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Trial record 1 of 1 for:    D4200C00080
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Efficacy and Safety of Zactima™ in Patients With Castration-refractory Metastatic Prostate Cancer

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ClinicalTrials.gov Identifier: NCT00659438
Recruitment Status : Completed
First Posted : April 16, 2008
Results First Posted : July 18, 2012
Last Update Posted : December 5, 2016
Sponsor:
Information provided by (Responsible Party):
Sanofi ( Genzyme, a Sanofi Company )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Prostate Cancer
Interventions Drug: ZD6474 (Vandetanib)
Drug: Bicalutamide
Drug: Placebo
Enrollment 95
Recruitment Details From February 4th, 2008 to April 26th, 2010, 8 centers in France.
Pre-assignment Details 110 participants screened; 95 participants were randomized to receive either bicalutamide 150 mg + vandetanib 300 mg once daily oral dose or bicalutamide 150 mg + placebo.
Arm/Group Title Vandetanib Placebo
Hide Arm/Group Description Bicalutamide 150mg + Vandetanib (ZD6474) 300mg Bicalutamide 150mg + placebo
Period Title: Overall Study
Started 47 48
Assessable Set : Primary Analysis 44 45
Secondary Analysis Set 47 48
Safety Analysis Set 48 [1] 47
Completed 33 40
Not Completed 14 8
Reason Not Completed
Withdrawal by Subject             2             2
Death             11             6
Lost to Follow-up             1             0
[1]
One patient randomized to placebo was accounted in vandetanib group as he mistakenly received drug
Arm/Group Title Vandetanib Placebo Total
Hide Arm/Group Description Bicalutamide 150mg + Vandetanib (ZD6474) 300mg Bicalutamide 150mg + placebo Total of all reporting groups
Overall Number of Baseline Participants 47 48 95
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 47 participants 48 participants 95 participants
70.77  (7.68) 72.23  (6.92) 71.51  (7.30)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 47 participants 48 participants 95 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
Male
47
 100.0%
48
 100.0%
95
 100.0%
1.Primary Outcome
Title Prostate Specific Antigen (PSA) Progression Free Rate at 4 Months
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Vandetanib Placebo
Hide Arm/Group Description:
Bicalutamide 150mg + Vandetanib (ZD6474) 300mg
Bicalutamide 150mg + placebo
Overall Number of Participants Analyzed 44 45
Measure Type: Number
Unit of Measure: Participants
8 7
2.Secondary Outcome
Title Progression Free Survival (PFS) at 4 Months (Instead of Time to PSA Progression)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Vandetanib Placebo
Hide Arm/Group Description:
Bicalutamide 150mg + Vandetanib (ZD6474) 300mg
Bicalutamide 150mg + placebo
Overall Number of Participants Analyzed 47 48
Median (95% Confidence Interval)
Unit of Measure: weeks
12.2
(11.8 to 12.4)
12.8
(12.2 to 13.6)
3.Secondary Outcome
Title Progression Free Survival (PFS) at 4 Months (Instead of Time to Onset of Cancer-related Symptoms)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Vandetanib Placebo
Hide Arm/Group Description:
Bicalutamide 150mg + Vandetanib (ZD6474) 300mg
Bicalutamide 150mg + placebo
Overall Number of Participants Analyzed 47 48
Median (95% Confidence Interval)
Unit of Measure: weeks
12.2
(11.8 to 12.4)
12.8
(12.2 to 13.6)
4.Secondary Outcome
Title PSA Response Rate
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Vandetanib Placebo
Hide Arm/Group Description:
Bicalutamide 150mg + Vandetanib (ZD6474) 300mg
Bicalutamide 150mg + placebo
Overall Number of Participants Analyzed 47 48
Measure Type: Number
Unit of Measure: Participants
3 5
5.Secondary Outcome
Title Overall Survival (OS)
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Vandetanib Placebo
Hide Arm/Group Description:
Bicalutamide 150mg + Vandetanib (ZD6474) 300mg
Bicalutamide 150mg + placebo
Overall Number of Participants Analyzed 47 48
Measure Type: Number
Unit of Measure: participants
32 35
6.Secondary Outcome
Title Progression Rate From the Radionuclide Bone Scanning
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Vandetanib Placebo
Hide Arm/Group Description:
Bicalutamide 150mg + Vandetanib (ZD6474) 300mg
Bicalutamide 150mg + placebo
Overall Number of Participants Analyzed 10 13
Measure Type: Number
Unit of Measure: Participants
3 4
7.Secondary Outcome
Title Number of Circulating Tumour Cells (CTC) (in Patients Included in Ile de France Centres Only)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
This part of the study was proposed only to patients followed in one study centre located in Ile de France and finally no blood sample has been taken at this centre. So no data on CTCs, CECs were collected and no analysis was performed.
Arm/Group Title Vandetanib Placebo
Hide Arm/Group Description:
Bicalutamide 150mg + Vandetanib (ZD6474) 300mg
Bicalutamide 150mg + placebo
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
8.Secondary Outcome
Title Number of Circulating Endothelial Cells (CEC) of Tumour Blood Cells (in Patients Included in Ile de France Centres Only)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
This part of the study was proposed only to patients followed in one study centre located in Ile de France and finally no blood sample has been taken at this centre. So no data on CTCs, CECs were collected and no analysis was performed.
Arm/Group Title Vandetanib Placebo
Hide Arm/Group Description:
Bicalutamide 150mg + Vandetanib (ZD6474) 300mg
Bicalutamide 150mg + placebo
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
9.Secondary Outcome
Title Number of Patients With CECs, CTCs and Gene Signature Profile of CTCs
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Vandetanib Placebo
Hide Arm/Group Description:
Bicalutamide 150mg + Vandetanib (ZD6474) 300mg
Bicalutamide 150mg + placebo
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame [Not Specified]
Adverse Event Reporting Description Safety analysis set is composed with all randomized subjects who received at least one dose of treatment. One patient mistakenly received vandetanib during 3 days while randomized to placebo. This patient was accounted in the vandetanib group in the safety population. So, safety analysis set is composed with 48 Vandetanib and 47 placebo patients.
 
Arm/Group Title Vandetanib Placebo
Hide Arm/Group Description Bicalutamide 150mg + Vandetanib (ZD6474) 300mg Bicalutamide 150mg + placebo
All-Cause Mortality
Vandetanib Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Vandetanib Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   17/48 (35.42%)   4/47 (8.51%) 
Blood and lymphatic system disorders     
Febrile bone marrow aplasia * 1  0/48 (0.00%)  1/47 (2.13%) 
Anaemia * 1  1/48 (2.08%)  0/47 (0.00%) 
Cardiac disorders     
Torsade de pointes * 1  1/48 (2.08%)  0/47 (0.00%) 
Ventricular extrasystoles * 1  1/48 (2.08%)  0/47 (0.00%) 
Gastrointestinal disorders     
Anal fissure * 1  1/48 (2.08%)  0/47 (0.00%) 
Ileus * 1  1/48 (2.08%)  0/47 (0.00%) 
Intestinal obstruction * 1  0/48 (0.00%)  1/47 (2.13%) 
General disorders     
Death * 1  1/48 (2.08%)  0/47 (0.00%) 
Disease progression * 1  1/48 (2.08%)  0/47 (0.00%) 
Performance status decrease * 1  1/48 (2.08%)  0/47 (0.00%) 
Infections and infestations     
Sepsis * 1  1/48 (2.08%)  0/47 (0.00%) 
Bronchopneumonia * 1  1/48 (2.08%)  0/47 (0.00%) 
Pneumonia * 1  1/48 (2.08%)  0/47 (0.00%) 
Septic shock * 1  0/48 (0.00%)  1/47 (2.13%) 
Injury, poisoning and procedural complications     
Ankle fracture * 1  0/48 (0.00%)  1/47 (2.13%) 
Investigations     
Electrocardiogram QT prolonged * 1  2/48 (4.17%)  0/47 (0.00%) 
Musculoskeletal and connective tissue disorders     
Back pain * 1  0/48 (0.00%)  1/47 (2.13%) 
Spondylitis * 1  1/48 (2.08%)  0/47 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Chronic lymphocytic leukaemia * 1  1/48 (2.08%)  0/47 (0.00%) 
Prostate cancer * 1  0/48 (0.00%)  1/47 (2.13%) 
Nervous system disorders     
Cerebrovascular accident * 1  2/48 (4.17%)  0/47 (0.00%) 
Cerebral haemorrhage * 1  1/48 (2.08%)  0/47 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Pulmonary embolism * 1  1/48 (2.08%)  0/47 (0.00%) 
Skin and subcutaneous tissue disorders     
Drug eruption * 1  1/48 (2.08%)  0/47 (0.00%) 
Toxic skin eruption * 1  1/48 (2.08%)  0/47 (0.00%) 
Photosensitivity reaction * 1  2/48 (4.17%)  0/47 (0.00%) 
Rash erythematous * 1  1/48 (2.08%)  0/47 (0.00%) 
Surgical and medical procedures     
Stent placement * 1  1/48 (2.08%)  0/47 (0.00%) 
Vascular disorders     
Hypertension * 1  1/48 (2.08%)  0/47 (0.00%) 
Hypertensive crisis * 1  1/48 (2.08%)  0/47 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 13.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Vandetanib Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   47/48 (97.92%)   47/47 (100.00%) 
Gastrointestinal disorders     
Diarrhoea  1  21/48 (43.75%)  5/47 (10.64%) 
Constipation  1  8/48 (16.67%)  8/47 (17.02%) 
Nausea  1  9/48 (18.75%)  0/47 (0.00%) 
Abdominal pain  1  4/48 (8.33%)  3/47 (6.38%) 
Abdominal pain upper  1  3/48 (6.25%)  1/47 (2.13%) 
General disorders     
Fatigue  1  2/48 (4.17%)  3/47 (6.38%) 
Asthenia  1  20/48 (41.67%)  19/47 (40.43%) 
Chest pain  1  0/48 (0.00%)  3/47 (6.38%) 
Pain  1  0/48 (0.00%)  3/47 (6.38%) 
Hepatobiliary disorders     
Cytolytic hepatitis  1  4/48 (8.33%)  0/47 (0.00%) 
Infections and infestations     
Urinary tra ct infection  1  4/48 (8.33%)  1/47 (2.13%) 
Rhinitis  1  1/48 (2.08%)  3/47 (6.38%) 
Investigations     
Electrocardiogram QT prolonged  1  8/48 (16.67%)  1/47 (2.13%) 
Weight decreased  1  5/48 (10.42%)  1/47 (2.13%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  7/48 (14.58%)  6/47 (12.77%) 
Arthralgia  1  3/48 (6.25%)  7/47 (14.89%) 
Musculoskeletal pain  1  3/48 (6.25%)  5/47 (10.64%) 
Myalgia  1  2/48 (4.17%)  4/47 (8.51%) 
Bone pain  1  2/48 (4.17%)  3/47 (6.38%) 
Pain in extremity  1  1/48 (2.08%)  4/47 (8.51%) 
Nervous system disorders     
Dizziness  1  5/48 (10.42%)  5/47 (10.64%) 
Headache  1  3/48 (6.25%)  4/47 (8.51%) 
Sciatica  1  3/48 (6.25%)  1/47 (2.13%) 
Psychiatric disorders     
Insomnia  1  4/48 (8.33%)  6/47 (12.77%) 
Anxiety  1  2/48 (4.17%)  7/47 (14.89%) 
Depression  1  4/48 (8.33%)  0/47 (0.00%) 
Renal and urinary disorders     
Haematuria  1  2/48 (4.17%)  3/47 (6.38%) 
Pollakiuria  1  2/48 (4.17%)  3/47 (6.38%) 
Dysuria  1  1/48 (2.08%)  3/47 (6.38%) 
Reproductive system and breast disorders     
Gynaecomastia  1  7/48 (14.58%)  4/47 (8.51%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  4/48 (8.33%)  2/47 (4.26%) 
Epistaxis  1  3/48 (6.25%)  1/47 (2.13%) 
Skin and subcutaneous tissue disorders     
Photosensitivity reaction  1  5/48 (10.42%)  0/47 (0.00%) 
Dry Skin  1  4/48 (8.33%)  1/47 (2.13%) 
Pruritus  1  4/48 (8.33%)  1/47 (2.13%) 
Rash  1  4/48 (8.33%)  1/47 (2.13%) 
Erythema  1  3/48 (6.25%)  1/47 (2.13%) 
Rash erythematous  1  3/48 (6.25%)  0/47 (0.00%) 
Skin fissures  1  3/48 (6.25%)  0/47 (0.00%) 
Vascular disorders     
Hot flush  1  11/48 (22.92%)  11/47 (23.40%) 
Hypertension  1  14/48 (29.17%)  5/47 (10.64%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 13.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such presentation/publication for comment at least 30 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.
Results Point of Contact
Name/Title: Trial Transparency Team
Organization: Sanofi
Responsible Party: Sanofi ( Genzyme, a Sanofi Company )
ClinicalTrials.gov Identifier: NCT00659438     History of Changes
Other Study ID Numbers: D4200C00080
2007-001891-35 ( EudraCT Number )
First Submitted: April 10, 2008
First Posted: April 16, 2008
Results First Submitted: November 14, 2011
Results First Posted: July 18, 2012
Last Update Posted: December 5, 2016