A Phase II Study of 2 Doses of ZD6474 (Vandetanib) in Combination With FOLFOX vs FOLFOX Alone for the Treatment of Colorectal Cancer

• Sponsor: Genzyme, a Sanofi Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00500292
• Collaborator: (none)
• Enrollment: 109
• Locations: 15
• Arms: 3
• Duration (Months): 116.1
• Patients Per Site: 7.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether treatment with ZACTIMA (vandetanib) in combination with FOLFOX is more effective than FOLFOX alone for colorectal cancer in patients who have failed therapy with an irinotecan and fluoropyrimidine containing regimen.

Condition or Disease	Intervention/Treatment	Phase
Colorectal; Cancer	Drug: Vandetanib; Drug: FOLFOX regimen=oxaliplatin, fluorouracil, & folinic acid	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 109 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 2 Doses of ZD6474 (Vandetanib) in Combination With FOLFOX vs FOLFOX Alone for the Treatment of Colorectal Cancer in Patients Who Have Failed Therapy With an Irinotecan and Fluoropyrimidine Regimen
• Study Start Date: Mar 1, 2007
• Actual Primary Completion Date: Mar 1, 2008
• Actual Study Completion Date: Nov 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: 1 FOLFOX + Placebo vandetanib	Drug: FOLFOX regimen=oxaliplatin, fluorouracil, & folinic acid; intravenous infusion
Experimental: 2 FOLFOX + low dose vandetanib	Drug: Vandetanib; once daily oral tablet two dose strengths; Other Names: AZ6474 ZACTIMA™ SAR390530 ; Drug: FOLFOX regimen=oxaliplatin, fluorouracil, & folinic acid; intravenous infusion
Experimental: 3 FOLFOX + high dose vandetanib	Drug: Vandetanib; once daily oral tablet two dose strengths; Other Names: AZ6474 ZACTIMA™ SAR390530 ; Drug: FOLFOX regimen=oxaliplatin, fluorouracil, & folinic acid; intravenous infusion

Outcome Measures

Primary 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 (5 March 2008 +/-3 days)]

   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: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Progression on or following treatment for metastatic colorectal cancer

• Have failed therapy with an irinotecan and fluoropyrimidine containing regimen

• Have World Health Organisation (WHO) performance status 0-2 and life expectancy >12 weeks

Exclusion Criteria:

• Previous treatment with small molecule tyrosine kinase inhibitors of VEGFR or EGFR Prior monoclonal antibodies are permitted, (eg, cetuximab, bevacizumab)

• Previous adjuvant therapy with irinotecan within 12 months of randomisation

• More than one prior course of chemotherapy for treatment of metastatic colorectal cancer

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Lille Cedex		France
2	Research Site	Toulouse Cedex 9		France
3	Research Site	Budapest		Hungary
4	Research Site	Debrecen		Hungary
5	Research Site	Szeged		Hungary
6	Research Site	Seoul		Korea, Republic of
7	Research Site	Bratislava		Slovakia
8	Research Site	Poprad		Slovakia
9	Research Site	Trnava		Slovakia
10	Research Site	Zilina		Slovakia
11	Research Site	Hospitalet deLlobregat		Spain
12	Research Site	Oviedo		Spain
13	Research Site	Santander		Spain
14	Research Site	Taipei		Taiwan
15	Research Site	Tao-Yuan		Taiwan

Sponsors and Collaborators

• Genzyme, a Sanofi Company

Investigators

• Study Director: Clinical Sciences & Operations, Sanofi

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info
• CSR-D4200C00047.pdf

Publications

None provided.

• Responsible Party: Genzyme, a Sanofi Company
• ClinicalTrials.gov Identifier: NCT00500292
• Other Study ID Numbers: D4200C00047; 2006-005022-23; LPS15025
• First Posted: Jul 12, 2007
• Last Update Posted: Jan 25, 2018
• Last Verified: Jan 1, 2018

• Keywords provided by Genzyme, a Sanofi Company: colorectal; cancer; zactima
• Additional relevant MeSH terms: Colorectal Neoplasms; Leucovorin; Folic Acid; Fluorouracil; Oxaliplatin; Levoleucovorin

Study Results

Participant Flow

Recruitment Details	First patient randomised 19 March 2007, last patient randomised 11 Nov 2007, data cut off date 8 March 2008. 109 patients were enrolled in the study.
Pre-assignment Detail	109 patients were enrolled/screened to the study but only 104 patients were entered treatment/randomized.

Arm/Group Title	Vandetanib 100 mg Plus FOLFOX	Vandetanib 300 mg Plus FOLFOX	Placebo Plus FOLFOX
Arm/Group Description	vandetanib 100 mg plus FOLFOX	vandetanib 300 mg plus FOLFOX	placebo plus FOLFOX
Period Title: Overall Study
STARTED	32	35	37
COMPLETED	7	4	10
NOT COMPLETED	25	31	27

Baseline Characteristics

Arm/Group Title	Vandetanib 100 mg Plus FOLFOX	Vandetanib 300 mg Plus FOLFOX	Placebo Plus FOLFOX	Total
Arm/Group Description	vandetanib 100 mg plus FOLFOX	vandetanib 300 mg plus FOLFOX	placebo plus FOLFOX	Total of all reporting groups
Overall Participants	32	35	37	104
Age (Years) [Mean (Full Range) ]
Mean (Full Range) [Years]	57	58	59	58
Sex: Female, Male (Count of Participants)
Female	16 50%	11 31.4%	13 35.1%	40 38.5%
Male	16 50%	24 68.6%	24 64.9%	64 61.5%

Outcome Measures

1. Primary 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 (5 March 2008 +/-3 days)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vandetanib 100 mg Plus FOLFOX	Vandetanib 300 mg Plus FOLFOX	Placebo Plus FOLFOX
Arm/Group Description	vandetanib 100 mg plus FOLFOX	vandetanib 300 mg plus FOLFOX	placebo plus FOLFOX
Measure Participants	32	35	37
Number [Participants]	23 71.9%	27 77.1%	24 64.9%

Adverse Events

Arm/Group Title	Vandetanib 100 mg		Vandetanib 300 mg		Placebo
Arm/Group Description	vandetanib 100 mg plus FOLFOX		vandetanib 300 mg plus FOLFOX		placebo plus FOLFOX
All Cause Mortality
	Vandetanib 100 mg		Vandetanib 300 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Vandetanib 100 mg		Vandetanib 300 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/32 (18.8%)		10/35 (28.6%)		4/37 (10.8%)
Cardiac disorders
Angina Pectoris	0/32 (0%)		0/35 (0%)		1/37 (2.7%)
Gastrointestinal disorders
Diarrhoea	0/32 (0%)		1/35 (2.9%)		0/37 (0%)
Ileus	0/32 (0%)		1/35 (2.9%)		0/37 (0%)
Intestinal Obstruction	0/32 (0%)		0/35 (0%)		1/37 (2.7%)
Subileus	0/32 (0%)		1/35 (2.9%)		0/37 (0%)
Vomiting	0/32 (0%)		0/35 (0%)		1/37 (2.7%)
General disorders
Mucosal Inflammation	0/32 (0%)		1/35 (2.9%)		0/37 (0%)
Pyrexia	0/32 (0%)		1/35 (2.9%)		1/37 (2.7%)
Immune system disorders
Anaphylactic Reaction	0/32 (0%)		0/35 (0%)		1/37 (2.7%)
Infections and infestations
Appendicitis	0/32 (0%)		1/35 (2.9%)		0/37 (0%)
Device Related Infection	2/32 (6.3%)		0/35 (0%)		0/37 (0%)
Lung Abscess	0/32 (0%)		1/35 (2.9%)		0/37 (0%)
Pneumonia	1/32 (3.1%)		3/35 (8.6%)		0/37 (0%)
Staphylococcal Infection	0/32 (0%)		1/35 (2.9%)		0/37 (0%)
Staphylococcal Sepsis	0/32 (0%)		1/35 (2.9%)		0/37 (0%)
Injury, poisoning and procedural complications
Contusion	1/32 (3.1%)		0/35 (0%)		0/37 (0%)
Metabolism and nutrition disorders
Decreased Appetite	0/32 (0%)		1/35 (2.9%)		0/37 (0%)
Hypomagnesaemia	0/32 (0%)		1/35 (2.9%)		0/37 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma Gastric	1/32 (3.1%)		0/35 (0%)		0/37 (0%)
Nervous system disorders
Haemorrhage Intracranial	0/32 (0%)		1/35 (2.9%)		0/37 (0%)
Reproductive system and breast disorders
Female Genital Tract Fistula	1/32 (3.1%)		0/35 (0%)		0/37 (0%)
Skin and subcutaneous tissue disorders
Toxic Epidermal Necrolysis	0/32 (0%)		1/35 (2.9%)		0/37 (0%)
Vascular disorders
Hypertension	1/32 (3.1%)		0/35 (0%)		0/37 (0%)
Venous Thrombosis	1/32 (3.1%)		0/35 (0%)		0/37 (0%)
Other (Not Including Serious) Adverse Events
	Vandetanib 100 mg		Vandetanib 300 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	31/32 (96.9%)		32/35 (91.4%)		35/37 (94.6%)
Blood and lymphatic system disorders
Leukopenia	4/32 (12.5%)		5/35 (14.3%)		5/37 (13.5%)
Neutropenia	13/32 (40.6%)		11/35 (31.4%)		13/37 (35.1%)
Thrombocytopenia	16/32 (50%)		18/35 (51.4%)		13/37 (35.1%)
Cardiac disorders
Tachycardia	0/32 (0%)		0/35 (0%)		2/37 (5.4%)
Eye disorders
Vision Blurred	0/32 (0%)		2/35 (5.7%)		1/37 (2.7%)
Gastrointestinal disorders
Abdominal Distension	2/32 (6.3%)		3/35 (8.6%)		2/37 (5.4%)
Abdominal Pain	2/32 (6.3%)		3/35 (8.6%)		10/37 (27%)
Abdominal Pain Upper	2/32 (6.3%)		1/35 (2.9%)		4/37 (10.8%)
Constipation	6/32 (18.8%)		3/35 (8.6%)		6/37 (16.2%)
Diarrhoea	16/32 (50%)		22/35 (62.9%)		16/37 (43.2%)
Epigastric Discomfort	0/32 (0%)		2/35 (5.7%)		0/37 (0%)
Flatulence	0/32 (0%)		0/35 (0%)		2/37 (5.4%)
Gingival Bleeding	0/32 (0%)		2/35 (5.7%)		0/37 (0%)
Nausea	13/32 (40.6%)		15/35 (42.9%)		24/37 (64.9%)
Rectal Haemorrhage	0/32 (0%)		0/35 (0%)		2/37 (5.4%)
Stomatitis	8/32 (25%)		11/35 (31.4%)		10/37 (27%)
Toothache	0/32 (0%)		1/35 (2.9%)		2/37 (5.4%)
Vomiting	9/32 (28.1%)		5/35 (14.3%)		14/37 (37.8%)
General disorders
Asthenia	4/32 (12.5%)		8/35 (22.9%)		6/37 (16.2%)
Chills	1/32 (3.1%)		1/35 (2.9%)		2/37 (5.4%)
Fatigue	8/32 (25%)		10/35 (28.6%)		15/37 (40.5%)
Oedema Peripheral	1/32 (3.1%)		2/35 (5.7%)		1/37 (2.7%)
Pyrexia	3/32 (9.4%)		5/35 (14.3%)		9/37 (24.3%)
Hepatobiliary disorders
Hepatotoxicity	0/32 (0%)		2/35 (5.7%)		0/37 (0%)
Hyperbilirubinaemia	0/32 (0%)		0/35 (0%)		2/37 (5.4%)
Immune system disorders
Drug Hypersensitivity	3/32 (9.4%)		4/35 (11.4%)		5/37 (13.5%)
Infections and infestations
Bronchitis	0/32 (0%)		2/35 (5.7%)		1/37 (2.7%)
Nasopharyngitis	4/32 (12.5%)		1/35 (2.9%)		2/37 (5.4%)
Pharyngitis	2/32 (6.3%)		1/35 (2.9%)		0/37 (0%)
Investigations
Electrocardiogram Qt Prolonged	1/32 (3.1%)		6/35 (17.1%)		1/37 (2.7%)
Weight Decreased	3/32 (9.4%)		1/35 (2.9%)		2/37 (5.4%)
Metabolism and nutrition disorders
Anorexia	10/32 (31.3%)		11/35 (31.4%)		9/37 (24.3%)
Decreased Appetite	0/32 (0%)		0/35 (0%)		2/37 (5.4%)
Musculoskeletal and connective tissue disorders
Back Pain	5/32 (15.6%)		4/35 (11.4%)		4/37 (10.8%)
Musculoskeletal Pain	2/32 (6.3%)		0/35 (0%)		1/37 (2.7%)
Nervous system disorders
Dizziness	2/32 (6.3%)		2/35 (5.7%)		3/37 (8.1%)
Dysaesthesia	1/32 (3.1%)		1/35 (2.9%)		3/37 (8.1%)
Dysgeusia	0/32 (0%)		0/35 (0%)		2/37 (5.4%)
Headache	2/32 (6.3%)		5/35 (14.3%)		2/37 (5.4%)
Lethargy	2/32 (6.3%)		0/35 (0%)		1/37 (2.7%)
Paraesthesia	4/32 (12.5%)		5/35 (14.3%)		3/37 (8.1%)
Peripheral Sensory Neuropathy	16/32 (50%)		12/35 (34.3%)		18/37 (48.6%)
Psychiatric disorders
Anxiety	0/32 (0%)		3/35 (8.6%)		0/37 (0%)
Confusional State	0/32 (0%)		2/35 (5.7%)		0/37 (0%)
Insomnia	3/32 (9.4%)		3/35 (8.6%)		3/37 (8.1%)
Renal and urinary disorders
Dysuria	0/32 (0%)		2/35 (5.7%)		1/37 (2.7%)
Haematuria	0/32 (0%)		2/35 (5.7%)		0/37 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	6/32 (18.8%)		1/35 (2.9%)		3/37 (8.1%)
Dyspnoea	3/32 (9.4%)		4/35 (11.4%)		2/37 (5.4%)
Epistaxis	2/32 (6.3%)		3/35 (8.6%)		4/37 (10.8%)
Pharyngolaryngeal Pain	2/32 (6.3%)		1/35 (2.9%)		0/37 (0%)
Skin and subcutaneous tissue disorders
Acne	3/32 (9.4%)		2/35 (5.7%)		3/37 (8.1%)
Alopecia	3/32 (9.4%)		1/35 (2.9%)		3/37 (8.1%)
Dermatitis Acneiform	1/32 (3.1%)		5/35 (14.3%)		1/37 (2.7%)
Dry Skin	2/32 (6.3%)		2/35 (5.7%)		1/37 (2.7%)
Hyperhidrosis	0/32 (0%)		2/35 (5.7%)		0/37 (0%)
Palmar-Plantar Erythrodysaesthesia Syndrome	3/32 (9.4%)		3/35 (8.6%)		1/37 (2.7%)
Photosensitivity Reaction	3/32 (9.4%)		7/35 (20%)		1/37 (2.7%)
Pigmentation Disorder	1/32 (3.1%)		2/35 (5.7%)		1/37 (2.7%)
Pruritus	1/32 (3.1%)		2/35 (5.7%)		3/37 (8.1%)
Rash	7/32 (21.9%)		7/35 (20%)		3/37 (8.1%)
Urticaria	1/32 (3.1%)		0/35 (0%)		2/37 (5.4%)
Vascular disorders
Hypertension	13/32 (40.6%)		13/35 (37.1%)		5/37 (13.5%)
Phlebitis	2/32 (6.3%)		1/35 (2.9%)		1/37 (2.7%)
Phlebitis Superficial	2/32 (6.3%)		1/35 (2.9%)		0/37 (0%)

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.