Using genetic profiling to guide treatment for prostate cancer

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

This study is testing if men with advanced prostate cancer who have certain genetic changes respond better to carboplatin treatment than those without these changes.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 450 (estimated)
• Ages: 18 Years and up
• Sex: Male
• Sponsor: Institute of Cancer Research, United Kingdom (other)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Sutton, Surrey)
• Trial ID: NCT02955082 on ClinicalTrials.gov

What this trial studies

The BARCODE 2 trial investigates how genetic changes in DNA repair genes influence the response to carboplatin treatment in men with metastatic castration-resistant prostate cancer (mCRPC). It consists of two parts: the first part involves genetic screening to identify patients with pathogenic mutations, while the second part offers carboplatin treatment to those identified as mutation carriers. The study aims to measure treatment response through prostate-specific antigen (PSA) levels and radiological assessments after two cycles of chemotherapy.

Who should consider this trial

Good fit: Ideal candidates include men aged 18 and older with metastatic castration-resistant prostate cancer who have progressed after prior treatments.

Not a fit: Patients who do not have a germline mutation in DNA repair genes or those with earlier-stage prostate cancer may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to more personalized and effective treatment options for patients with hormone refractory prostate cancer.

How similar studies have performed: Other studies have shown promise in using genetic profiling to tailor cancer treatments, suggesting that this approach may be beneficial.

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. 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. Androgen receptor-directed therapy (e.g., Enzalutamide, 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 androgen receptor-directed therapy (e.g., 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.

Where this trial is running

Sutton, Surrey

• Institute of Cancer Research and Royal Marsden Hospital — Sutton, Surrey, United Kingdom (RECRUITING)

Study contacts

• Principal investigator: Rosalind A Eeles, FRCP, FRFR — Institute of Cancer Research and Royal Marsden Hospital
• Study coordinator: Elizabeth K Bancroft, PhD

Conditions: Hormone Refractory Prostate Cancer