E3-Hormone Refractory Prostrate Cancer Taxotere Combination

• Sponsor: Sanofi (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00498797
• Collaborator: Genzyme, a Sanofi Company (Industry)
• Enrollment: 86
• Locations: 11
• Duration (Months): 33
• Patients Per Site: 7.8
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether treatment with Zactima (vandetanib) in combination with Docetaxel and Prednisolone is more effective than the standard Docetaxel and Prednisolone alone for prostate cancer, in patients with Hormone refractory prostate cancer who have not previously received chemotherapy.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer; Metastatic; Hormone Refractory	Drug: Zactima (vandetanib); Drug: Docetaxel; Drug: Prednisolone	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 86 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double
• Primary Purpose: Treatment
• Official Title: A Phase II, Double-blind, Placebo-controlled, Randomised Study to Assess the Efficacy and Safety of Docetaxel (Taxotere)/Prednisolone/ZD6474 vs Docetaxel/Prednisolone/Placebo in Patients With Hormone Refractory Prostrate Cancer (HRPC)
• Study Start Date: Dec 1, 2005
• Actual Primary Completion Date: Jul 1, 2007
• Actual Study Completion Date: Sep 1, 2008

Outcome Measures

Primary Outcome Measures

1. Prostate Specific Antigen (PSA) Response [PSA measurements were to be performed at screening, at baseline (>2 weeks after screening) and every 3 weeks during the study. Any response was to be confirmed 2-4 weeks after the initial assessment of a 50% fall in PSA from baseline]

   Prostate Specific Antigen (PSA) response was defined as a reduction of at least 50% from baseline at any assessment, confirmed by a second assessment 2-4 weeks after the initial response

Secondary Outcome Measures

1. Number of Patients With an Objective Disease Progression Event [RECIST tumour assessments carried out at screening and then as per site clinical practice until objective progression. The only additional mandatory tumour assessment visit is at the point of data cut-off (21 July 2007 or up to 7 days in advance of DCO)]

   Number of patients with objective disease progression or death (by any cause in the absence of objective progression)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Metastatic hormone refractory prostate cancer defined as those patients with evidence of progression of disease in spite of castrate levels of testosterone indicated by rising levels of PSA

• No previous chemotherapy although those patients that have received estramustine can enter the study provided the estramustine was stopped 3 weeks before dosing of study drug

• screening PSA values >20ng/ml. this must be confirmed by two separate measurements at least 2 weeks apart

Exclusion Criteria:

• Treatment within 4 weeks before randomization and/or whilst on study, treatment with the following: 1)non-approved or experimental drug, 2)treatment with a drug with similar mechanism of action to ZD6474

• concurrent treatment with other anticancer agents, othr than docetaxel and prednisolone as defined in the protocol

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research site	Rio de Janeiro		Brazil
2	Research Site	Sao Paulo		Brazil
3	Research Site	Hamburg		Germany
4	Research Site	Hannover		Germany
5	Research Site	Kassel		Germany
6	Research Site	Tubingen		Germany
7	Research Site	Budapest		Hungary
8	Research Site	Bloemfontein		South Africa
9	Research Site	Cape Town		South Africa
10	Research Site	Umea		Sweden
11	Research Site	Uppsala		Sweden

Sponsors and Collaborators

• Sanofi
• Genzyme, a Sanofi Company

Investigators

• Study Director: Clinical Sciences & Operations, Sanofi

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sanofi
• ClinicalTrials.gov Identifier: NCT00498797
• Other Study ID Numbers: D4200C00055; 2005-003593-16
• First Posted: Jul 10, 2007
• Last Update Posted: Oct 7, 2016
• Last Verified: Aug 1, 2016

• Keywords provided by Sanofi: prostate cancer; zactima; vandetanib; metastatic
• Additional relevant MeSH terms: Prostatic Neoplasms; Prednisolone; Docetaxel

Study Results

Participant Flow

Recruitment Details	First patient randomised 24 January 2006, last patient randomised 24 Nov 2006, data cut off data 21 July 2007

Arm/Group Title	Vandetanib	Placebo
Arm/Group Description	docetaxel/prednisolone/vandetanib	docetaxel/prednisolone/placebo
Period Title: Overall Study
STARTED	43	43
COMPLETED	5	14
NOT COMPLETED	38	29

Baseline Characteristics

Arm/Group Title	Vandetanib	Placebo	Total
Arm/Group Description	docetaxel/prednisolone/vandetanib	docetaxel/prednisolone/placebo	Total of all reporting groups
Overall Participants	43	43	86
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	67	67	67
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	43 100%	43 100%	86 100%

Outcome Measures

1. Primary Outcome

Title	Prostate Specific Antigen (PSA) Response
Description	Prostate Specific Antigen (PSA) response was defined as a reduction of at least 50% from baseline at any assessment, confirmed by a second assessment 2-4 weeks after the initial response
Time Frame	PSA measurements were to be performed at screening, at baseline (>2 weeks after screening) and every 3 weeks during the study. Any response was to be confirmed 2-4 weeks after the initial assessment of a 50% fall in PSA from baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vandetanib	Placebo
Arm/Group Description	docetaxel/prednisolone/vandetanib	docetaxel/prednisolone/placebo
Measure Participants	43	43
Number [Participants]	17 39.5%	29 67.4%

2. Secondary Outcome

Title	Number of Patients With an Objective Disease Progression Event
Description	Number of patients with objective disease progression or death (by any cause in the absence of objective progression)
Time Frame	RECIST tumour assessments carried out at screening and then as per site clinical practice until objective progression. The only additional mandatory tumour assessment visit is at the point of data cut-off (21 July 2007 or up to 7 days in advance of DCO)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vandetanib	Placebo
Arm/Group Description	docetaxel/prednisolone/vandetanib	docetaxel/prednisolone/placebo
Measure Participants	43	43
Number [Participants]	28 65.1%	26 60.5%

Adverse Events

Arm/Group Title	Vandetanib		Placebo
Arm/Group Description	docetaxel/prednisolone/vandetanib		docetaxel/prednisolone/placebo
All Cause Mortality
	Vandetanib		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Vandetanib		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	23/43 (53.5%)		15/43 (34.9%)
Blood and lymphatic system disorders
FEBRILE NEUTROPENIA	2/43 (4.7%)		1/43 (2.3%)
ANAEMIA	0/43 (0%)		1/43 (2.3%)
NEUTROPENIA	1/43 (2.3%)		0/43 (0%)
Cardiac disorders
ATRIAL FIBRILLATION	1/43 (2.3%)		1/43 (2.3%)
Eye disorders
BLINDNESS	1/43 (2.3%)		0/43 (0%)
Gastrointestinal disorders
CONSTIPATION	0/43 (0%)		1/43 (2.3%)
DIARRHOEA	0/43 (0%)		1/43 (2.3%)
DUODENAL ULCER HAEMORRHAGE	0/43 (0%)		1/43 (2.3%)
GASTRIC ULCER	1/43 (2.3%)		0/43 (0%)
LARGE INTESTINE PERFORATION	1/43 (2.3%)		0/43 (0%)
NAUSEA	0/43 (0%)		1/43 (2.3%)
VOMITING	1/43 (2.3%)		1/43 (2.3%)
General disorders
FATIGUE	0/43 (0%)		1/43 (2.3%)
PYREXIA	0/43 (0%)		1/43 (2.3%)
Hepatobiliary disorders
CHOLELITHIASIS	1/43 (2.3%)		0/43 (0%)
Infections and infestations
PNEUMONIA	3/43 (7%)		1/43 (2.3%)
DIVERTICULITIS	1/43 (2.3%)		0/43 (0%)
LOBAR PNEUMONIA	1/43 (2.3%)		0/43 (0%)
PERIRECTAL ABSCESS	1/43 (2.3%)		0/43 (0%)
SEPSIS	1/43 (2.3%)		0/43 (0%)
URINARY TRACT INFECTION	0/43 (0%)		1/43 (2.3%)
Injury, poisoning and procedural complications
STERNAL FRACTURE	0/43 (0%)		1/43 (2.3%)
Metabolism and nutrition disorders
DIABETES MELLITUS INADEQUATE CONTROL	1/43 (2.3%)		0/43 (0%)
HYPERGLYCAEMIA	1/43 (2.3%)		1/43 (2.3%)
HYPONATRAEMIA	1/43 (2.3%)		0/43 (0%)
Musculoskeletal and connective tissue disorders
BONE PAIN	1/43 (2.3%)		0/43 (0%)
BURSITIS	1/43 (2.3%)		0/43 (0%)
Nervous system disorders
EPILEPSY	1/43 (2.3%)		0/43 (0%)
PERIPHERAL SENSORY NEUROPATHY	0/43 (0%)		1/43 (2.3%)
Renal and urinary disorders
HYDRONEPHROSIS	0/43 (0%)		1/43 (2.3%)
RENAL FAILURE	1/43 (2.3%)		1/43 (2.3%)
Respiratory, thoracic and mediastinal disorders
PULMONARY EMBOLISM	2/43 (4.7%)		1/43 (2.3%)
BRONCHOSPASM	0/43 (0%)		1/43 (2.3%)
DYSPNOEA	0/43 (0%)		1/43 (2.3%)
Skin and subcutaneous tissue disorders
EXFOLIATIVE RASH	1/43 (2.3%)		0/43 (0%)
RASH ERYTHEMATOUS	1/43 (2.3%)		0/43 (0%)
TOXIC SKIN ERUPTION	1/43 (2.3%)		0/43 (0%)
Vascular disorders
DEEP VEIN THROMBOSIS	0/43 (0%)		1/43 (2.3%)
THROMBOPHLEBITIS	1/43 (2.3%)		0/43 (0%)
Other (Not Including Serious) Adverse Events
	Vandetanib		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	38/43 (88.4%)		39/43 (90.7%)
Blood and lymphatic system disorders
ANAEMIA	1/43 (2.3%)		5/43 (11.6%)
NEUTROPENIA	3/43 (7%)		4/43 (9.3%)
LEUKOPENIA	1/43 (2.3%)		3/43 (7%)
Cardiac disorders
PALPITATIONS	3/43 (7%)		0/43 (0%)
Ear and labyrinth disorders
VERTIGO	3/43 (7%)		1/43 (2.3%)
Eye disorders
LACRIMATION INCREASED	4/43 (9.3%)		7/43 (16.3%)
CONJUNCTIVITIS	1/43 (2.3%)		3/43 (7%)
Gastrointestinal disorders
NAUSEA	7/43 (16.3%)		16/43 (37.2%)
DIARRHOEA	10/43 (23.3%)		13/43 (30.2%)
CONSTIPATION	4/43 (9.3%)		10/43 (23.3%)
VOMITING	1/43 (2.3%)		7/43 (16.3%)
STOMATITIS	4/43 (9.3%)		4/43 (9.3%)
ABDOMINAL PAIN	1/43 (2.3%)		3/43 (7%)
DYSPEPSIA	3/43 (7%)		3/43 (7%)
General disorders
FATIGUE	16/43 (37.2%)		14/43 (32.6%)
ASTHENIA	5/43 (11.6%)		7/43 (16.3%)
OEDEMA PERIPHERAL	4/43 (9.3%)		7/43 (16.3%)
PYREXIA	1/43 (2.3%)		4/43 (9.3%)
CHILLS	3/43 (7%)		1/43 (2.3%)
Infections and infestations
NASOPHARYNGITIS	4/43 (9.3%)		6/43 (14%)
URINARY TRACT INFECTION	5/43 (11.6%)		3/43 (7%)
BRONCHITIS	0/43 (0%)		3/43 (7%)
Metabolism and nutrition disorders
ANOREXIA	4/43 (9.3%)		3/43 (7%)
Musculoskeletal and connective tissue disorders
BACK PAIN	5/43 (11.6%)		6/43 (14%)
ARTHRALGIA	1/43 (2.3%)		5/43 (11.6%)
MUSCLE SPASMS	3/43 (7%)		4/43 (9.3%)
Nervous system disorders
DYSGEUSIA	8/43 (18.6%)		5/43 (11.6%)
HEADACHE	1/43 (2.3%)		5/43 (11.6%)
DIZZINESS	3/43 (7%)		3/43 (7%)
HYPOAESTHESIA	0/43 (0%)		3/43 (7%)
PARAESTHESIA	1/43 (2.3%)		3/43 (7%)
PERIPHERAL SENSORY NEUROPATHY	3/43 (7%)		2/43 (4.7%)
Psychiatric disorders
INSOMNIA	8/43 (18.6%)		7/43 (16.3%)
Respiratory, thoracic and mediastinal disorders
DYSPNOEA	1/43 (2.3%)		6/43 (14%)
COUGH	4/43 (9.3%)		4/43 (9.3%)
EPISTAXIS	4/43 (9.3%)		1/43 (2.3%)
DYSPHONIA	3/43 (7%)		1/43 (2.3%)
PHARYNGOLARYNGEAL PAIN	1/43 (2.3%)		3/43 (7%)
Skin and subcutaneous tissue disorders
ALOPECIA	16/43 (37.2%)		19/43 (44.2%)
RASH ERYTHEMATOUS	5/43 (11.6%)		1/43 (2.3%)
ERYTHEMA	4/43 (9.3%)		1/43 (2.3%)
EXFOLIATIVE RASH	4/43 (9.3%)		1/43 (2.3%)
ONYCHOMADESIS	3/43 (7%)		1/43 (2.3%)
PALMAR-PLANTAR ERYTHRODYSAESTHESIA SYNDROME	3/43 (7%)		2/43 (4.7%)
PHOTOSENSITIVITY REACTION	3/43 (7%)		0/43 (0%)
RASH PAPULAR	3/43 (7%)		1/43 (2.3%)
Vascular disorders
HYPERTENSION	6/43 (14%)		1/43 (2.3%)
FLUSHING	3/43 (7%)		1/43 (2.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.