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The BARCODE 2 Study - The Use of Genetic Profiling to Guide Prostate Cancer Treatment (BARCODE2)

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ClinicalTrials.gov Identifier: NCT02955082
Recruitment Status : Recruiting
First Posted : November 4, 2016
Last Update Posted : June 8, 2022
Sponsor:
Collaborators:
Royal Marsden NHS Foundation Trust
European Research Council
Imperial College Healthcare NHS Trust
Dartford and Gravesham NHS Foundation Trust
Mid and South Essex NHS Foundation Trust
Maidstone & Tunbridge Wells NHS Trust
East and North Hertfordshire NHS Trust
Royal Free Hampstead NHS Trust
Buckinghamshire Healthcare NHS Trust
Frimley Park Hospital NHS Trust
Barts & The London NHS Trust
Nottingham University Hospitals NHS Trust
Royal Surrey County Hospital NHS Foundation Trust
Yeovil District Hospital NHS Foundation Trust
Northampton General Hospital NHS Trust
Royal Devon and Exeter NHS Foundation Trust
Information provided by (Responsible Party):
Institute of Cancer Research, United Kingdom

Brief 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.

Condition or disease Intervention/treatment Phase
Hormone Refractory Prostate Cancer Drug: Carboplatin Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 450 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: The BARCODE 2 Study - The Use of Genetic Profiling to Guide Prostate Cancer Treatment
Actual Study Start Date : May 25, 2017
Estimated Primary Completion Date : September 30, 2024
Estimated Study Completion Date : September 30, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer
Drug Information available for: Carboplatin

Arm Intervention/treatment
Experimental: Carboplatin
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
Intravenous carboplatin infusion every 3 weeks.
Other Name: Paraplatin




Primary Outcome Measures :
  1. Radiographic Treatment Response [ Time Frame: 6 weeks ]
    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.

  2. Radiographic Treatment Response [ Time Frame: 9 weeks ]
    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.

  3. Biochemical Treatment Response [ Time Frame: 6 weeks ]
    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.


Secondary Outcome Measures :
  1. 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 ]
    Overall survival of patients with mCRPC and a DNA repair gene mutation treated with carboplatin.

  2. 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 ]
    Progression free survival of patients with mCRPC and a DNA repair gene mutation treated with carboplatin.

  3. Incidence of germline DNA repair gene mutations in a population of mCRPC cases [ Time Frame: Through study completion, up to 3 years ]
    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.

  4. Bone scan response [ Time Frame: Through study completion, up to 3 years ]
    Bone scan response (new lesion vs. no new lesions) at each time point in patients with bone-only metastatic disease.

  5. Cause specific survival [ Time Frame: This will be evaluated 3 months after end of study treatment ]
    Cause specific survival from date of first diagnosis of prostate cancer in patients with DNA repair gene mutations.

  6. Radiographic progression free survival [ Time Frame: This will be evaluated 3 months after end of study treatment ]
    Radiographic Progression free survival will be measured from the date of trial entry to the first occurrence of radiographic progression or death.

  7. Time to radiographic progression [ Time Frame: This will be evaluated 3 months after end of study treatment ]
    Time to radiographic progression will be measured from the date of trial entry to the first occurrence of radiographic progression.

  8. PSA objective responses [ Time Frame: This will be evaluated 3 months after end of study treatment ]
    PSA response and PSA progression are defined according to the consensus guidelines of the Prostate Cancer Working Group 3 (PCWG3).



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Eligible participants must be male at birth.
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02955082


Contacts
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Contact: Elizabeth K Bancroft, PhD +44 207 808 2136 elizabeth.bancroft@icr.ac.uk
Contact: Eva McGrowder, PhD +44 20 8722 4483 eva.mcgrowder@icr.ac.uk

Locations
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United Kingdom
Institute of Cancer Research and Royal Marsden Hospital Recruiting
Sutton, Surrey, United Kingdom, SM2 5PT
Contact: Rosalind A Eeles, FRCP FRFR    02086613642    rosalind.eeles@icr.ac.uk   
Principal Investigator: Rosalind A Eeles, FRCP FRCR         
Sponsors and Collaborators
Institute of Cancer Research, United Kingdom
Royal Marsden NHS Foundation Trust
European Research Council
Imperial College Healthcare NHS Trust
Dartford and Gravesham NHS Foundation Trust
Mid and South Essex NHS Foundation Trust
Maidstone & Tunbridge Wells NHS Trust
East and North Hertfordshire NHS Trust
Royal Free Hampstead NHS Trust
Buckinghamshire Healthcare NHS Trust
Frimley Park Hospital NHS Trust
Barts & The London NHS Trust
Nottingham University Hospitals NHS Trust
Royal Surrey County Hospital NHS Foundation Trust
Yeovil District Hospital NHS Foundation Trust
Northampton General Hospital NHS Trust
Royal Devon and Exeter NHS Foundation Trust
Investigators
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Principal Investigator: Rosalind A Eeles, FRCP, FRFR Institute of Cancer Research and Royal Marsden Hospital
Publications:
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Responsible Party: Institute of Cancer Research, United Kingdom
ClinicalTrials.gov Identifier: NCT02955082    
Other Study ID Numbers: CCR4520
First Posted: November 4, 2016    Key Record Dates
Last Update Posted: June 8, 2022
Last Verified: June 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Anonymised data can be applied for via the Data Access Committee.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Prostatic Diseases
Carboplatin
Antineoplastic Agents