|E.1 Medical condition or disease under investigation |
|E.1.1||Medical condition(s) being investigated || |
|E.1.1.1||Medical condition in easily understood language || |
|E.1.1.2||Therapeutic area ||Diseases [C] - Cancer [C04] |
|MedDRA Classification |
|E.1.2 Medical condition or disease under investigation |
|E.1.2||Version ||19.0 |
|E.1.2||Level ||PT |
|E.1.2||Classification code ||10062904 |
|E.1.2||Term ||Hormone-refractory prostate cancer |
|E.1.2||System Organ Class ||10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|E.1.3||Condition being studied is a rare disease || No |
|E.2 Objective of the trial |
|E.2.1||Main objective of the trial || |
|To determine the response rate to two cycles of platinum chemotherapy in patients with metastatic castration resistant prostate cancer (mCRPC) and a germline mutation in a DNA repair gene. |
|E.2.2||Secondary objectives of the trial || |
|•To assess progression-free and overall survival of patients with mCRPC and a DNA repair gene mutation after treatment with carboplatin. |
•To determine the rate of germline DNA repair gene mutations in patients with mCRPC.
|E.2.3||Trial contains a sub-study || No |
|E.3||Principal inclusion criteria || |
|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 LHRH analogues as per PCWG2 criteria.
4.Confirmed metastatic disease on conventional imaging methods such as CT, bone scan or PET imaging.
5.Current or previous treatment including docetaxel and/or enzalutamide/ abiraterone
6.Adequate renal function measured by calculated 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.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 study 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; AST and ALT ≤ 2.5x ULN in the presence of liver metastases.
4.Adequate renal function: creatinine clearance >40ml/min measured by EDTA clearance.
|E.4||Principal exclusion criteria|| |
|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 PARP inhibitor
5.Patients with a history of severe allergic to carboplatin or other platinum-containing compounds
6.Patients unfit for chemotherapy or those with ongoing neuropathy >grade 1 (sensory or motor) according to NCI CTCAE V4.02.
7.Known and documented hearing impairment
8.Other active malignancies or previous malignancies likely, in the PI’s opinion, to impact on management of mCRPC.
9.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).
10.Cerebrovascular disease (CVA or TIA) in the preceding 2 years to entry to Part 2 of study.
11.Presence of symptomatic brain metastases.
|E.5 End points |
|E.5.1||Primary end point(s)|| |
|Response rate to two cycles of platinum chemotherapy in patients with mCRPC and germline DNA repair gene mutations based on CT imaging using RECIST 1.1 criteria, and/or fall in PSA of >50%. |
|E.5.1.1||Timepoint(s) of evaluation of this end point|| |
|The primary endpoint will be evaluated approximately 6 weeks after the first dose of carboplatin chemotherapy (i.e. 3 weeks after the second dose of carboplatin). |
|E.5.2||Secondary end point(s)|| |
|• The incidence of germline mutations in DNA repair genes in a population of mCRPC cases. |
• Overall survival and progression free survival of patients with mCRPC and a DNA repair gene mutation treated with carboplatin.
• Cause specific survival from date of first diagnosis of prostate cancer in patients with germline DNA repair gene mutations
• Radiographic PFS
• Time to radiographic progression
• Time to PSA progression
• Duration and pattern of PSA response
|E.5.2.1||Timepoint(s) of evaluation of this end point|| |
|Imaging and blood tests for secondary endpoints will be carried out approximately every 9 weeks. Survival follow up after completion of treatment will be carried out every 3 months. |
|E.6 and E.7 Scope of the trial |
|E.6||Scope of the trial |
|E.6.1||Diagnosis|| No |
|E.6.2||Prophylaxis|| No |
|E.6.3||Therapy|| Yes |
|E.6.4||Safety|| No |
|E.6.5||Efficacy|| Yes |
|E.6.6||Pharmacokinetic|| No |
|E.6.7||Pharmacodynamic|| No |
|E.6.8||Bioequivalence|| No |
|E.6.9||Dose response|| No |
|E.6.10||Pharmacogenetic|| No |
|E.6.11||Pharmacogenomic|| No |
|E.6.12||Pharmacoeconomic|| No |
|E.6.13||Others|| No |
|E.7||Trial type and phase |
|E.7.1||Human pharmacology (Phase I)|| No |
|E.7.1.1||First administration to humans|| No |
|E.7.1.2||Bioequivalence study|| No |
|E.7.1.3||Other|| No |
|E.188.8.131.52||Other trial type description|| |
|E.7.2||Therapeutic exploratory (Phase II)|| Yes |
|E.7.3||Therapeutic confirmatory (Phase III)|| No |
|E.7.4||Therapeutic use (Phase IV)|| No |
|E.8 Design of the trial |
|E.8.1||Controlled|| No |
|E.8.1.1||Randomised|| No |
|E.8.1.2||Open|| No |
|E.8.1.3||Single blind|| No |
|E.8.1.4||Double blind || No |
|E.8.1.5||Parallel group|| No |
|E.8.1.6||Cross over || No |
|E.8.1.7||Other|| No |
|E.8.2|| Comparator of controlled trial |
|E.8.2.1||Other medicinal product(s)|| Information not present in EudraCT |
|E.8.2.2||Placebo || Information not present in EudraCT |
|E.8.2.3||Other|| Information not present in EudraCT |
|E.8.3|| The trial involves single site in the Member State concerned || Yes |
|E.8.4|| The trial involves multiple sites in the Member State concerned || No |
|E.8.4.1||Number of sites anticipated in Member State concerned||1 |
|E.8.5||The trial involves multiple Member States|| No |
|E.8.6 Trial involving sites outside the EEA |
|E.8.6.1||Trial being conducted both within and outside the EEA|| No |
|E.8.6.2||Trial being conducted completely outside of the EEA|| No |
|E.8.7||Trial has a data monitoring committee|| No |
|E.8.8|| Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial || |
|Date of last data capture, to gather data needed for evaluation of all endpoints |
|E.8.9 Initial estimate of the duration of the trial |
|E.8.9.1||In the Member State concerned years||3 |
|E.8.9.1||In the Member State concerned months||4 |
|E.8.9.1||In the Member State concerned days||1 |
|E.8.9.2||In all countries concerned by the trial years||3 |
|E.8.9.2||In all countries concerned by the trial months||4 |
|E.8.9.2||In all countries concerned by the trial days||1 |