search
Back to results

Efficacy and Safety of Zactima™ in Patients With Castration-refractory Metastatic Prostate Cancer

Primary Purpose

Prostate Cancer

Status
Completed
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
ZD6474 (Vandetanib)
Bicalutamide
Placebo
Sponsored by
Genzyme, a Sanofi Company
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Prostate Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

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).

Sites / Locations

  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

1

2

Arm Description

Bicalutamide 150mg + ZD6474 300mg

Bicalutamide 150mg + placebo

Outcomes

Primary Outcome Measures

Prostate Specific Antigen (PSA) Progression Free Rate at 4 Months
To assess the effect of vandetanib on biological progression free rate based on PSA level (assessable set). PSA progression free rate defined as the number of participants with : After decline from baseline: a 25% increase above the nadir No decline from baseline: a 25% increase above the baseline (min. increase of 2 ng/mL)

Secondary Outcome Measures

Progression Free Survival (PFS) at 4 Months (Instead of Time to PSA Progression)
Due to the difficulties to assess biological progression date when clinical progression has occurred first, and because of the non-assessment of the clinical progression after treatment discontinuation, Time to PSA progression was not evaluated. PFS was evaluated instead, whether biological or clinical progression.
Progression Free Survival (PFS) at 4 Months (Instead of Time to Onset of Cancer-related Symptoms)
Due to the difficulties to assess biological progression date when clinical progression has occurred first, and because of the non-assessment of the clinical progression after treatment discontinuation, Time to onset of cancer-related symptoms was not evaluated. PFS was evaluated instead, whether biological or clinical progression.
PSA Response Rate
To investigate the effect of vandetanib on the PSA response rate. PSA response rate defined by the number of participants with a PSA decrease relative to baseline of at least 50%. A minimum decrease of 2 ng/mL in absolute value and a confirmation on at least 2 consecutive occasions (at least 4 weeks apart) were requested.
Overall Survival (OS)
To investigate the effect of vandetanib on overall survival. Patients alive at the time of the statistical analysis were censored at the time they were last known to be alive. Due to censored data, median overall survival in the placebo group cannot be calculated. OS defined as the number of participants who were alive.
Progression Rate From the Radionuclide Bone Scanning
To describe the effect of vandetanib on progression rate from the radionuclide bone scanning in a sub-group of patients who had a bone scan within 3 to 6 months after 1st treatment dose. Number of participants with at least 2 new lesions on the radionuclide bone scan compared to baseline assessment were counted for calculation of progression rate.
Number of Circulating Tumour Cells (CTC) (in Patients Included in Ile de France Centres Only)
To investigate the effect of vandetanib on CTC. Numbering of CTCs to be performed at baseline, 1 week, 1 and 2 months after randomisation. This study was proposed only to patients followed in a study centre located in Ile de France. Correlation between the number of CTCs and PSA response was to be estimated after 1 week, 1 and 2 months of treatment
Number of Circulating Endothelial Cells (CEC) of Tumour Blood Cells (in Patients Included in Ile de France Centres Only)
To investigate the effect of vandetanib on CEC. Numbering of CECs was to be performed at baseline, 1 week, 1 month and 2 months after randomisation. Correlation between the number of CECs and PSA response was to be estimated after 1 week, 1 month and 2 months of treatment.
Number of Patients With CECs, CTCs and Gene Signature Profile of CTCs
To investigate the relationship between response to vandetanib, CTCs and CECs. To investigate gene signature profile of antiangiogenic response by gene micro-array analysis of CTCs. Gene signature profile of CTCs was aimed to be compared before and after 2 months of treatment. No blood sample has been taken for the study, and so results on CTCs, CECs of tumour vessels and gene and signature profiles of CTCs were not performed.

Full Information

First Posted
April 10, 2008
Last Updated
October 11, 2016
Sponsor
Genzyme, a Sanofi Company
search

1. Study Identification

Unique Protocol Identification Number
NCT00659438
Brief Title
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

2. Study Status

Record Verification Date
October 2016
Overall Recruitment Status
Completed
Study Start Date
February 2008 (undefined)
Primary Completion Date
November 2010 (Actual)
Study Completion Date
July 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Genzyme, a Sanofi Company

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
95 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Description
Bicalutamide 150mg + ZD6474 300mg
Arm Title
2
Arm Type
Placebo Comparator
Arm Description
Bicalutamide 150mg + placebo
Intervention Type
Drug
Intervention Name(s)
ZD6474 (Vandetanib)
Other Intervention Name(s)
Zactima
Intervention Description
300mg orally, once daily
Intervention Type
Drug
Intervention Name(s)
Bicalutamide
Other Intervention Name(s)
Casodex
Intervention Description
150mg orally, once daily
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
orally, once daily
Primary Outcome Measure Information:
Title
Prostate Specific Antigen (PSA) Progression Free Rate at 4 Months
Description
To assess the effect of vandetanib on biological progression free rate based on PSA level (assessable set). PSA progression free rate defined as the number of participants with : After decline from baseline: a 25% increase above the nadir No decline from baseline: a 25% increase above the baseline (min. increase of 2 ng/mL)
Time Frame
4 months
Secondary Outcome Measure Information:
Title
Progression Free Survival (PFS) at 4 Months (Instead of Time to PSA Progression)
Description
Due to the difficulties to assess biological progression date when clinical progression has occurred first, and because of the non-assessment of the clinical progression after treatment discontinuation, Time to PSA progression was not evaluated. PFS was evaluated instead, whether biological or clinical progression.
Time Frame
4 months
Title
Progression Free Survival (PFS) at 4 Months (Instead of Time to Onset of Cancer-related Symptoms)
Description
Due to the difficulties to assess biological progression date when clinical progression has occurred first, and because of the non-assessment of the clinical progression after treatment discontinuation, Time to onset of cancer-related symptoms was not evaluated. PFS was evaluated instead, whether biological or clinical progression.
Time Frame
4 months
Title
PSA Response Rate
Description
To investigate the effect of vandetanib on the PSA response rate. PSA response rate defined by the number of participants with a PSA decrease relative to baseline of at least 50%. A minimum decrease of 2 ng/mL in absolute value and a confirmation on at least 2 consecutive occasions (at least 4 weeks apart) were requested.
Time Frame
4 months
Title
Overall Survival (OS)
Description
To investigate the effect of vandetanib on overall survival. Patients alive at the time of the statistical analysis were censored at the time they were last known to be alive. Due to censored data, median overall survival in the placebo group cannot be calculated. OS defined as the number of participants who were alive.
Time Frame
End of study (July 2011)
Title
Progression Rate From the Radionuclide Bone Scanning
Description
To describe the effect of vandetanib on progression rate from the radionuclide bone scanning in a sub-group of patients who had a bone scan within 3 to 6 months after 1st treatment dose. Number of participants with at least 2 new lesions on the radionuclide bone scan compared to baseline assessment were counted for calculation of progression rate.
Time Frame
4 months
Title
Number of Circulating Tumour Cells (CTC) (in Patients Included in Ile de France Centres Only)
Description
To investigate the effect of vandetanib on CTC. Numbering of CTCs to be performed at baseline, 1 week, 1 and 2 months after randomisation. This study was proposed only to patients followed in a study centre located in Ile de France. Correlation between the number of CTCs and PSA response was to be estimated after 1 week, 1 and 2 months of treatment
Time Frame
4 months
Title
Number of Circulating Endothelial Cells (CEC) of Tumour Blood Cells (in Patients Included in Ile de France Centres Only)
Description
To investigate the effect of vandetanib on CEC. Numbering of CECs was to be performed at baseline, 1 week, 1 month and 2 months after randomisation. Correlation between the number of CECs and PSA response was to be estimated after 1 week, 1 month and 2 months of treatment.
Time Frame
4 months
Title
Number of Patients With CECs, CTCs and Gene Signature Profile of CTCs
Description
To investigate the relationship between response to vandetanib, CTCs and CECs. To investigate gene signature profile of antiangiogenic response by gene micro-array analysis of CTCs. Gene signature profile of CTCs was aimed to be compared before and after 2 months of treatment. No blood sample has been taken for the study, and so results on CTCs, CECs of tumour vessels and gene and signature profiles of CTCs were not performed.
Time Frame
4 months

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Sciences & Operations
Organizational Affiliation
Sanofi
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Bordeaux Cedex
Country
France
Facility Name
Research Site
City
Creteil
Country
France
Facility Name
Research Site
City
Paris
Country
France
Facility Name
Research Site
City
Reims Cedex
Country
France
Facility Name
Research Site
City
Villejuif
Country
France

12. IPD Sharing Statement

Learn more about this trial

Efficacy and Safety of Zactima™ in Patients With Castration-refractory Metastatic Prostate Cancer

We'll reach out to this number within 24 hrs