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

NCT02955082 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: CCR4520
• Study Type: interventional
• Target: 305
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hormone Refractory Prostate Cancer

Outcome Measures

Primary Outcomes (3)

• Radiographic Treatment Response

  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.

  6 weeks

• Radiographic Treatment Response

  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.

  9 weeks

• Biochemical Treatment Response

  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.

  6 weeks

Secondary Outcomes (8)

• 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

• Bone scan response

  Through study completion, up to 3 years

• Cause specific survival

  This will be evaluated 3 months after end of study treatment

Study Arms (1)

Carboplatin

EXPERIMENTAL

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.

Drug: Carboplatin

Interventions

Carboplatin DRUG

Intravenous carboplatin infusion every 3 weeks.

Also known as: Paraplatin

Carboplatin

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Eligible participants must be male at birth.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

You may not qualify if:

• 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 V4.02.
• 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.

Sponsors & Collaborators

• Institute of Cancer Research, United Kingdom: lead
• Royal Marsden NHS Foundation Trust: collaborator
• European Research Council: collaborator
• Imperial College Healthcare NHS Trust: collaborator
• Dartford and Gravesham NHS Foundation Trust: collaborator
• Maidstone & Tunbridge Wells NHS Trust: collaborator
• East and North Hertfordshire NHS Trust: collaborator
• Royal Free Hampstead NHS Trust: collaborator
• Buckinghamshire Healthcare NHS Trust: collaborator
• Barts & The London NHS Trust: collaborator
• Nottingham University Hospitals NHS Trust: collaborator
• Yeovil District Hospital NHS Foundation Trust: collaborator
• Northampton General Hospital NHS Trust: collaborator

Study Sites (1)

Institute of Cancer Research and Royal Marsden Hospital

Sutton, Surrey, SM2 5PT, United Kingdom

Location

Related Publications (1)

• Scher HI, Morris MJ, Stadler WM, Higano C, Basch E, Fizazi K, Antonarakis ES, Beer TM, Carducci MA, Chi KN, Corn PG, de Bono JS, Dreicer R, George DJ, Heath EI, Hussain M, Kelly WK, Liu G, Logothetis C, Nanus D, Stein MN, Rathkopf DE, Slovin SF, Ryan CJ, Sartor O, Small EJ, Smith MR, Sternberg CN, Taplin ME, Wilding G, Nelson PS, Schwartz LH, Halabi S, Kantoff PW, Armstrong AJ; Prostate Cancer Clinical Trials Working Group 3. Trial Design and Objectives for Castration-Resistant Prostate Cancer: Updated Recommendations From the Prostate Cancer Clinical Trials Working Group 3. J Clin Oncol. 2016 Apr 20;34(12):1402-18. doi: 10.1200/JCO.2015.64.2702. Epub 2016 Feb 22.

  PMID: 26903579 BACKGROUND

MeSH Terms

Interventions

Carboplatin

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals

Study Officials

• Rosalind A Eeles, FRCP, FRFR

  Institute of Cancer Research and Royal Marsden Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 10, 2016
• First Posted: November 4, 2016
• Study Start: May 25, 2017
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2028
• Last Updated: February 4, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

GB (1)