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

• Status: Recruiting
• Trial end date: 2024-09-30
• Target enrollment: 0
• Participant gender: Male

Summary

Prostate cancer (PrCa) is one of the commonest cancer in men in the Western world, with over 40,000 new cases diagnosed each year in the United Kingdom (UK). 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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Institute of Cancer Research, United Kingdom
• Collaborators: Barts & The London NHS Trust; Buckinghamshire Healthcare NHS Trust; Chelsea and Westminster NHS Foundation Trust; Colchester Hospital University NHS Foundation Trust; Dartford and Gravesham NHS Foundation Trust; East and North Hertfordshire NHS Trust; European Research Council; Frimley Park Hospital NHS Trust; Great Ormond Street Hospital for Children NHS Foundation Trust; Heatherwood and Wexham Park Hospitals NHS Foundation Trust; Imperial College Healthcare NHS Trust; Luton and Dunstable Hospital NHS Foundation Trust; Maidstone & Tunbridge Wells NHS Trust; Medway NHS Foundation Trust; Mid and South Essex NHS Foundation Trust; North Middlesex University Hospital NHS Trust; Northampton General Hospital NHS Trust; Nottingham University Hospitals NHS Trust; Royal Devon and Exeter NHS Foundation Trust; Royal Free Hampstead NHS Trust; Royal Marsden NHS Foundation Trust; Royal Surrey County Hospital NHS Foundation Trust; Southend University Hospital Foundation NHS Trust; The Whittington Hospital NHS Trust; Whipps Cross University NHS Trust; Yeovil District Hospital NHS Foundation Trust
• Treatments: Carboplatin

Criteria

Inclusion Criteria:

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:

1. Age ≥ 18 years.

2. 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.

3. Castration-resistant disease defined as biochemical or radiological progression on/after treatment with orchidectomy or LHRH analogues as per PCWG3 criteria.

4. Confirmed metastatic disease on conventional imaging methods such as CT, bone scan or PET imaging.

5. Current or previous treatment includes at least one of the following:

1. Docetaxel (either in hormone sensitive or resistant setting; Patients who have completed treatment with or are currently undergoing Cabazitaxel chemotherapy are also eligible)

2. Enzalutamide

3. Abiraterone

6. 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.

7. Adequate haematological function to allow study entry in line with local hospital practice or at the investigator's discretion.

8. WHO performance status 0-2 as assessed and documented by study doctor.

9. Life expectancy >12 weeks

10. Participants 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. (Participants 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 entry to part 2 (rising PSA and/or radiographic progression). Patients previously treated with cabazitaxel and who have documented disease progression are also eligible.

3. Adequate haematological function: Haemoglobin (Hb) ≥8.0g/dL, neutrophil count ≥1.5x109/L and platelets ≥100x109/L.

4. 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.

5. 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).

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. Participants with bleeding tumours.

3. Previous treatment with a platinum chemotherapy drug for prostate cancer.

4. Previous treatment with a PARP inhibitor

5. Participants with a history of severe allergic reaction to carboplatin or other platinum-containing compounds

6. Exposure to yellow fever vaccine in the previous 6 months.

7. Participants unfit for chemotherapy or those with ongoing neuropathy >grade 1 (sensory or motor) according to NCI CTCAE V4.02.

8. Known and documented hearing impairment

9. Other active malignancies or previous malignancies likely, in the PI's opinion, to impact on management of mCRPC.

10. 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).

11. Cerebrovascular disease (CVA or TIA) in the preceding 2 years to entry to Part 2 of study.

12. Presence of symptomatic brain metastases.