The BARCODE 2 Study – The Use of Genetic Profiling to Guide Prostate Cancer Treatment

Phase 1

Conditions: Prostate Cancer
MedDRA version: 19.0Level: PTClassification code 10062904Term: Hormone-refractory prostate cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2016-000869-23-GB

Lead Sponsor: The Institute of Cancer Research

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: Male

Target Recruitment: Not specified

Inclusion Criteria

For Part 1 (genetic screening) of the study:
1.Age = 18 years.
2.Histologically confirmed prostate adenocarcinoma. A copy of the original histology report from biopsy or surgery must be obtained.
3.Castration-resistant disease defined as biochemical or radiological progression on/after treatment with orchidectomy or LHRH analogues as per PCWG2 criteria.
4.Confirmed metastatic disease on conventional imaging methods such as CT, bone scan or PET imaging.
5.Current or previous treatment including docetaxel and/or enzalutamide/ abiraterone
6.Adequate renal function measured by calculated GFR (Cockcroft-Gault) >30ml/min. This must be documented within 7 days of registration. If a patient had renal dysfunction that is expected to improve, they may be considered for part 1 of the study
7.Adequate haematological function (haemoglobin =10g/dl, neutrophil count >1.5x109/L and platelets >100x109/L). This must be documented within 7 days of registration.
8.WHO performance status 0-2 as assessed and documented by study doctor.
9.Life expectancy >12 weeks
10.Patients with stable, treated brain metastases will be eligible providing informed consent can be given and that other sites of measurable disease are present
11.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:
1.Confirmed pathogenic germline mutation in a DNA repair gene. (Patients with a known germline mutation will need to provide a report from the external laboratory where genetic testing was carried out)
2.Previous treatment with docetaxel and abiraterone or enzalutamide with documented disease progression prior to study entry to part 2 (rising PSA and/or radiographic progression)
3.Adequate liver function: Total bilirubin =1.5 x upper limit of normal (ULN) except for patients with known Gilbert’s syndrome; AST and ALT = 2.5x ULN in the presence of liver metastases.
4.Adequate renal function: creatinine clearance >40ml/min measured by EDTA clearance.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 40
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 14

Exclusion Criteria

Exclusion Criteria (for part 1 and 2)
1.Critical organ metastases (e.g. spinal metastases with risk of cord compression) as documented on most recent imaging report.
2.Patients with bleeding tumours.
3.Previous treatment with a platinum chemotherapy drug for prostate cancer.
4.Previous treatment with a PARP inhibitor
5.Patients with a history of severe allergic to carboplatin or other platinum-containing compounds
6.Patients unfit for chemotherapy or those with ongoing neuropathy >grade 1 (sensory or motor) according to NCI CTCAE V4.02.
7.Known and documented hearing impairment
8.Other active malignancies or previous malignancies likely, in the PI’s opinion, to impact on management of mCRPC.
9.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).
10.Cerebrovascular disease (CVA or TIA) in the preceding 2 years to entry to Part 2 of study.
11.Presence of symptomatic brain metastases.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To determine the response rate to two cycles of platinum chemotherapy in patients with metastatic castration resistant prostate cancer (mCRPC) and a germline mutation in a DNA repair gene. ;Secondary Objective: •To assess progression-free and overall survival of patients with mCRPC and a DNA repair gene mutation after treatment with carboplatin.<br>•To determine the rate of germline DNA repair gene mutations in patients with mCRPC.;Primary end point(s): Response rate to two cycles of platinum chemotherapy in patients with mCRPC and germline DNA repair gene mutations based on CT imaging using RECIST 1.1 criteria, and/or fall in PSA of >50%.;Timepoint(s) of evaluation of this end point: The primary endpoint will be evaluated approximately 6 weeks after the first dose of carboplatin chemotherapy (i.e. 3 weeks after the second dose of carboplatin).

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): • The incidence of germline mutations in DNA repair genes in a population of mCRPC cases.<br>• Overall survival and progression free survival of patients with mCRPC and a DNA repair gene mutation treated with carboplatin. <br>• Cause specific survival from date of first diagnosis of prostate cancer in patients with germline DNA repair gene mutations<br>• Radiographic PFS<br>• Time to radiographic progression<br>• Time to PSA progression<br>• Duration and pattern of PSA response;Timepoint(s) of evaluation of this end point: Imaging and blood tests for secondary endpoints will be carried out approximately every 9 weeks. Survival follow up after completion of treatment will be carried out every 3 months.