A phase II, randomised, double-blind, parallel-group, placebo-controlled, multi-centre study to assess the efficacy and safety of once-daily orally administered ZD4054 15 mg and 10 mg doses in pain-free or mildly symptomatic patients with prostate cancer and bone metastases, who have rising serum prostate specific antigen (PSA) levels despite medical or surgical castration - EPOC
- Conditions
- Hormone-refractory prostate cancerMedDRA version: 6.1 Level: LLT Classification code 10062904
- Registration Number
- EUCTR2004-000344-24-GB
- Lead Sponsor
- AstraZeneca AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 260
1.Provision of written informed consent to participate in the study
2.Male, aged 18 years or older
3.Surgically castrated or continuously medically castrated with luteinising hormone-releasing hormone (LHRH) analogue
4.Patients with a serum testosterone inferior or equal to 1.73 nmol/L (50 ng/dL)
5.Histological or cytological confirmation of adenocarcinoma of the prostate.
6.Documented evidence of bone metastases, as assessed by bone scintigraphy performed according to the standard bone acquisition protocol developed specifically for this study.
-Patients must have disease involvement of less than 75% of the spine, 75% of the pelvis or 75% of the ribs in the anteroposterior (AP) or posteroanterior (PA) view.
-Patients with inferior or equal to 3 hot spots on the bone scan will require an additional scan to confirm metastatic disease, such as CT, magnetic resonance imaging (MRI) or X-ray, to be determined by the investigator.
7.Biochemical progression of prostate cancer, documented while the patient is castrate, by a rise in PSA that meets any one or more of the following criteria:
Biochemical progression criterion 1:
A second PSA value higher than a first PSA (reference) value. To be followed by a third PSA value higher than the second value.
-2 weeks minimum time interval between sampling
-All samples must have been taken within a 6-month period of randomisation to the study
-All PSA values must be superior or equal to 5 ng/mL
Biochemical progression criterion 2:
A second PSA value higher than a first PSA (reference) value. Followed by a third PSA value lower than the second, but with a fourth PSA value higher than the second.
-2 weeks minimum time interval between sampling
-All samples must have been taken within a 6-month period of randomisation to the study
-All PSA values must be superior or equal to 5 ng/mL
Biochemical progression criterion 3:
A PSA value greater than or equal to a doubling of a first PSA (reference) value. This must be confirmed by an additional PSA assessment which is also greater than or equal to a doubling of the reference value.
-2 weeks minimum time interval between sampling
-All samples must have been taken within a 6-month period of randomisation to the study
-All PSA values must be superior or equal to 5 ng/mL
Historical values may be used if they have been obtained from the same laboratory using the same PSA assay.
8.Creatinine clearance of >60 mL/minute, determined using the Cockcroft-Gault equation or by 24-hour creatinine clearance.
9.World Health Organisation (WHO) performance status 0 – 1 .
10. Life expectancy of 6 months or more
11.Clearly understand and be likely to comply with all study procedures
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
1.Current use (from the time that written informed consent is given) of any opiates listed in Appendix E of the protocol.
2.Prior radiotherapy to bone metastases within 4 weeks of randomisation to the study.
3.Prior cytotoxic chemotherapy for the treatment of their recurrent prostate cancer, such as estramustine, paclitaxel, docetaxel and mitoxantrone.
4.Corticosteroids, including hydrocortisone, for the treatment of their recurrent prostate cancer within 4 weeks of randomisation to the study. Please note that if taking corticosteroids for another reason, the treatment must be at a dose that is stable for a minimum of 12 weeks prior to randomisation to the study.
5.Antiandrogens, within 4 weeks of randomisation to the study for flutamide or within 6 weeks of randomisation to the study for bicalutamide and nilutamide. Continued elevation of their PSA, according to inclusion criterion number 7 (see Section 3.3.2 in the protocol), can be demonstrated during the washout times provided above.
6.Treatment with strontium-89, rhenium-186-HEDP and samarium-153-EDTMP for bone metastases, within 12 weeks of randomisation to the study.
7.Neurologic symptoms or signs consistent with acute or evolving spinal cord compression, confirmed with MRI. Stable, previously treated patients are allowed.
8.Stage II, III or IV cardiac failure, classified according to New York Heart Association (NYHA) classification.
9.QT interval corrected for heart rate (QTc) >470 msec.
10.In the opinion of the investigator, any evidence of severe or uncontrolled systemic disease, (eg, currently unstable or uncompensated respiratory, cardiac, hepatic or renal disease) or evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the patient to participate in the study.
11.Epilepsy or other seizure disorder, unless agreed upon by AstraZeneca.
12.Central nervous system metastases.
13.Total serum bilirubin greater than 1.5 times the upper limit of reference range (ULRR).
14.Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 1.5 times the ULRR.
15.Haemoglobin inferior or equal to 9 g/dL, neutrophils <1.5 x 109/L or platelets <75 x 109/L.
16.Prior therapy with endothelin receptor antagonists
17.Current therapy, or therapy within 2 weeks of randomisation to the study, with indinavir, itraconazole, ketoconazole and ritonavir (highly potent inhibitors of CYP450 3A4).
18.Current therapy, or therapy within 2 weeks of randomisation to the study, with carbamazepine, phenobarbitone, phenytoin, rifampicin and St John’s Wort (highly potent CYP450 inducers).
19.Use of systemic retinoids and herbal medicines or remedies (specifically, but not exclusively, to include saw palmetto and PC SPES), within 2 weeks of randomisation to the study.
20.Any serious condition which, in the opinion of the investigator, would present a risk to the patient participating in this study.
21.Have received investigational drug in another clinical study of anti-cancer therapy, within 4 weeks prior to consenting to this study. Please note restriction number 1 on bisphosphonates (see Section
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method