E3 Breast Cancer Taxotere Combination

• Sponsor: Genzyme, a Sanofi Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00494481
• Collaborator: (none)
• Enrollment: 64
• Locations: 12
• Arms: 2
• Duration (Months): 36
• Patients Per Site: 5.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

To assess the efficacy of ZD6474 in combination with docetaxel in the treatment of ABC using the progression event count methodology

Condition or Disease	Intervention/Treatment	Phase
Advanced Breast Cancer	Drug: Vandetanib (ZD6474); Drug: Docetaxel	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 64 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase II, Double-blind, Placebo Controlled, Randomized Study to Assess the Efficacy and Safety of ZD6474 in Combination With Docetaxel (Taxotere™) vs Docetaxel Alone as 2nd Line Treatment for Advanced Breast Cancer (ABC).
• Study Start Date: Jan 1, 2006
• Actual Primary Completion Date: Jun 1, 2007
• Actual Study Completion Date: Jan 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: 1 Docetaxel + placebo vandetanib	Drug: Docetaxel; intravenous infusion; Other Names: Taxotere®
Experimental: 2 Vandetanib + Docetaxel	Drug: Vandetanib (ZD6474); once daily oral dose; Other Names: ZACTIMA™ ; Drug: Docetaxel; intravenous infusion; Other Names: Taxotere®

Outcome Measures

Primary Outcome Measures

1. Number of Patients With a Disease Progression Event [RECIST tumour assessments carried out at screening (within 3 weeks before the 1st dose) and then as per site clinical practice until objective progression. The only additional mandatory RECIST assessment is at the point of data cut-off]

   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: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Females with histological/cytological confirmation of breast cancer.

• Subjects with a measurable lesion or bone lesions

Exclusion Criteria:

• Previous radiotherapy within 6 weeks

• Significant cardiac events, arrhythmias or other cardiac conditions

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Budapest		Hungary
2	Research Site	Pécs		Hungary
3	Research SIte	Bloemfontein		South Africa
4	Research Site	Cape Town		South Africa
5	Research Site	Observatory		South Africa
6	Research Site	Baracaldo		Spain
7	Research SIte	Lérida		Spain
8	Research Site	Zaragoza		Spain
9	Research Site	Umeå		Sweden
10	Research Site	Uppsala		Sweden
11	Research Site	Västerås		Sweden
12	Research Site	Taipei		Taiwan

Sponsors and Collaborators

• Genzyme, a Sanofi Company

Investigators

• Study Director: Clinical Sciences & Operations, Sanofi

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Genzyme, a Sanofi Company
• ClinicalTrials.gov Identifier: NCT00494481
• Other Study ID Numbers: D4200C00046; 2005-003592-20
• First Posted: Jun 29, 2007
• Last Update Posted: Sep 30, 2016
• Last Verified: Aug 1, 2016

• Keywords provided by Genzyme, a Sanofi Company: Zactima
• Additional relevant MeSH terms: Breast Neoplasms; Docetaxel

Study Results

Participant Flow

Recruitment Details	First patient randomised 03 February 2006, last patient randomised 25 April 2007, data cut off data 23 June 2007

Arm/Group Title	Vandetanib Plus Docetaxel	Placebo Plus Docetaxel
Arm/Group Description	vandetanib 100 mg plus docetaxel	placebo plus docetaxel
Period Title: Overall Study
STARTED	35	29
COMPLETED	6	5
NOT COMPLETED	29	24

Baseline Characteristics

Arm/Group Title	Vandetanib Plus Docetaxel	Placebo Plus Docetaxel	Total
Arm/Group Description	vandetanib 100 mg plus docetaxel	placebo plus docetaxel	Total of all reporting groups
Overall Participants	35	29	64
Age (Years) [Mean (Full Range) ]
Mean (Full Range) [Years]	54	57	55.5
Sex: Female, Male (Count of Participants)
Female	35 100%	29 100%	64 100%
Male	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Number of Patients With a 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 (within 3 weeks before the 1st dose) and then as per site clinical practice until objective progression. The only additional mandatory RECIST assessment is at the point of data cut-off

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vandetanib Plus Docetaxel	Placebo Plus Docetaxel
Arm/Group Description	vandetanib 100 mg plus docetaxel	placebo plus docetaxel
Measure Participants	35	29
Number [Participants]	24 68.6%	18 62.1%

Adverse Events

Arm/Group Title	Vandetanib Plus Docetaxel		Placebo Plus Docetaxel
Arm/Group Description	vandetanib 100 mg plus docetaxel		placebo plus docetaxel
All Cause Mortality
	Vandetanib Plus Docetaxel		Placebo Plus Docetaxel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Vandetanib Plus Docetaxel		Placebo Plus Docetaxel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/33 (42.4%)		12/29 (41.4%)
Blood and lymphatic system disorders
Neutropenia	4/33 (12.1%)		2/29 (6.9%)
Febrile Neutropenia	3/33 (9.1%)		1/29 (3.4%)
Granulocytopenia	0/33 (0%)		1/29 (3.4%)
Cardiac disorders
Atrial Fibrillation	1/33 (3%)		1/29 (3.4%)
Ear and labyrinth disorders
Vertigo	1/33 (3%)		0/29 (0%)
Eye disorders
Keratitis	1/33 (3%)		0/29 (0%)
Gastrointestinal disorders
Diarrhoea	3/33 (9.1%)		0/29 (0%)
Colitis	0/33 (0%)		1/29 (3.4%)
Ileus	1/33 (3%)		0/29 (0%)
Nausea	1/33 (3%)		0/29 (0%)
Stomatitis	1/33 (3%)		0/29 (0%)
General disorders
Asthenia	1/33 (3%)		0/29 (0%)
Fatigue	1/33 (3%)		0/29 (0%)
Pyrexia	0/33 (0%)		1/29 (3.4%)
Infections and infestations
Neutropenic Sepsis	0/33 (0%)		2/29 (6.9%)
Cellulitis	1/33 (3%)		0/29 (0%)
Pharyngitis Streptococcal	0/33 (0%)		1/29 (3.4%)
Pneumonia	1/33 (3%)		1/29 (3.4%)
Tooth Abscess	0/33 (0%)		1/29 (3.4%)
Metabolism and nutrition disorders
Hypokalaemia	1/33 (3%)		0/29 (0%)
Nervous system disorders
Vocal Cord Paralysis	0/33 (0%)		1/29 (3.4%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	0/33 (0%)		3/29 (10.3%)
Hydrothorax	0/33 (0%)		1/29 (3.4%)
Skin and subcutaneous tissue disorders
Dermatitis Exfoliative	1/33 (3%)		0/29 (0%)
Rash Papular	1/33 (3%)		0/29 (0%)
Toxic Epidermal Necrolysis	1/33 (3%)		0/29 (0%)
Vascular disorders
Deep Vein Thrombosis	0/33 (0%)		1/29 (3.4%)
Hypertension	1/33 (3%)		0/29 (0%)
Other (Not Including Serious) Adverse Events
	Vandetanib Plus Docetaxel		Placebo Plus Docetaxel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	33/33 (100%)		25/29 (86.2%)
Blood and lymphatic system disorders
Neutropenia	15/33 (45.5%)		13/29 (44.8%)
Leukopenia	10/33 (30.3%)		8/29 (27.6%)
Anaemia	6/33 (18.2%)		6/29 (20.7%)
Thrombocytopenia	4/33 (12.1%)		0/29 (0%)
Febrile Neutropenia	3/33 (9.1%)		0/29 (0%)
Lymphopenia	3/33 (9.1%)		2/29 (6.9%)
Agranulocytosis	2/33 (6.1%)		2/29 (6.9%)
Ear and labyrinth disorders
Vertigo	2/33 (6.1%)		1/29 (3.4%)
Eye disorders
Lacrimation Increased	2/33 (6.1%)		7/29 (24.1%)
Conjunctivitis	2/33 (6.1%)		3/29 (10.3%)
Vision Blurred	0/33 (0%)		2/29 (6.9%)
Gastrointestinal disorders
Stomatitis	16/33 (48.5%)		12/29 (41.4%)
Diarrhoea	13/33 (39.4%)		12/29 (41.4%)
Nausea	9/33 (27.3%)		10/29 (34.5%)
Abdominal Pain	6/33 (18.2%)		5/29 (17.2%)
Vomiting	3/33 (9.1%)		6/29 (20.7%)
Constipation	5/33 (15.2%)		2/29 (6.9%)
Dry Mouth	4/33 (12.1%)		1/29 (3.4%)
Cheilitis	1/33 (3%)		3/29 (10.3%)
Dyspepsia	3/33 (9.1%)		3/29 (10.3%)
Flatulence	2/33 (6.1%)		1/29 (3.4%)
Gastritis	2/33 (6.1%)		2/29 (6.9%)
Mouth Ulceration	0/33 (0%)		2/29 (6.9%)
Odynophagia	2/33 (6.1%)		0/29 (0%)
General disorders
Fatigue	11/33 (33.3%)		7/29 (24.1%)
Asthenia	3/33 (9.1%)		8/29 (27.6%)
Oedema Peripheral	7/33 (21.2%)		6/29 (20.7%)
Pyrexia	5/33 (15.2%)		3/29 (10.3%)
Face Oedema	1/33 (3%)		2/29 (6.9%)
Influenza Like Illness	1/33 (3%)		2/29 (6.9%)
Malaise	2/33 (6.1%)		0/29 (0%)
Performance Status Decreased	2/33 (6.1%)		0/29 (0%)
Infections and infestations
Pharyngitis	2/33 (6.1%)		3/29 (10.3%)
Upper Respiratory Tract Infection	0/33 (0%)		3/29 (10.3%)
Herpes Zoster	0/33 (0%)		2/29 (6.9%)
Nasopharyngitis	2/33 (6.1%)		1/29 (3.4%)
Oral Candidiasis	1/33 (3%)		2/29 (6.9%)
Urinary Tract Infection	2/33 (6.1%)		0/29 (0%)
Injury, poisoning and procedural complications
Chemical Eye Injury	2/33 (6.1%)		2/29 (6.9%)
Weight Decreased	3/33 (9.1%)		2/29 (6.9%)
Alanine Aminotransferase Increased	2/33 (6.1%)		2/29 (6.9%)
Aspartate Aminotransferase Increased	2/33 (6.1%)		2/29 (6.9%)
Blood Alkaline Phosphatase Increased	2/33 (6.1%)		1/29 (3.4%)
Metabolism and nutrition disorders
Anorexia	7/33 (21.2%)		9/29 (31%)
Musculoskeletal and connective tissue disorders
Myalgia	10/33 (30.3%)		9/29 (31%)
Bone Pain	0/33 (0%)		4/29 (13.8%)
Arthralgia	3/33 (9.1%)		2/29 (6.9%)
Pain In Extremity	2/33 (6.1%)		3/29 (10.3%)
Back Pain	1/33 (3%)		2/29 (6.9%)
Musculoskeletal Chest Pain	2/33 (6.1%)		0/29 (0%)
Musculoskeletal Pain	1/33 (3%)		2/29 (6.9%)
Nervous system disorders
Paraesthesia	4/33 (12.1%)		9/29 (31%)
Peripheral Sensory Neuropathy	6/33 (18.2%)		3/29 (10.3%)
Dysgeusia	5/33 (15.2%)		4/29 (13.8%)
Headache	4/33 (12.1%)		4/29 (13.8%)
Hypoaesthesia	4/33 (12.1%)		3/29 (10.3%)
Dizziness	3/33 (9.1%)		2/29 (6.9%)
Lethargy	3/33 (9.1%)		3/29 (10.3%)
Neurotoxicity	2/33 (6.1%)		1/29 (3.4%)
Psychiatric disorders
Insomnia	3/33 (9.1%)		2/29 (6.9%)
Depression	2/33 (6.1%)		1/29 (3.4%)
Renal and urinary disorders
Dysuria	2/33 (6.1%)		1/29 (3.4%)
Reproductive system and breast disorders
Vaginal Discharge	0/33 (0%)		2/29 (6.9%)
Respiratory, thoracic and mediastinal disorders
Cough	8/33 (24.2%)		3/29 (10.3%)
Dyspnoea	6/33 (18.2%)		4/29 (13.8%)
Pharyngolaryngeal Pain	5/33 (15.2%)		1/29 (3.4%)
Epistaxis	4/33 (12.1%)		0/29 (0%)
Rhinorrhoea	2/33 (6.1%)		1/29 (3.4%)
Skin and subcutaneous tissue disorders
Alopecia	17/33 (51.5%)		11/29 (37.9%)
Erythema	7/33 (21.2%)		4/29 (13.8%)
Onycholysis	6/33 (18.2%)		1/29 (3.4%)
Dry Skin	5/33 (15.2%)		5/29 (17.2%)
Rash Maculo-Papular	5/33 (15.2%)		0/29 (0%)
Skin Exfoliation	2/33 (6.1%)		5/29 (17.2%)
Dermatitis Acneiform	3/33 (9.1%)		4/29 (13.8%)
Acne	3/33 (9.1%)		1/29 (3.4%)
Nail Discolouration	3/33 (9.1%)		0/29 (0%)
Nail Pigmentation	3/33 (9.1%)		3/29 (10.3%)
Palmar-Plantar Erythrodysaesthesia Syndrome	3/33 (9.1%)		0/29 (0%)
Rash Erythematous	1/33 (3%)		3/29 (10.3%)
Skin Hyperpigmentation	3/33 (9.1%)		3/29 (10.3%)
Nail Disorder	2/33 (6.1%)		2/29 (6.9%)
Pigmentation Disorder	2/33 (6.1%)		0/29 (0%)
Rash	2/33 (6.1%)		1/29 (3.4%)
Rash Pruritic	2/33 (6.1%)		0/29 (0%)
Vascular disorders
Hypertension	5/33 (15.2%)		0/29 (0%)
Flushing	2/33 (6.1%)		2/29 (6.9%)
Hot Flush	0/33 (0%)		2/29 (6.9%)
Lymphoedema	0/33 (0%)		2/29 (6.9%)

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.