Clinical Trials /

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

NCT02955082

Description:

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 study is formed of two parts that aim to investigate how having genetic changes in DNA repair genes can affect response to treatment. In part 1 of the study, the investigators will invite men with metastatic castration resistant prostate cancer (mCRPC) who have not had genetic testing before to join the study by initially undergoing genetic screening within the study. 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. 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 the 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.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: The BARCODE 2 Study - The Use of Genetic Profiling to Guide Prostate Cancer Treatment
  • Official Title: The BARCODE 2 Study - The Use of Genetic Profiling to Guide Prostate Cancer Treatment

Clinical Trial IDs

  • ORG STUDY ID: CCR4520
  • NCT ID: NCT02955082

Conditions

  • Hormone Refractory Prostate Cancer

Interventions

DrugSynonymsArms
CarboplatinParaplatinCarboplatin

Purpose

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 study is formed of two parts that aim to investigate how having genetic changes in DNA repair genes can affect response to treatment. In part 1 of the study, the investigators will invite men with metastatic castration resistant prostate cancer (mCRPC) who have not had genetic testing before to join the study by initially undergoing genetic screening within the study. 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. 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 the 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.

Detailed Description

      Purpose and Design

      BARCODE 2 is a single arm, single site phase II study 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,
      enrolled patients' DNA repair gene mutation carrier status 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 and abiraterone or enzalutamide may
      be assessed for eligibility for study entry.

      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.

      Informed Consent

      Participants will be given the current ethically approved BARCODE 2 patient information sheet
      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 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 until death,
      including cause of death. 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). The TMG will meet at regular intervals, and at
      least annually.

      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.
    

Trial Arms

NameTypeDescriptionInterventions
CarboplatinExperimentalPatients 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.
  • Carboplatin

Eligibility 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. 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 Luteinizing hormone-releasing hormone (LHRH)
             analogues as per PCWG3 criteria.

          4. Confirmed metastatic disease on conventional imaging methods such as computed
             tomography (CT), bone scan or positron emission tomography (PET) imaging.

          5. Current or previous treatment including docetaxel and/or enzalutamide/ abiraterone

          6. Adequate renal function measured by calculated glomerular filtration rate (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. World Health Organisation (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 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; aspartate aminotransferase (AST) and alanine
             aminotransferase (ALT) ≤ 2.5x ULN in the presence of liver metastases.

          4. Adequate renal function: creatinine clearance >40ml/min measured by
             ethylenediaminetetraacetic acid (EDTA) clearance.

        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 poly adenosine diphosphate (ADP) ribose polymerase (PARP)
             inhibitor

          5. Patients 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. Patients unfit for chemotherapy or those with ongoing neuropathy >grade 1 (sensory or
             motor) according to the National Cancer Institute (NCI) common terminology criteria
             for adverse events (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 (New York Heart Association (NYHA) classes II-IV).

         11. Cerebrovascular disease (cerebrovascular accident (CVA) or transient ischaemic attach
             (TIA)) in the preceding 2 years to entry to Part 2 of study.

         12. Presence of symptomatic brain metastases.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Radiographic Treatment Response
Time Frame:6 weeks
Safety Issue:
Description: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

Secondary Outcome Measures

Measure:Overall survival of men with mCRPC and germline DNA repair gene mutations
Time Frame:This will be evaluated 3 months after end of study treatment
Safety Issue:
Description:Overall survival of patients with mCRPC and a DNA repair gene mutation treated with carboplatin.
Measure:Progression-free survival of men with mCRPC and germline DNA repair gene mutations
Time Frame:This will be evaluated 3 months after end of study treatment
Safety Issue:
Description:Progression free survival of patients with mCRPC and a DNA repair gene mutation treated with carboplatin.
Measure:Incidence of germline DNA repair gene mutations in a population of mCRPC cases
Time Frame:Through study completion, up to 3 years
Safety Issue:
Description:Incidence of germline DNA repair gene mutations will be calculated from the rate of pathogenic mutations observed in the group of men who undergo genetic profiling within part 1 of the study.
Measure:Cause specific survival
Time Frame:This will be evaluated 3 months after end of study treatment
Safety Issue:
Description:Cause specific survival from date of first diagnosis of prostate cancer in patients with DNA repair gene mutations.
Measure:Radiographic progression free survival
Time Frame:This will be evaluated 3 months after end of study treatment
Safety Issue:
Description:Radiographic Progression free survival will be measured from the date of trial entry to the first occurrence of radiographic progression or death.
Measure:Time to radiographic progression
Time Frame:This will be evaluated 3 months after end of study treatment
Safety Issue:
Description:Time to radiographic progression will be measured from the date of trial entry to the first occurrence of radiographic progression.
Measure:PSA objective responses
Time Frame:This will be evaluated 3 months after end of study treatment
Safety Issue:
Description:PSA response and PSA progression are defined according to the consensus guidelines of the Prostate Cancer Working Group 3 (PCWG3).

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Institute of Cancer Research, United Kingdom

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