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

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

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 (see inclusion/exclusion criteria further below).

Informed Consent

Participants will be given the latest ethically approved BARCODE 2 participant information sheet (PIS) for their consideration. Patients will only be asked to consent to the study after they have had sufficient time to consider the trial, and the opportunity to ask any further questions. Patients who have not had previous genetic testing will sign the part 1 consent form to undergo genetic profiling for a germline mutation in a DNA repair gene. Patients who are found to have a pathogenic mutation in part 1 or who are already known to carry a germline mutation must sign the part 2 consent form prior to undergoing part 2 study related procedures.

Patient Confidentiality

Patients will be asked to consent to their full name being collected at trial entry in addition to their date of birth, hospital number, postcode and National Health Service (NHS) number or equivalent to allow linkage with routinely collected NHS data and ensure accuracy in handling biological samples.

Investigators will ensure that all participants' personal identifier information is kept on a separate log.

Investigators will retain trial documents in strict confidence. Investigators will maintain the confidentiality of participants at all times and will not reproduce or disclose any information to third parties by which participants could be identified (without consent).

Data Protection

The study will comply with all applicable data protection laws.

Subject Withdrawal

Participants may discontinue from the trial at any time at their own request, or they may be discontinued from trial treatment at the discretion of the Principal Investigator (PI). Reasons for discontinuation will include:

• Clinical or radiological disease progression.
• Unacceptable toxicity (e.g. unresolving grade ≥2 neuropathy or neutropenia)
• Any other reason deemed appropriate by investigator. Increases in PSA will not be a criterion for treatment discontinuation in the absence of clinical or radiological progression. Participants who discontinue treatment should continue to be followed up until death.

Post-treatment Follow-up

Follow up data will be collected on all patients entering part 2 of the study who received carboplatin treatment on this trial until death, including cause of death. Survival data will be collected on all participants on the BARCODE 2 trial. Participants who discontinue treatment should continue to be followed up until death.

Discontinuation from Follow-up

If a patient withdraws from further follow-up, a trial deviation form should be submitted to Oncogenetics Team stating whether the patient has withdrawn consent for information to be sent to the Oncogenetics Team or whether they simply no longer wish to attend trial follow up visits. In the very rare event that a patient requests that their data is removed from the study entirely, the implications of this should be discussed with the patient first to ensure that this is their intent and, if confirmed, the Oncogenetics Team should be notified in writing. If this request is received after results have been published the course of action will be agreed between the Sponsor and Independent Data Monitoring and Steering Committee.

Trial Management

A Trial Management Group (TMG) will be set up and will include the Chief Investigator, the Trial Statistician and Trial Manager. Key study personnel will be invited to join the TMG as appropriate to ensure representation from a range of professional groups, including a PI from a Participant Identification Centre (PIC). Membership will include a lay/consumer representative who will receive support and training as deemed necessary. The TMG will meet at regular intervals, and at least annually. The TMG have operational responsibility for the conduct of the trial.

Independent Data Monitoring and Steering Committee (IDMSC)

A joint Independent Data Monitoring and Steering Committee (IDMSC) will be set up to oversee the safety of the trial participants, monitor the data produced by the trial, put these data into overall context and supervise the progress of the trial towards its interim and overall objectives.

Publication and Data Sharing Policy

The main trial results will be published in a peer-reviewed journal, on behalf of all collaborators. Anonymised data can be applied for via the Data Access Committee.