The BARCODE 2 Study - The Use of Genetic Profiling to Guide Prostate Cancer Treatment
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 305
- 试验地点
- 1
- 主要终点
- Biochemical Treatment Response
研究概览
简要总结
Prostate cancer (PrCa) is one of the commonest cancer in men in the Western world. In the United Kingdom (UK), there were over 52,000 new cases diagnosed in 2016-2018 and a lifetime risk of 1 in 8. Research studies have identified several genetic changes that are thought to increase the risk of developing prostate cancer. Some of these genetic changes occur in deoxyribonucleic acid (DNA) repair genes. The BARCODE 2 trial is formed of two parts that aim to investigate how having genetic changes in DNA repair genes can affect response to carboplatin treatment in patients with metastatic castration resistant prostate cancer (mCRPC). In part 1 of the study, the investigators will invite men with mCRPC who have not had genetic testing before to join the study by initially undergoing genetic screening within the study. The DNA repair gene mutation carrier status of enrolled patients will be assessed using a gene panel. If a pathogenic mutation is confirmed in one of these genes, patients will be given the option to proceed to part 2 of the study. In part 2 of the study, men with mCRPC who are known to be carriers of a mutation in DNA repair gene(s) will be assessed for eligibility for treatment on the study with carboplatin chemotherapy. The aim of the study will be to determine how patients with mCRPC and a germline mutation in a DNA repair gene(s) respond to platinum chemotherapy. This study will help researchers to investigate platinum sensitivity of prostate tumours that have developed due to a germline mutation in a DNA repair gene. This study will provide data to use in a larger clinical trial of platinum chemotherapy based on patients' germline genetic signature and/or tumour genetic profile.
详细描述
Purpose and Design
BARCODE 2 is a single arm, single site phase II trial with the aim to determine the response rate to two cycles of platinum chemotherapy in patients with mCRPC and a germline mutation in a DNA repair gene. Response will be measured with prostate specific antigen (PSA) levels and radiological assessment. The study will be divided into two parts. In part 1 of the study, the DNA repair gene mutation carrier status of enrolled patients will be assessed using a gene panel. Men who are found to carry a pathogenic mutation or are already known to carry a germline mutation can enrol in part 2 of the study and be offered treatment with carboplatin.
Eligibility and Recruitment
Patients with mCRPC which has progressed after docetaxel chemotherapy and androgen receptor-directed therapy (e.g., abiraterone or enzalutamide) may be assessed for eligibility for study entry. Patients who have completed treatment with or are currently undergoing cabazitaxel chemotherapy are also eligible.
Inclusion Criteria
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •All study participants will be assessed according to the part 1 and/ or part 2 inclusion criteria depending on which part of the study they enter initially.
- •For Part 1 (genetic screening) of the study:
- •Age ≥ 18 years.
- •Recorded diagnosis of prostate cancer with or without histological confirmation. Patients who have not previously undergone a prostate (or metastatic) biopsy but are confirmed to have a raised PSA (>80ng/ml at any time), metastatic disease on imaging and have undergone treatment for mCRPC are eligible.
- •Castration-resistant disease defined as biochemical or radiological progression on/after treatment with orchidectomy or LHRH analogues as per PCWG3 criteria.
- •Confirmed metastatic disease on conventional imaging methods such as CT, bone scan or PET imaging.
- •Current or previous treatment includes at least one of the following:
- •Docetaxel (either in hormone sensitive or resistant setting; Patients who have completed treatment with or are currently undergoing Cabazitaxel chemotherapy are also eligible)
- •Androgen receptor-directed therapy (e.g., Enzalutamide, Abiraterone)
- •Adequate renal function measured by calculated GFR (Cockcroft-Gault) >30ml/min. If a participant had renal dysfunction that is expected to improve, they may be considered for part 1 of the study.
- •Adequate haematological function to allow study entry in line with local hospital practice or at the investigator's discretion.
- •WHO performance status 0-2 as assessed and documented by study doctor.
- •Life expectancy >12 weeks
- •Participants with stable, treated brain metastases will be eligible providing informed consent can be given and that other sites of measurable disease are present
- •The subject is capable of understanding and complying with the protocol requirements and has signed the BARCODE 2 informed consent form.
- •In addition to the above, for Part 2 of the study:
- •Confirmed pathogenic germline mutation in a DNA repair gene. (Participants with a known germline mutation will need to provide a report from the external laboratory where genetic testing was carried out)
- •Previous treatment with docetaxel and androgen receptor-directed therapy (e.g., abiraterone or enzalutamide) with documented disease progression prior to entry to part 2 (rising PSA and/or radiographic progression). Patients previously treated with cabazitaxel and who have documented disease progression are also eligible.
- •Adequate haematological function: Haemoglobin (Hb) ≥8.0g/dL, neutrophil count ≥1.5x109/L and platelets ≥100x109/L.
- •Adequate liver function: Total bilirubin ≤1.5 x upper limit of normal (ULN) except for participants with known Gilbert's syndrome; AST and ALT ≤ 2.5x ULN in the presence of liver metastases.
- •Adequate renal function: creatinine clearance >30ml/min measured by a glomerular filtration rate (GFR) clearance test. If a measured GFR test is not available, then calculated GFR is acceptable (measured GFR must be carried out by cycle 2 of carboplatin).
排除标准
- •(for part 1 and 2):
- •Critical organ metastases (e.g. spinal metastases with risk of cord compression) as documented on most recent imaging report.
- •Participants with bleeding tumours.
- •Previous treatment with a platinum chemotherapy drug for prostate cancer.
- •Previous treatment with a PARP inhibitor
- •Participants with a history of severe allergic reaction to carboplatin or other platinum-containing compounds
- •Exposure to yellow fever vaccine in the previous 6 months.
- •Participants unfit for chemotherapy or those with ongoing neuropathy >grade 1 (sensory or motor) according to NCI CTCAE V4.
- •Known and documented hearing impairment
- •Other active malignancies or previous malignancies likely, in the PI's opinion, to impact on management of mCRPC.
- •Significant documented cardiovascular disease: severe/unstable angina, myocardial infarction less than 6 months prior to trial entry, arterial thrombotic events less than 6 months prior to trial entry, clinically significant cardiac failure requiring treatment (NYHA II-IV).
- •Cerebrovascular disease (CVA or TIA) in the preceding 2 years to entry to Part 2 of study.
- •Presence of symptomatic brain metastases.
研究组 & 干预措施
Carboplatin
Patients with a germline DNA repair gene mutation identified in part 1 of the study, or who are already known to have a germline mutation will undergo assessment for inclusion in part 2 of the study to receive Carboplatin treatment.
干预措施: Carboplatin (Drug)
结局指标
主要结局
Biochemical Treatment Response
时间窗: 6 weeks
Reduction of more than 50% in PSA levels in response to two cycles of platinum chemotherapy in patients with mCRPC and germline DNA repair gene mutations.
Radiographic Treatment Response
时间窗: 9 weeks
Response rate to three cycles of platinum chemotherapy in patients with mCRPC and germline DNA repair gene mutations via bone scan assessment. In participants with bone only metastatic disease, response will be recorded as having 'new lesions' or 'no new lesions' (as per PCWG3 guidance). Participants with no new bone lesions will be deemed as having stable disease. These participants can respond by PSA as defined below.
Radiographic Treatment Response
时间窗: 6 weeks
Response rate to two cycles of platinum chemotherapy in patients with mCRPC and germline DNA repair gene mutations using the modified response evaluation criteria in solid tumours (RECIST) 1.1 criteria. In participants with bone only metastatic disease, response will be recorded as having 'new lesions' or 'no new lesions' (as per the Prostate Cancer Working Group 3 (PCWG3) guidance). Participants with no new bone lesions will be deemed as having stable disease. These participants can respond by PSA as defined below.
次要结局
- Overall survival of men with mCRPC and germline DNA repair gene mutations(This will be evaluated 3 months after end of study treatment)
- Progression-free survival of men with mCRPC and germline DNA repair gene mutations(This will be evaluated 3 months after end of study treatment)
- Incidence of germline DNA repair gene mutations in a population of mCRPC cases(Through study completion, up to 3 years)
- Radiographic progression free survival(This will be evaluated 3 months after end of study treatment)
- Time to radiographic progression(This will be evaluated 3 months after end of study treatment)
- Bone scan response(Through study completion, up to 3 years)
- PSA objective responses(This will be evaluated 3 months after end of study treatment)
- Cause specific survival(This will be evaluated 3 months after end of study treatment)