A Phase III, Randomised, Double-blind Study to Assess the Efficacy and Safety of 10 mg ZD4054 versus Placebo in Patients with Hormone-resistant Prostate Cancer and Bone Metastasis who are Pain Free or Mildly Symptomatic - D4320C00014

• Conditions: hormone-resistant prostate cancer; MedDRA version: 6.1Level: LLTClassification code 10062904Term: <Manually entered code. Term in E.1.1>

• Registration Number: EUCTR2007-003227-20-HU
• Lead Sponsor: AstraZeneca AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-11-09
• Last Update Posted: 1 May 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Male
• Target Recruitment: 580

Inclusion Criteria

1.Provision of informed consent
2.Male, aged 18 years or older
3.Histological or cytological confirmation of adenocarcinoma of the prostate
4.Documented evidence of bone metastasis on radionuclide bone scan. Patients must have disease involvement <75% of the spine, pelvis and ribs in the anteroposterior (AP) or posteroanterior (PA) view. Patients with =3 lesions seen on bone scan will require a CT scan, MRI or x-ray to confirm
5.Biochemical progression of prostate cancer, documented while the patient is castrate:
-Biochemical progression is defined as at least 2 stepwise increases in PSA over a period of =1 month (values do not need to be consecutive but 2 values that have increased since the previous highest value are required) with at least 14 days between each measurement irrespective of assay or laboratory
-Historical values may be used
-The last PSA must be an increase of =50 % of the first PSA value of the 3 values or an absolute increase of =10 ng/mL over the initial PSA
-The final PSA value must be =1.2 ng/mL in patients who have had a radical prostatectomy and =5 ng/mL in all other patients
6.Asymptomatic or mild pain from prostate cancer, defined as a score of =2 in the worst pain item of the BPI
7.Surgically castrated or continuously medically castrated with serum testosterone =2.4 nmol/L (70 ng/dL)
8.World Health Organisation (WHO) performance status 0 - 1
9.Life expectancy of 6 months or more.
For inclusion in the genetic component of the study, patients must fulfil the following criterion:
10.Provision of informed consent for genetic research.
If a patient declines to participate in the genetic research, there will be no penalty or loss of benefit to the patient. The patient will not be excluded from other aspects of the study described in this Clinical Study Protocol, so long as they consent to participate
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

Exclusion Criteria

1.Radiotherapy to bone lesion or prostatic bed within 4 weeks of starting study treatment
2.Current use (from the time that written informed consent is given) of any opiates, with the exception of opiates taken PRN for pain not directly related to prostate cancer
3.Prior cytotoxic chemotherapy (such as paclitaxel, docetaxel and mitoxantrone) for the treatment of recurrent prostate cancer (prior estramustine therapy is allowed), as well as other targeted cancer therapies (such as EGF, EGFR, VEGF and VEGFR)
4.Systemic radionuclide therapy (ie, strontium chloride Sr89, 186Relabeled HEDP, or 153Sm-EDTMP pentasodium) within 12 weeks of starting study treatment
5.Use of potent CYP450 inducers (such as phenytoin, rifampicin, carbamazepine, phenobarbitone and St John’s Wort) within 2 weeks of starting study treatment. Dexamethasone will be allowed if the investigator feels it is necessary but is encouraged to use a different form of steroid treatment wherever possible
6.Use of systemic retinoids within 2 weeks of starting study treatment
7.Have received investigational drug in another clinical study of anticancer therapy, within 4 weeks of starting study treatment
8.Prior therapy with endothelin receptor antagonists or family history of hypersensitivity to endothelin antagonists
9.Neurological symptoms or signs consistent with acute or evolving spinal cord compression. If a patient has neurologic symptoms, an MRI must be performed that demonstrates no impending or actual spinal cord compression. Stable, previously treated patients are allowed
10.Symptomatic peripheral neuropathy of CTCAE grade 2 or higher
11.Known or suspected central nervous system metastases
12.History of past or current epilepsy, epilepsy syndrome, or other seizure disorder
13.Stage II, III or IV cardiac failure (classified according to New York Heart Association (NYHA) classification) or myocardial infarction within 6 months prior to study entry
14.QT interval corrected for heart rate eg, by Bazett’s correction >470 msec
15.Previous history or presence of another malignancy, other than prostate cancer or treated squamous/basal cell carcinoma of the skin, within the last 5 years
16.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
17.Hemoglobin (Hb) <9 g/dL. Concomitant use of erythropoietin or blood transfusions is allowed
18.Serum bilirubin >1.5 times the upper limit of normal (ULN). This will not apply to patients with Gilbert’s syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of evidence of haemolysis or hepatic pathology), who will be allowed in consultation with their physician
19.Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2.5 times the ULN or 5 times the ULN in the presence of liver metastasis
20.Creatinine clearance of <50 mL/minute, determined using the Cockcroft-Gault equation or by 24-hour creatinine clearance
21.Patients who discontinue after randomisation cannot be re-enrolled. Patients who fail to meet the inclusion/exclusion criteria may be reconsidered once for participation in the study. Patients who are re-enrolled must be re-consented and will be assigned a new enrolment number
22.Involvement

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified