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| ID | Type | Description | Link |
|---|---|---|---|
| 2007-001891-35 | EudraCT Number |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Experimental | Bicalutamide 150mg + ZD6474 300mg |
|
| 2 | Placebo Comparator | Bicalutamide 150mg + placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ZD6474 (Vandetanib) | Drug | 300mg orally, once daily |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 :
| 4 months |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 4 months |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Sciences & Operations | Sanofi | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Bordeaux | France | ||||
| Research Site |
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.
From February 4th, 2008 to April 26th, 2010, 8 centers in France.
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| ID | Title | Description |
|---|---|---|
| FG000 | Vandetanib | Bicalutamide 150mg + Vandetanib (ZD6474) 300mg |
| FG001 | Placebo | Bicalutamide 150mg + placebo |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Vandetanib | Bicalutamide 150mg + Vandetanib (ZD6474) 300mg |
| BG001 | Placebo | Bicalutamide 150mg + placebo |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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 :
| Posted | Number | Participants | 4 months |
|
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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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Vandetanib | Bicalutamide 150mg + Vandetanib (ZD6474) 300mg |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 13.1 | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Fatigue | General disorders | MedDRA 13.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Trial Transparency Team | Sanofi | Contact-US@sanofi.com |
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| ID | Term |
|---|---|
| D011471 | Prostatic Neoplasms |
| ID | Term |
|---|---|
| D005834 | Genital Neoplasms, Male |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| C452423 | vandetanib |
| C053541 | bicalutamide |
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| Bicalutamide | Drug | 150mg orally, once daily |
|
|
| Placebo | Drug | orally, once daily |
|
| 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. | 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. | 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. | 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. | 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 | 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. | 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. | 4 months |
| Créteil |
| France |
| Research Site | Paris | France |
| Research Site | Reims | France |
| Research Site | Villejuif | France |
| Lost to Follow-up |
|
| BG002 |
| Total |
Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Units | Counts |
|---|---|
| Participants |
|
|
| Secondary | 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. | Posted | Median | 95% Confidence Interval | weeks | 4 months |
|
|
|
| Secondary | 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. | Posted | Median | 95% Confidence Interval | weeks | 4 months |
|
|
|
| Secondary | 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. | Posted | Number | Participants | 4 months |
|
|
|
| Secondary | 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. | Posted | Number | participants | End of study (July 2011) |
|
|
|
| Secondary | 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. | Posted | Number | Participants | 4 months |
|
|
|
| Secondary | 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 | 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. | Posted | 4 months |
|
|
| Secondary | 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. | 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. | Posted | 4 months |
|
|
| Secondary | 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. | Posted | 4 months |
|
|
| 17 |
| 48 |
| 47 |
| 48 |
| EG001 | Placebo | Bicalutamide 150mg + placebo | 4 | 47 | 47 | 47 |
| Drug eruption | Skin and subcutaneous tissue disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Sepsis | Infections and infestations | MedDRA 13.1 | Non-systematic Assessment |
|
| Toxic skin eruption | Skin and subcutaneous tissue disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Anal fissure | Gastrointestinal disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Bronchopneumonia | Infections and infestations | MedDRA 13.1 | Non-systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA 13.1 | Non-systematic Assessment |
|
| Death | General disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Cerebrovascular accident | Nervous system disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Ileus | Gastrointestinal disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Septic shock | Infections and infestations | MedDRA 13.1 | Non-systematic Assessment |
|
| Febrile bone marrow aplasia | Blood and lymphatic system disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Photosensitivity reaction | Skin and subcutaneous tissue disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Chronic lymphocytic leukaemia | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 13.1 | Non-systematic Assessment |
|
| Anaemia | Blood and lymphatic system disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Rash erythematous | Skin and subcutaneous tissue disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Spondylitis | Musculoskeletal and connective tissue disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Cerebral haemorrhage | Nervous system disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Torsade de pointes | Cardiac disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Electrocardiogram QT prolonged | Investigations | MedDRA 13.1 | Non-systematic Assessment |
|
| Hypertensive crisis | Vascular disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Ventricular extrasystoles | Cardiac disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Stent placement | Surgical and medical procedures | MedDRA 13.1 | Non-systematic Assessment |
|
| Intestinal obstruction | Gastrointestinal disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Ankle fracture | Injury, poisoning and procedural complications | MedDRA 13.1 | Non-systematic Assessment |
|
| Disease progression | General disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Performance status decrease | General disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Prostate cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 13.1 | Non-systematic Assessment |
|
| Asthenia | General disorders | MedDRA 13.1 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 13.1 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 13.1 | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 13.1 | Systematic Assessment |
|
| Hot flush | Vascular disorders | MedDRA 13.1 | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA 13.1 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 13.1 | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA 13.1 | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA 13.1 | Systematic Assessment |
|
| Photosensitivity reaction | Skin and subcutaneous tissue disorders | MedDRA 13.1 | Systematic Assessment |
|
| Electrocardiogram QT prolonged | Investigations | MedDRA 13.1 | Systematic Assessment |
|
| Weight decreased | Investigations | MedDRA 13.1 | Systematic Assessment |
|
| Gynaecomastia | Reproductive system and breast disorders | MedDRA 13.1 | Systematic Assessment |
|
| Chest pain | General disorders | MedDRA 13.1 | Systematic Assessment |
|
| Pain | General disorders | MedDRA 13.1 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 13.1 | Systematic Assessment |
|
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA 13.1 | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 13.1 | Systematic Assessment |
|
| Urinary tra ct infection | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
|
| Rhinitis | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 13.1 | Systematic Assessment |
|
| Sciatica | Nervous system disorders | MedDRA 13.1 | Systematic Assessment |
|
| Depression | Psychiatric disorders | MedDRA 13.1 | Systematic Assessment |
|
| Dry Skin | Skin and subcutaneous tissue disorders | MedDRA 13.1 | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 13.1 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 13.1 | Systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA 13.1 | Systematic Assessment |
|
| Rash erythematous | Skin and subcutaneous tissue disorders | MedDRA 13.1 | Systematic Assessment |
|
| Skin fissures | Skin and subcutaneous tissue disorders | MedDRA 13.1 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 13.1 | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 13.1 | Systematic Assessment |
|
| Haematuria | Renal and urinary disorders | MedDRA 13.1 | Systematic Assessment |
|
| Pollakiuria | Renal and urinary disorders | MedDRA 13.1 | Systematic Assessment |
|
| Dysuria | Renal and urinary disorders | MedDRA 13.1 | Systematic Assessment |
|
| Cytolytic hepatitis | Hepatobiliary disorders | MedDRA 13.1 | Systematic Assessment |
|
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.
| D005832 |
| Genital Diseases, Male |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D011469 | Prostatic Diseases |
| D052801 | Male Urogenital Diseases |