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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02955082
Recruitment Status : Recruiting
First Posted : November 4, 2016
Last Update Posted : February 17, 2020
Sponsor:
Collaborators:
Royal Marsden NHS Foundation Trust
European Research Council
Colchester Hospital University NHS Foundation Trust
Imperial College Healthcare NHS Trust
Dartford and Gravesham NHS Foundation Trust
Medway NHS Foundation Trust
Southend University Hospital Foundation NHS Trust
Great Ormond Street Hospital for Children NHS Foundation Trust
Maidstone & Tunbridge Wells NHS Trust
East and North Hertfordshire NHS Trust
Royal Free Hampstead NHS Trust
The Whittington Hospital NHS Trust
Luton and Dunstable Hospital NHS Foundation Trust
Buckinghamshire Healthcare NHS Trust
Chelsea and Westminster NHS Foundation Trust
Frimley Park Hospital NHS Trust
North Middlesex University Hospital NHS Trust
Whipps Cross University NHS Trust
Barts & The London NHS Trust
Heatherwood and Wexham Park Hospitals 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 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.

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, 2020
Estimated Study Completion Date : April 25, 2022

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

  2. 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. 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.

  5. 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.

  6. 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.

  7. 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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
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. 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.

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
Colchester Hospital University NHS Foundation Trust
Imperial College Healthcare NHS Trust
Dartford and Gravesham NHS Foundation Trust
Medway NHS Foundation Trust
Southend University Hospital Foundation NHS Trust
Great Ormond Street Hospital for Children NHS Foundation Trust
Maidstone & Tunbridge Wells NHS Trust
East and North Hertfordshire NHS Trust
Royal Free Hampstead NHS Trust
The Whittington Hospital NHS Trust
Luton and Dunstable Hospital NHS Foundation Trust
Buckinghamshire Healthcare NHS Trust
Chelsea and Westminster NHS Foundation Trust
Frimley Park Hospital NHS Trust
North Middlesex University Hospital NHS Trust
Whipps Cross University NHS Trust
Barts & The London NHS Trust
Heatherwood and Wexham Park Hospitals 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: February 17, 2020
Last Verified: February 2020
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