Clinical trial NCT00659438: Efficacy and Safety of Zactima™ in Patients With Castration-refractory Metastatic Prostate Cancer
Official title: A Randomized, Double-blind Phase II Trial to Assess the Efficacy and Safety of Bicalutamide (Casodex® ) Associated to ZD6474 (Zactima™ ) or to Placebo in Patients With Castration-refractory Metastatic Prostate Cancer Without Any Clinical Symptom Related to Disease Progression
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Prostate Cancer
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2008-04-16
Enrollment: 95
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This randomized, double-blind phase II trial is to assess the efficacy and safety of bicalutamide (Casodex® ) associated to ZD6474 (Zactima™ ) or to placebo in patients with castration-refractory metastatic prostate cancer without any clinical symptom related to disease progression. The study is blinded, and subjects will be randomised (1:1 ratio) to either ZD6474 300 mg or placebo. The blinded design ensures robust, unbiased data collection and assessment. Placebo control is necessary to ensure a robust assessment of PSA PFS, and is acceptable in this subject population where all subjects will also received bicalutamide 150 mg o.d. Subjects will continue study treatment until they reach objective biological disease progression or unacceptable toxicity or withdrawal of consent or until end of trial (which event occurs first). The end of study is fixed 12 months after the last randomised patient's first dose of study treatment.


Eligibility criteria: Inclusion Criteria:

* Males presented with a confirmed histological diagnosis of adenocarcinoma of the prostate with evidence of metastases (including bone, lymph nodes, or other site) radiologically or histologically documented and despite a serum testosterone ≤1.73 nmol/L (50 ng/dL) proving castration, evidence of biochemical progression of prostate cancer, documented by a rise in PSA .

Exclusion Criteria:

* Radiotherapy or surgery or antiandrogens (except LHRH analogue) or bilateral orchiectomy within the 30 days preceding Visit 1. Incompletely healed surgical incision.
* Concomitant anticancer therapy other than surgical castration or continuous medical castration.
* Biology restriction.
* Clinical significant cardiovascular event or presence of cardiac disease that in the opinion of the Investigator increases the risk of ventricular arrhythmia.
* History of arrhythmia which is symptomatic or requires treatment (CTCAE grade 3), symptomatic despite treatment, or asymptomatic sustained ventricular tachycardia. Subjects with atrial fibrillation controlled on medication are permitted.
* Hypertension not controlled by medical therapy
* ECG /QTc prolongation
* Presence of left bundle branch block (LBBB).

Primary outcomes:
measure: Prostate Specific Antigen (PSA) Progression Free Rate at 4 Months
timeFrame: 4 months
Secondary outcomes:
measure: Progression Free Survival (PFS) at 4 Months (Instead of Time to PSA Progression)
timeFrame: 4 months
measure: Progression Free Survival (PFS) at 4 Months (Instead of Time to Onset of Cancer-related Symptoms)
timeFrame: 4 months
measure: PSA Response Rate
timeFrame: 4 months
measure: Overall Survival (OS)
timeFrame: End of study (July 2011)
measure: Progression Rate From the Radionuclide Bone Scanning
timeFrame: 4 months
measure: Number of Circulating Tumour Cells (CTC) (in Patients Included in Ile de France Centres Only)
timeFrame: 4 months
measure: Number of Circulating Endothelial Cells (CEC) of Tumour Blood Cells (in Patients Included in Ile de France Centres Only)
timeFrame: 4 months
measure: Number of Patients With CECs, CTCs and Gene Signature Profile of CTCs
timeFrame: 4 months
Other outcomes:
Locations:
city: Bordeaux Cedex
country: France
facility: Research Site
city: Creteil
country: France
facility: Research Site
city: Paris
country: France
facility: Research Site
city: Reims Cedex
country: France
facility: Research Site
city: Villejuif
country: France
facility: Research Site
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: