRPC will receive cabozantinib 40mg oral, qd + atezolizumab 1200mg infusion, q3w
干预措施: Cabozantinib (Drug)
Experimental Arm
Subjects with mCRPC will receive cabozantinib 40mg oral, qd + atezolizumab 1200mg infusion, q3w
干预措施: Atezolizumab (Drug)
Control Arm
Subjects with mCRPC will receive active comparator of EITHER abiraterone 1000mg oral, qd + prednisone 5 mg oral, bid; OR enzalutamide 160mg oral, qd as designated by the Investigator prior to randomization
干预措施: Abiraterone Acetate (Drug)
Control Arm
Subjects with mCRPC will receive active comparator of EITHER abiraterone 1000mg oral, qd + prednisone 5 mg oral, bid; OR enzalutamide 160mg oral, qd as designated by the Investigator prior to randomization
干预措施: Prednisone (Drug)
结局指标
主要结局
Duration of Progression Free Survival (PFS) Per Response Evaluable Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Blinded Independent Radiology Committee (BIRC)
时间窗: Up to a maximum of approximately 30 months (Median duration of follow-up was 14.31 months)
Duration of PFS was defined as the time from randomization to the earlier of either the date of radiographic progression (defined as progressive disease \[PD\] per RECIST 1.1) per BIRC or the date of death due to any cause. PD was defined as at least a 20% increase in the sum of diameters of target lesions, with an absolute increase of ≥ 5 mm, unequivocal progression of non-target lesions and/or the appearance of new lesions.
Duration of Overall Survival (OS)
时间窗: Up to a maximum of approximately 45 months (Median duration of follow-up was 24.05 months)
Duration of OS was defined as the time from randomization to death due to any cause. For participants, who were not known to have died at the time of data cutoff and were permanently lost to follow-up, duration of OS was censored at the earlier of the following dates: date the participant was last known to be alive or date of full withdrawal of consent (including survival follow-up), or date of data cutoff. OS was calculated as earlier of date of death or censoring - date of randomization + 1)/30.4375
次要结局
未报告次要终点