Prostate CancerPhase 2NCT00659438
Efficacy and Safety of Zactima™ in Patients With Castration-refractory Metastatic Prostate Cancer
A Phase 2 study testing ZD6474 (Vandetanib) and Bicalutamide in people with Prostate Cancer, run by Genzyme, a Sanofi Company at 5 sites in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostate Cancer
- What is being tested?
- ZD6474 (Vandetanib) and Bicalutamide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 95 participants
- Where
- 5 sitesFrance
- Study dates
- Feb 2008to Jul 2011
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 .
Who cannot join
- 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).
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
France5 sites
Research Site
Bordeaux
Research Site
Créteil
Research Site
Paris
Research Site
Reims
Research Site
Villejuif
About this study
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
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.
- Conditions
- Prostate Cancer
- Being tested
- ZD6474 (Vandetanib), Bicalutamide, Placebo
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZD6474 (Vandetanib)Drug
Also called Zactima
300mg orally, once daily
BicalutamideDrug
Also called Casodex
150mg orally, once daily
PlaceboDrug
orally, once daily
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Bicalutamide 150mg + ZD6474 300mg Receives: Drug: ZD6474 (Vandetanib); Drug: Bicalutamide |
| 2 | Placebo comparator | Bicalutamide 150mg + placebo Receives: Drug: Bicalutamide; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 4 months
Secondary outcomes (8)
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.
Measured: 4 months
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.
Measured: 4 months
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.
Measured: 4 months
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.
Measured: End of study (July 2011)
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.
Measured: 4 months
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
Measured: 4 months
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.
Measured: 4 months
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.
Measured: 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Apr 2008 (estimated)
- Study startFeb 2008
- Primary completionNov 2010
- Study completionJul 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 95 participants (actual)
Sponsor and investigators
- Lead sponsor
- Genzyme, a Sanofi Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Sciences & Operations, Study director, Sanofi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00659438
- Sponsor's protocol ID
- D4200C00080
- Other IDs
- 2007-001891-35
- Status last verified
- Oct 2016
- First submitted
- 10 Apr 2008
- Last updated
- 5 Dec 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 5 Dec 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00659438
- Acronym / sponsor ID
- D4200C00080
- Conditions
- Prostate Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 95 participants (actual)
- Lead sponsor
- Genzyme, a Sanofi CompanyIndustry (pharma, biotech, devices)
- Study start
- Feb 2008
- Primary completion
- Nov 2010 (actual)
- Study completion
- Jul 2011 (actual)
- First posted
- 16 Apr 2008 (estimated)
- Results
- Posted 18 Jul 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: ZD6474 (Vandetanib), Drug: BicalutamideBicalutamide 150mg + ZD6474 300mg |
| 2 | Placebo comparator | Drug: Bicalutamide, Drug: PlaceboBicalutamide 150mg + placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 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 .
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ZD6474 (Vandetanib)Also: Zactima300mg orally, once daily | Drug | 1 |
| BicalutamideAlso: Casodex150mg orally, once daily | Drug | 1, 2 |
| Placeboorally, once daily | Drug | 2 |
Primary outcome
Prostate Specific Antigen (PSA) Progression Free Rate at 4 Months
Time frame: 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)
8 secondary outcomes
Progression Free Survival (PFS) at 4 Months (Instead of Time to PSA Progression)
Time frame: 4 months
Progression Free Survival (PFS) at 4 Months (Instead of Time to Onset of Cancer-related Symptoms)
Time frame: 4 months
PSA Response Rate
Time frame: 4 months
Overall Survival (OS)
Time frame: End of study (July 2011)
Progression Rate From the Radionuclide Bone Scanning
Time frame: 4 months
Number of Circulating Tumour Cells (CTC) (in Patients Included in Ile de France Centres Only)
Time frame: 4 months
Number of Circulating Endothelial Cells (CEC) of Tumour Blood Cells (in Patients Included in Ile de France Centres Only)
Time frame: 4 months
Number of Patients With CECs, CTCs and Gene Signature Profile of CTCs
Time frame: 4 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Dec 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Sciences & Operations study director
Sanofi
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ZD6474 (Vandetanib) and Bicalutamide in people with Prostate Cancer, run by Genzyme, a Sanofi Company at 5 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Dec 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Jul 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Prostate Specific Antigen (PSA) Progression Free Rate at 4 Months (time frame: 4 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Dec 2016.