Prostate cancer Cancer Malignant neoplasm of prostate
Conditions
Interventions
Phase I
After a single dose pharmacokinetic (PK) study on day 7 of cycle 1 patients will commence combination treatment on day 1 of cycle 1 and will continue on treatment until confirmed disease progr
Sponsors
NHS Greater Glasgow and Clyde (UK)
Eligibility
Sex/Gender
Male
Age
18 Years to 110 Years
Inclusion criteria
Inclusion criteria: 1. Histologically proven adenocarcinoma of the prostate with documented metastases (where the metastatic lesions are confined to 1 or 2 lesions on a bone scan. These must be confirmed by a second modality (e.g. CT, MRI or biopsy). 2. Availability of archival tumour samples. Where patients are willing to undergo a biopsy as part of the study, these specimens may be used as an alternative where no archival specimen is available. 3. Proven disease progression since last change in therapy defined by at least one of the following: 3.1. Prostate-specific antigen (PSA) progression. This must be based on a series of at least three successively increasing readings each taken at least 7 days apart. The 3rd reading must be >= 2ng/ml. In the event where an intermediate reading is lower than a previous reading, then the patient will still be eligible (i.e. the three readings do not need to be consecutive). The first of the three readings must have been obtained after commencing the previous systemic therapy, or, in the case of androgen receptor antagonists, after discontinuing. 3.2. Radiographic progression since commencing last systemic anti-cancer therapy as defined by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 (Eisenhauer et al. 2009 Eur J Cancer. 4 5:2 2 8) for non-bone disease or the appearance of two or more new lesions on a bone scan. 4. Castrate levels of serum testosterone (= 10g/dL; platelets >= 150 x 109/L; neutrophils >=1.5 x109/L 9. Bilirubin < 1.5 x ULN; alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) < 2.5 x ULN 10. Serum potassium = LLN; Alb = 30 g/L 11. Serum creatinine < 1.5 x ULN or a calculated creatinine clearance = 60 mL/min 12. Able to swallow study drugs 13. Life expectancy of more than 3 months 14. Provision of written informed consent
Exclusion criteria
Exclusion criteria: 1. Prior cytotoxic chemotherapy for castration resistant prostate cancer (patients may have received previous or ongoing bisphosphonates, eg. zoledronate, or denosumab) 2. Prior ketoconazole, abiraterone, MDV3100 (enzalutamide), TAK-700 (orteronel) or other novel anti-hormonal therapies 3. Uncontrolled hypertension ( BP= 160 / 95 mmHg) 4. Significant heart disease as evident by myocardial infarction (MI) or arterial thrombotic events in past 6 months, severe unstable angina, or New York Heart Association class (NYHA) III or IV heart failure or class II to IV heart failure or cardic ejection fraction measurement of 325 mg po daily, clopidogrel, low molecular weight heparin, or dagibatran, etc.) prior to the start of study therapy are excluded. Patients may receive anticoagulant flushes for maintenance of indwelling catheters. 10. Patients with known bone marrow disorders which may interfere with bone marrow recovery (due to tumor involvement, fibrosis) (e.g. Concomitant myelodysplastic syndrome) 11. Patients who refuse blood products
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Radiological progression free survival [as per Prostate Cancer Working Group (2) (PCWG2)] Patients will have CT and bone scans at baseline then every 8 weeks for the first 24 weeks, thereafter every 12 weeks until progression is confirmed. Progression-free survival will be measured from the date of randomisation to the date of progression or date of death (any cause) for those who do not progress. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Prostate-specific antigen (PSA) response rate will be the proportion of patients achieving >50% drop in PSA for greater than 4 weeks. Patients will have PSA measured every 4 weeks. 2. Radiological response rate will be as per RECIST 1.1 for those patients with measurable disease at baseline. 3. For patients crossing over from placebo, PSA response rate will be the proportion of patients achieving >50% reduction in PSA from the point of cross over for > 4weeks 4. Biochemical and radiological PFS will be defined as the time from randomisation until the either PSA progression or radiological progression, (both as defined in PCWG2) or death (any cause) for patients who do not progress. 5. Pharmacokinetics (PK) of RO5503781 with and without abiraterone (phase I only) 6. Pharmacokinetics of abiraterone with and without RO5503781 (phase I only) 7. Pharmacokinetics of abiraterone in combination with RO5503781 Pharmacokinetics samples will be taken in the dose escalation phase of the study to explore the PK of both drugs alone and in combination. | — |
Countries
Scotland, United Kingdom
Contacts
Public ContactLorna Sweeting
Outcome results
None listed