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

Uncategorized

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

Condition: Hormone Refractory Prostate Cancer

Intervention:

  • Drug: Carboplatin

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.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02955082

Sponsor: Institute of Cancer Research, United Kingdom

Primary Outcome Measures:

  • Measure: Radiographic Treatment Response
  • Time Frame: 6 weeks
  • Safety Issue:
  • Measure: Biochemical Treatment Response
  • Time Frame: 6 weeks
  • Safety Issue:

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:
  • 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:
  • 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:
  • Measure: Cause specific survival
  • Time Frame: This will be evaluated 3 months after end of study treatment
  • Safety Issue:
  • Measure: Radiographic progression free survival
  • Time Frame: This will be evaluated 3 months after end of study treatment
  • Safety Issue:
  • Measure: Time to radiographic progression
  • Time Frame: This will be evaluated 3 months after end of study treatment
  • Safety Issue:
  • Measure: PSA objective responses
  • Time Frame: This will be evaluated 3 months after end of study treatment
  • Safety Issue:

Estimated Enrollment: 450

Study Start Date: May 25, 2017

Phase: Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: Male

Inclusion Criteria:

  1. 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:
  2. Age ≥ 18 years.
  3. Histologically confirmed prostate adenocarcinoma. A copy of the original histology report from biopsy or surgery must be obtained.
  4. 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.
  5. Confirmed metastatic disease on conventional imaging methods such as computed tomography (CT), bone scan or positron emission tomography (PET) imaging.
  6. Current or previous treatment including docetaxel and/or enzalutamide/ abiraterone
  7. 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
  8. Adequate haematological function (haemoglobin ≥10g/dl, neutrophil count >1.5×109/L and platelets >100×109/L). This must be documented within 7 days of registration.
  9. World Health Organisation (WHO) performance status 0-2 as assessed and documented by study doctor.
  10. Life expectancy >12 weeks
  11. Patients with stable, treated brain metastases will be eligible providing informed consent can be given and that other sites of measurable disease are present
  12. 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:
  13. 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)
  14. Previous treatment with docetaxel and abiraterone or enzalutamide with documented disease progression prior to entry to part 2 (rising PSA and/or radiographic progression)
  15. 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.
  16. Adequate renal function: creatinine clearance >40ml/min measured by ethylenediaminetetraacetic acid (EDTA) clearance.

Exclusion Criteria:

  1. (for part 1 and 2):
  2. Critical organ metastases (e.g. spinal metastases with risk of cord compression) as documented on most recent imaging report.
  3. Patients with bleeding tumours.
  4. Previous treatment with a platinum chemotherapy drug for prostate cancer.
  5. Previous treatment with a poly adenosine diphosphate (ADP) ribose polymerase (PARP) inhibitor
  6. Patients with a history of severe allergic reaction to carboplatin or other platinum-containing compounds
  7. Exposure to yellow fever vaccine in the previous 6 months.
  8. 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.
  9. Known and documented hearing impairment
  10. Other active malignancies or previous malignancies likely, in the PI’s opinion, to impact on management of mCRPC.
  11. 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).
  12. Cerebrovascular disease (cerebrovascular accident (CVA) or transient ischaemic attach (TIA)) in the preceding 2 years to entry to Part 2 of study.
  13. Presence of symptomatic brain metastases.

Contact:

  • Elizabeth K Bancroft, PhD
  • +44 207 808 2136

Location:

  • Institute of Cancer Research and Royal Marsden Hospital
  • Sutton Surrey SM2 5PT United Kingdom

View trial on ClinicalTrials.gov

X