An Open Phase II, Two-centre, 1-Arm Safety Study of Once-daily Orally Administered 10 mg ZD4054 in Prior Chemotherapy Treated Patients With Metastatic Hormone-resistant Prostate Cancer
Trial Snapshot
- Phase
- Phase 2
- Status
- Terminated
- Sponsor
- Enrollment
- 24
- Locations
- 1
- Primary Endpoint
- ECGs
Study Overview
Brief Summary
This is a prospective, open, one-arm, two-centre, Phase II clinical safety pilot-study. The trial is designed to gain initial safety and efficacy-related data on once-daily orally administered ZD4054 10 mg in prior chemotherapy treated patients with metastatic hormone-resistant prostate cancer.
Detailed Description
Study centres and number of patients planned This pilot study will be conducted in approximately 24 patients recruited from two hospital-based Danish centres: department of Urology K, Aarhus University Hospital, Skejby and department of Urologic Surgery D, Rigshospitalet. The recruitment of patients will be competitive among centres. 1-2 months before expected LSI it should be discussed if the target accrual should be expanded.
Study period Phase of development Estimated date of first patient enrolled August 1th 2009 II Estimated date of last patient completed July 31th 2012 Total study duration is approximately 36 months, which includes 12 months' recruitment, 36-month follow-up for safety and final survival analysis.
Objectives
The primary objective of this study is:
To assess the safety and tolerability profile of ZD4054 after treatment with chemotherapy
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 90 Years (Adult, Older Adult)
- Sex
- Male
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Provision of informed consent
- •Male, aged 18 years or older
- •Histological or cytological confirmation of adenocarcinoma of the prostate
- •Documented evidence of bone metastasis on bone scans.
- •Surgically castrated or continuously medically castrated with serum testosterone less than 2.4 nmol/L (70 ng/dL).
- •Previously (not inside 8 weeks) treated with at least two times 75 mg/m2 docetaxel.
- •Biochemical progression of prostate cancer after chemotherapy, documented while the patient is castrate:
- •o Biochemical progression is defined as at least 2 stepwise increases (≥1ng/mL) 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.
- •Life expectancy of 3 months or more.
Exclusion Criteria
- •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
- •Have received investigational drug in another clinical study of anticancer therapy, within 4 weeks of starting study treatment
- •Hypersensitivity to endothelin antagonists
- •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
- •History of past or current epilepsy, epilepsy syndrome, or other seizure disorder
- •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
- •QT interval corrected for heart rate e.g., by Bazett's correction >470 msec
- •In the opinion of the investigator, any evidence of severe or uncontrolled systemic disease (e.g., 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
- •Hemoglobin (Hb) <5 mmol/L. Concomitant use of erythropoietin or blood transfusions is allowed
- •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
- •Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2.5 times the ULN or 5 times the ULN in the presence of liver metastasis
- •Creatinine clearance of <50 mL/minute, determined using the Cockcroft-Gault equation or by 24-hour creatinine clearance
Arms & Interventions
ZD4054
The study had only one arm: intervention
Intervention: ZD4054 (Drug)
Outcomes
Primary Outcomes
ECGs
Time Frame: 2 years
Death from any cause
Time Frame: 2 years
Adverse events
Time Frame: 2 years
Physical Exam
Time Frame: 2 years
To assess the safety and tolerability profile of ZD4054 after treatment with chemotherapy
Time Frame: 2 years
Vital signs
Time Frame: 2 years
Laboratory data
Time Frame: 2 years
Secondary Outcomes
- To investigate the effect of ZD4054 on rate of rise of PSA(2 years)
- To investigate the effect of ZD4054 on prostate cancer related pain(2 years)
- To investigate the effect of ZD4054 on the plasma concentration of circulating tumour cells (CTC).(2 years)
Investigators
Michael Borre
Professor, DMSci, PhD
Aarhus University Hospital