A Phase III Trial of ZD4054 (Zibotentan) (Endothelin A Antagonist) in Non-metastatic Hormone Resistant Prostate Cancer

Study Overview
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Brief Summary
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Enthuse M0 is a large phase III clinical trial studying the efficacy of ZD4054 (Zibotentan) in hormone resistant prostate cancer (HRPC). This clinical trial will test if the Endothelin A Receptor Antagonist ZD4054 (Zibotentan) can improve progression-free survival and overall survival against a background of existing prostate cancer treatments. ZD4054 (Zibotentan) is a new type of agent, which is thought to slow tumour growth and spread by blocking Endothelin receptor activity. This trial will look at the effects of ZD4054 (Zibotentan) in hormone resistant prostate cancer (HRPC) patients who have had rising PSA after surgical or medical castration but have no evidence of metastases. All patients participating in this clinical trial will receive existing prostate cancer treatments in addition to trial therapy. Half the patients will receive ZD4054 (Zibotentan) , and half the patients will receive placebo in addition to standard prostate cancer therapy. By participating in this trial there is a 50% chance that patients will receive an agent that may slow the progression of the tumour. No patients will be deprived of standard prostate cancer therapy.

Official Title
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A Phase III, Randomised, Placebo-controlled, Double-blind Study to Assess the Efficacy and Safety of Once-daily Orally Administered ZD4054 (Zibotentan) 10 mg in Non-metastatic Hormone-resistant Prostate Cancer Patients

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: ZD4054
* Drug: Palcebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who answer TRUE to the following criteria may be eligible to participate in this study. Confirmed diagnosis of prostate cancer (adenocarcinoma of the prostate) that has NOT spread to the other parts of the body (metastases). Patients with lymph node involvement may be eligible if specified criteria is met. Increasing Prostate Specific Antigen (PSA), collected within one year of enrollment Currently receiving treatment with surgical or medical castration Exclusion Criteria: Patients who answer TRUE to the following may NOT be eligible to participate in this study. Currently using opiate based pain killers for cancer related pain Previous treatment with chemotherapy (paclitaxel, docetaxel, and mitoxantrone). Prior targeted cancer therapies are permitted if received during a previous clinical trial Suffering from heart failure or had a myocardial infarction within last 6 months A history of epilepsy or seizures

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Matching Placebo | Drug: Palcebo<br>* Matching Plcebo oral tablet once daily<br>|
| Experimental: ZD4054<br>ZD4054 (Zibotentan) | Drug: ZD4054<br>* 10 mg once daily oral dose<br>* Other names: Zibotentan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Number of participants who have died at early analysis data cut off (DCO) | From date of randomization until date of death, assessed up to 33 months | 
| Progression Free Survival | Number of participants who have a progression event at the early analysis DCO, where progression is defined, using RECIST, as a measurable increase in the smallest dimension of any target or non-target lesion, or the appearance of new lesions, since baseline | Participants were followed up for progression every 4 weeks for the first 16 weeks then every 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Health Related Quality of Life |  | Participants were followed up every 4 weeks for the first 16 weeks then every 16 weeks | 
| Time to Prostate-specific Antigen (PSA) Progression |  | Participants were followed up every 4 weeks for the first 16 weeks then every 16 weeks | 
| Time to Symptomatic Progression |  | Participants were followed up every 4 weeks for the first 16 weeks then every 16 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hormone Resistant Prostate Cancer, Endothelin A Receptor Antagonist, Endothelin A, Endothelin A antagonist