ProBio: An Outcome-adaptive and Randomized Multi-arm Biomarker Driven Study in Patients With Metastatic Prostate Cancer
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 750
- 试验地点
- 32
- 主要终点
- Progression free survival (PFS) in mCRPC
研究概览
简要总结
ProBio is an international, outcome-adaptive, multi-arm, open-label, multiple assignment randomized biomarker driven platform trial in patients with metastatic prostate cancer. Patients will be randomized to control or experimental treatment arms. Patients in the control arm will receive standard of care following national guidelines. Patients in the experimental arm will be randomized to treatments based on a biomarker signature inferred from diagnostic tissue or liquid biopsy profiling. The predefined biomarker signatures are tumor properties or mutations in genes/pathways with previously demonstrated clinical validity (e.g. prognostic value or association with treatment response). The biomarker signatures are identified using a hybridisation capture gene panel specifically designed for prostate cancer.
详细描述
ProBio is an outcome-adaptive, multi-arm, open-label, multiple assignment randomised biomarker driven platform trial in patients with metastatic hormone-sensitive and castration-resistant prostate cancer.
Patients will be randomised to control or experimental treatment class arms. Patients in the control arm will receive standard of care following national guidelines and will remain within the control arm throughout the course of the trial. Patients in the experimental arm will be randomised to a treatment class (consisting of one or multiple drugs) based on a biomarker signature. The biomarker signatures are defined as tumour properties or mutations in certain genes/pathways identified in the scientific literature as important in prostate cancer treatment response. The biomarker signatures are identified using a gene panel specifically designed for advanced prostate cancer.
Alterations in the following genes/pathways or combinations thereof constitute the biomarker signatures:
- Androgen receptor
- DNA-repair deficiency
- TP53
- TMPRSS2-ERG gene fusion
- PI3K pathway alterations
Patients in the experimental arm can be randomized to the following treatments classes:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 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
- •Man with histologically confirmed prostate adenocarcinoma, initiating systemic therapy for metastatic disease, encompassing newly diagnosed (i.e. de novo) hormone sensitive prostate cancer (mHSPC) or first-line castration resistant prostate cancer (mCRPC)
- •Distant metastatic disease documented by positive bone scan or metastatic lesions on CT or MRI
- •Adequate health as assessed by the investigator to receive all available treatments in the trial
- •ECOG/WHO (Eastern Cooperative Oncology Group/ World Health Organization) performance score 0-2
- •Adequate organ and bone marrow function
- •Albumin greater than or equal to 28 g/L
- •Able to understand the patient information and sign written informed consent
排除标准
- •Other malignancies within 5 years except non-melanoma skin cancer
- •Within 6 months of randomization: myocardial infarction, unstable angina, angioplasty, bypass surgery, stroke, TIA (transient ischemic attack), or congestive heart failure NYHA (New York Heart Association) class III or IV
- •Uncontrolled hypertension
- •Uncontrolled hypotension
- •Received systemic therapy (with the exception of standard ADT) prior to study inclusion, for the CRPC indication
- •Any severe acute or chronic medical condition that places the patient at increased risk of serious toxicity or interferes with the interpretation of study results
- •Unable to comply with study procedures
- •Current participation in another clinical trial that will be in conflict with the present study, administration of an investigational therapeutic or invasive surgical procedure within 28 days prior to study enrolment
- •Patients who are unlikely to comply with the protocol
- •Any condition or situation which, in the opinion of the investigator, would put the subject at risk, may confound study results, or interfere with the subjects participation in this study.
- •Any medical condition that would make use of the study treatments contraindicated, according to the SmPC, e.g. significant heart or liver disease.
研究组 & 干预措施
Control: Standard Care
Randomization between assignment to the control arm or the biomarker driven arm will be stratified on biomarker signatures, previous treatment, and fraction of ctDNA and will therefore occur after the results from the ctDNA profiling is obtained. Patients in the control arm will receive standard of care following national guidelines.
干预措施: Enzalutamide Oral Capsule (Drug)
Control: Standard Care
Randomization between assignment to the control arm or the biomarker driven arm will be stratified on biomarker signatures, previous treatment, and fraction of ctDNA and will therefore occur after the results from the ctDNA profiling is obtained. Patients in the control arm will receive standard of care following national guidelines.
干预措施: Abiraterone Oral Tablet (Drug)
Control: Standard Care
Randomization between assignment to the control arm or the biomarker driven arm will be stratified on biomarker signatures, previous treatment, and fraction of ctDNA and will therefore occur after the results from the ctDNA profiling is obtained. Patients in the control arm will receive standard of care following national guidelines.
干预措施: Cabazitaxel 60 mg Solution for Injection (Drug)
Control: Standard Care
Randomization between assignment to the control arm or the biomarker driven arm will be stratified on biomarker signatures, previous treatment, and fraction of ctDNA and will therefore occur after the results from the ctDNA profiling is obtained. Patients in the control arm will receive standard of care following national guidelines.
干预措施: Docetaxel Injectable Solution (Drug)
Control: Standard Care
Randomization between assignment to the control arm or the biomarker driven arm will be stratified on biomarker signatures, previous treatment, and fraction of ctDNA and will therefore occur after the results from the ctDNA profiling is obtained. Patients in the control arm will receive standard of care following national guidelines.
干预措施: Radium Chloride Ra-223 (Drug)
Control: Standard Care
Randomization between assignment to the control arm or the biomarker driven arm will be stratified on biomarker signatures, previous treatment, and fraction of ctDNA and will therefore occur after the results from the ctDNA profiling is obtained. Patients in the control arm will receive standard of care following national guidelines.
干预措施: Apalutamide (Drug)
Treatment 1 in mHSPC: AR signalling inhibitors (ARSi)
Assignments to therapy in the biomarker driven arms will be done on the basis of the biomarker signature using the current information about the efficacy of the various regimens for that signature. Information from previous studies may be incorporated in the randomization at study onset if such reliable data exists. Specifically, patients with an intact androgen receptor (AR) and without TP53 mutations will have increased chance of being randomized to treatment with ARSi.
干预措施: Enzalutamide Oral Capsule (Drug)
Treatment 1 in mHSPC: AR signalling inhibitors (ARSi)
Assignments to therapy in the biomarker driven arms will be done on the basis of the biomarker signature using the current information about the efficacy of the various regimens for that signature. Information from previous studies may be incorporated in the randomization at study onset if such reliable data exists. Specifically, patients with an intact androgen receptor (AR) and without TP53 mutations will have increased chance of being randomized to treatment with ARSi.
干预措施: Abiraterone Oral Tablet (Drug)
Treatment 1 in mHSPC: AR signalling inhibitors (ARSi)
Assignments to therapy in the biomarker driven arms will be done on the basis of the biomarker signature using the current information about the efficacy of the various regimens for that signature. Information from previous studies may be incorporated in the randomization at study onset if such reliable data exists. Specifically, patients with an intact androgen receptor (AR) and without TP53 mutations will have increased chance of being randomized to treatment with ARSi.
干预措施: Apalutamide (Drug)
Treatment 2 in mHSPC: taxane-based chemotherapy in combination with ARSi
Patients with TP53 mutations and TMPRSS2-ERG gene fusions will have an increased chance of being randomised to treatment with chemotherapy plus an ARSi.
干预措施: Abiraterone Oral Tablet (Drug)
Treatment 2 in mHSPC: taxane-based chemotherapy in combination with ARSi
Patients with TP53 mutations and TMPRSS2-ERG gene fusions will have an increased chance of being randomised to treatment with chemotherapy plus an ARSi.
干预措施: Docetaxel Injectable Solution (Drug)
Treatment 2 in mHSPC: taxane-based chemotherapy in combination with ARSi
Patients with TP53 mutations and TMPRSS2-ERG gene fusions will have an increased chance of being randomised to treatment with chemotherapy plus an ARSi.
干预措施: Darolutamide (Drug)
Treatment 3 in mHSPC: Poly ADP Ribose Polymerase (PARP) inhibitor
DNA-repair deficient patients will have an increased chance of receiving PARP inhibitors at study onset.
干预措施: Niraparib plus Abiraterone acetate plus Prednisone (Drug)
Treatment 1 in mCRPC: AR signalling inhibitors (ARSi)
Specifically, patients with an intact androgen receptor (AR) and without TP53 mutations will have increased chance of being randomized to treatment with ARSi.
干预措施: Enzalutamide Oral Capsule (Drug)
Treatment 1 in mCRPC: AR signalling inhibitors (ARSi)
Specifically, patients with an intact androgen receptor (AR) and without TP53 mutations will have increased chance of being randomized to treatment with ARSi.
干预措施: Abiraterone Oral Tablet (Drug)
Treatment 2 in mCRPC: Poly ADP Ribose Polymerase (PARP) inhibitor
DNA-repair deficient patients will have an increased chance of receiving PARP inhibitors at study onset.
干预措施: Niraparib plus Abiraterone acetate plus Prednisone (Drug)
Treatment 3 in mCRPC: selective AKT Inhibitor
Patients with alterations in the PI3K pathway will have an increased chance of receiving the combination treatment with Capivasertib plus Docetaxel.
干预措施: Capivasertib plus Docetaxel (Drug)
Treatment 4 in mCRPC: Carboplatin
Only patients with DNA-repair deficiency will be treated with Carboplatin as second line treatment in the castration-resistant phase of ProBio.
干预措施: Carboplatin (Drug)
结局指标
主要结局
Progression free survival (PFS) in mCRPC
时间窗: Until progressive disease or 60 months from start of treatment, whatever occurs first.
Progression will be evaluated by the established international standards of the Prostate Cancer Working Group version 3 (PCWG3) and for soft tissue metastases (e.g. lung, liver and lymph nodes) according to the Response Evaluation Criteria in Solid Tumors (RECIST v. 1.1).
Progression free survival (PFS) in mHSPC
时间窗: From date of treatment start until the date of first documentation of progression, assessed up to 60 months
Time to development of castration-resistance, as defined by EAU guidelines (biochemical progression or radiologic progression)
次要结局
- Treatment response rate in mCRPC(4 months after treatment start)
- Number of Participants With Adverse Events as a Measure of Safety and Tolerability(From enrolment to completion of study (60 months))
- Treatment response rate in mHSPC(6 months after treatment start)
- Cost-effectiveness(From enrolment to completion of study (60 months))
- Overall survival (OS)(From enrolment to completion of study (60 months))
- Patient Reported Outcome Measures (PROM)(From enrolment to completion of study (60 months))
研究者
Henrik Grönberg
Professor of Cancer Epidemiology
Karolinska Institutet