A Phase III, Randomised, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of 10 mg ZD4054 in Combination with Docetaxel in comparison with Docetaxel in Patients with Metastatic Hormone-resistant Prostate Cancer

• Register: CTRI
• Last refreshed on: 4 May 2013
• Main ID: CTRI/2009/091/000193
• Date of registration: 12-06-2009
• Primary sponsor: AstraZeneca AB
• Public title: A Phase III, Randomised, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of 10 mg ZD4054 in Combination with Docetaxel in comparison with Docetaxel in Patients with Metastatic Hormone-resistant Prostate Cancer
• Scientific title: A Phase III, Randomised, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of 10 mg ZD4054 in Combination with Docetaxel in comparison with Docetaxel in Patients with Metastatic Hormone-resistant Prostate Cancer ENTHUSEM1C
• Date of first enrolment: 29-01-2008
• Target sample size: 1044
• Recruitment status: Completed
• URL: http://www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=448
• Study type: Interventional
• Study design: Randomized, Parallel Group, Placebo Controlled Trial; Method of generating randomization sequence:Stratified randomization Method of allocation concealment:Centralized Blinding and masking:Participant, Investigator and Outcome Assessor Blinded

Countries of recruitment

India

Contacts

• Name: Denzil Benjamin
• Affiliation: Assistant Director Mediacl Affairs

• Name: Muppavarapu Venkataraghuram
• Affiliation: Assistant Director Mediacl Affairs

Key inclusion & exclusion criteria

Inclusion criteria: For inclusion in the study patients must fulfil all of the following criteria:

1. Provision of informed consent

2. Male, aged 18 years or older. There is no upper limit for the age criteria.

3. Histological or cytological confirmation of adenocarcinoma of the prostate

4. Documented evidence of bone metastasis on 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 _?_ 5ng/mL in all other patients

6. Surgically castrated or continuously medically castrated with serum testosterone _?_2.4 nmol/L (70 ng/dL).

7. World Health Organisation (WHO) performance status 0 ? 1 (see Appendix E).

8. Life expectancy of 3 months or more.

For inclusion in the genetic component of the study, patients must fulfil the following criterion:

1. 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


Exclusion criteria: Any of the following is regarded as a criterion for exclusion from the study:
1. Radiotherapy to bone lesion or prostatic bed within 4 weeks of starting study treatment
2. 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)
3. Systemic radionuclide therapy (ie, strontium chloride Sr89, 186Relabeled HEDP, or 153Sm-EDTMP pentasodium) within 12 weeks of starting study treatment
4. Use of potent CYP450 inducers (such as phenytoin, rifampicin, carbamazepine, phenobarbitone, St John?s Wort) within 2 weeks of starting study treatment. Dexamethasone is a known inducer of CYP2D6 and CYP3A4 but is acceptable for this study when used as part of the standard docetaxel regime
5. Use of systemic retinoids within 2 weeks of starting study treatment
6. Have received investigational drug in another clinical study of anti-cancer therapy, within 4 weeks of starting study treatment
7. Prior therapy with endothelin receptor antagonists or family history of hypersensitivity to endothelin antagonists
8. Acute or evolving spinal cord compression or neurological symptoms or signs consistent with this. 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
9. Symptomatic peripheral neuropathy of CTCAE grade 2 or higher
10. Known or suspected central nervous system metastases.
11. History of past or current epilepsy, epilepsy syndrome, or other seizure disorder
12. 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
13. QT interval corrected for heart rate eg, by Bazett?s correction >470 msec
14. Previous history or presence of another malignancy within the preceding 5 years except treated squamous/basal cell carcinoma of the skin
15. 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
16. Absolute Neutrophil Count (ANC) <1.5 x 109/L (1,500/mm3); haemoglobin (Hb) &#61500;9 g/dL; platelet count <100 x 109/L (100,000/mm3). Concomitant use of erythropoietin or blood transfusions is allowed
17. Serum bilirubin >1.5 times the upper limit of normal (ULN). This will not apply to patients with confirmed 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
18. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2.5 times the ULN or 5 times the ULN in the presence of liver metastases
19. Creatinine clearance of <50 mL/minute, determined using the Cockcroft-Gault equation or by 24-hour creatinine clearance
20. 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

Age minimum:
Age maximum:
Gender:

Health Condition(s) or Problem(s) studied

Metastatic Hormone-resistant Prostate Cancer

Intervention(s)

Intervention1: ZD4054 PLUS DOCATAXEL: ZD4054 10 mg
Control Intervention1: Docetaxel: Docetaxel 75 mg/m2 administered intravenously (iv) over 1 hour on Day 1 of each 21-day cycle.

Primary Outcome(s)

The primary objective of this study is to determine the effect of ZD4054 in combination with docetaxel on overall survival compared with docetaxel; overall survival defined as time to death (from randomisation) from any causeTimepoint: Primary Analysis at 508 patients deaths

Secondary Outcome(s)

Assess the effect of ZD4054 in combination with docetaxel on progression free survival, on skeletal related events, on time to PSA progression, on time to pain progression, on pain response, on Health related Quality of Life, on PSA response.

Assess the safety & tolerability of ZD4054

Timepoint: Primary Analysis at 508 patients deaths

Secondary ID(s)

D4320C00033

NCT00617669

Source(s) of Monetary Support

AstraZeneca AB, 151 85 Södertälje, Sweden