ZACTIMA (an Anti-EGFR / Anti-VEGF Agent) Combined With Docetaxel Compared to Docetaxel in Non-small Cell Lung Cancer
ZODIAC
A Phase III, Randomized, Double-Blinded, Multi-Center, Study to Assess the Efficacy of Docetaxel (TAXOTERE™) in Combination With ZD6474 (ZACTIMA™) Versus Docetaxel (TAXOTERE™) With Placebo in Subjects With Locally Advanced or Metastatic NSCLC
3 other identifiers
interventional
1,690
25 countries
156
Brief Summary
This large phase III clinical study is studying the effect of vandetanib (ZACTIMA) in treating non-small cell lung cancer (NSCLC). Vandetanib is a new type of agent that targets the blood supply to a cancer tumour (through it's anti-vascular endothelial growth factor receptor (VEGFR) properties) and the tumour cells themselves (through it's anti-endothelial growth factor receptor (EGFR) actions). This study will look at the effects of vandetanib in lung cancer patients who have had their cancer re-appear after treatment with standard chemotherapy. This clinical study will test if the vandetanib anti-VEGF and anti-EGFR characteristics can deliver longer improved progression free survival and improved overall survival than docetaxel (Taxotere) alone. All patients participating this clinical study will receive treatment with docetaxel, a commonly used treatment for recurrent non-small cell lung cancer. In addition, some patients will also receive vandetanib (ZACTIMA), an anti-EGFR / anti-VEGF agent. Recent clinical research shows that vascular endothelial growth factor receptor (VEGFR) inhibition, when used with standard chemotherapy, can lead to increased survival in advanced non-small cell lung cancer (NSCLC) patients. Other research shows that epidermal growth factor receptor (EGFR) inhibitors, like erlotinib (Tarceva) can also increase overall non-small cell lung cancer survival by killing tumour cells and stopping them from dividing.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3 nonsmall-cell-lung-cancer
Started May 2006
Longer than P75 for phase_3 nonsmall-cell-lung-cancer
156 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 6, 2006
CompletedFirst Posted
Study publicly available on registry
April 10, 2006
CompletedStudy Start
First participant enrolled
May 1, 2006
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 1, 2008
CompletedResults Posted
Study results publicly available
May 24, 2011
CompletedStudy Completion
Last participant's last visit for all outcomes
March 1, 2014
CompletedSeptember 30, 2016
August 1, 2016
2.3 years
April 6, 2006
April 27, 2011
August 24, 2016
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Progression-Free Survival (PFS) in the Overall Population
Median time (in weeks) from randomisation until objective disease progression or death (by any cause in the absence of objective progression) provided death is within 3 months from the last evaluable RECIST assessment. Progression was derived according to RECIST 1.0 and is defined as an increase of at least 20% in the total tumour size of measurable lesions over the nadir measurement, unequivocal progression in the non-target lesions or the appearance of one or more new lesions.
RECIST tumour assessments carried out every 6 weeks from randomisation until the date of first documented objective disease progression or date of death from any cause, whichever came first assessed up to 24 months
Progression-Free Survival (PFS) in the Female Population
Median time (in weeks) from randomisation until objective disease progression or death (by any cause in the absence of objective progression) provided death is within 3 months from the last evaluable RECIST assessment. Progression was derived according to RECIST 1.0 and is defined as an increase of at least 20% in the total tumour size of measurable lesions over the nadir measurement, unequivocal progression in the non-target lesions or the appearance of one or more new lesions.
RECIST tumour assessments carried out every 6 weeks from randomisation until the date of first documented objective disease progression or date of death from any cause, whichever came first assessed up to 24 months
Secondary Outcomes (7)
Overall Survival (OS) in the Overall Population
Time to death in months
Overall Survival (OS) in the Female Population
Time to death in months
Objective Response Rate (ORR)
Each patient was assessed for objective response from the sequence of RECIST scan data up to data cut off. RECIST tumour assessments carried out every 6 weeks from randomisation until objective progression
Disease Control Rate (DCR)
RECIST tumour assessments carried out every 6 weeks from randomisation until objective progression
Duration of Response (DoR)
RECIST tumour assessments carried out every 6 weeks from randomisation until objective progression
- +2 more secondary outcomes
Study Arms (2)
1
ACTIVE COMPARATORDocetaxel monotherapy
2
EXPERIMENTALVandetanib + Docetaxel
Interventions
Eligibility Criteria
You may qualify if:
- Lung cancer patients who answer true to the following statements are eligible to join this clinical study.
- I have a confirmed diagnosis of locally advanced or metastatic non small cell lung cancer (Stage IIIb - IV)
- I have had 1st line anti-cancer therapy. Previous treatment with Avastin (bevacizumab) in first line NSCLC is allowed.
You may not qualify if:
- Lung cancer patients who answer true to the following are NOT eligible to join this clinical study.
- I do not have non small cell lung cancer (NSCLC)
- I have received treatment with docetaxel (Taxotere). Prior treatment with paclitaxel is acceptable.
- I have received 2nd line anti-cancer therapy (For example, patients with previous 2nd line non small cell lung cancer (NSCLC) treatment with Tarceva (erlotinib, OSI-744), Alimta (pemetrexed) are not eligible)
- I have been treated with VEGFR-tyrosine kinase inhibitors (TKIs) (sunitinib, sorafenib, other VEGF TKIs). Previous treatment with Avastin (bevacizumab) in 1st line non small cell lung cancer is permitted.
- I have a history of uncontrolled irregular heartbeat
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (156)
Research Site
Fullerton, California, United States
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Los Angeles, California, United States
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Northridge, California, United States
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Colorado Springs, Colorado, United States
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Norwalk, Connecticut, United States
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Ocala, Florida, United States
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Marietta, Georgia, United States
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Joliet, Illinois, United States
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Park Ridge, Illinois, United States
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Hutchinson, Kansas, United States
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Louisville, Kentucky, United States
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Boston, Massachusetts, United States
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Ann Arbor, Michigan, United States
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St Louis, Missouri, United States
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Henderson, Nevada, United States
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Albany, New York, United States
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Armonk, New York, United States
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New York, New York, United States
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Durham, North Carolina, United States
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Hickory, North Carolina, United States
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Portland, Oregon, United States
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Austin, Texas, United States
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Houston, Texas, United States
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Ogden, Utah, United States
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Alexandria, Virginia, United States
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Salem, Virginia, United States
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Vancouver, Washington, United States
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Bahía Blanca, Argentina
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Capital Federal, Argentina
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Ciudad de Buenos Aires, Argentina
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Mendoza, Argentina
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Rosario, Argentina
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Graz, Austria
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Grimmenstein, Austria
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Innsbruck, Austria
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Linz, Austria
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Vienna, Austria
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Wels, Austria
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Brussels (Jette), Belgium
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Brussels (Woluwé-St-Lambert), Belgium
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Edegem, Belgium
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Genk, Belgium
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Liège, Belgium
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Fortaleza, Brazil
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Goiânia, Brazil
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Porto Alegre, Brazil
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Rio de Janeiro, Brazil
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São Paulo, Brazil
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Edmonton, Alberta, Canada
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Moncton, New Brunswick, Canada
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Halifax, Nova Scotia, Canada
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Kitchener, Ontario, Canada
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London, Ontario, Canada
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Toronto, Ontario, Canada
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Laval, Quebec, Canada
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Québec, Quebec, Canada
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Beijing, China
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Chongqing, China
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Guangzhou, China
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Nanjing, China
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Shanghai, China
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Wuhan, China
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Herlev, Denmark
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København Ø, Denmark
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Odense, Denmark
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Roskilde, Denmark
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Vejle, Denmark
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Bordeaux, France
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Boulogne-Billancourt, France
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Caen, France
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Dijon, France
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Nancy, France
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Paris, France
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Pierre-Bénite, France
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Saint-Herblain, France
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Bad Berka, Germany
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Berlin, Germany
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Cologne, Germany
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Essen, Germany
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Großhansdorf, Germany
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Halle, Germany
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Hamburg, Germany
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Heidelberg, Germany
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Oldenburg, Germany
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Ulm, Germany
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Wiesbaden, Germany
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Athens, Greece
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Heraklion, Greece
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Ahmedabad, India
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Chennai, India
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Hyderabad, India
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Kolkata, India
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New Delhi, India
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Pune, India
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Vellore, India
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Jakarta Timur, Indonesia
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Yogyakarta, Indonesia
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Ancona, Italy
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Avellino, Italy
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Bologna, Italy
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Genova, Italy
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Mantova, Italy
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Napoli, Italy
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Orbassano, Italy
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Parma, Italy
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Perugia, Italy
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Pisa, Italy
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Reggio Emilia, Italy
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Akashi-shi, Japan
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Fukuoka, Japan
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Isehara-shi, Japan
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Kobe, Japan
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Kōtoku, Japan
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Kumamoto, Japan
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Matsuyama, Japan
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Nagoya, Japan
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Okayama, Japan
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Okazaki-shi, Japan
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Osaka, Japan
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Osakasayama-shi, Japan
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Sakaishi, Japan
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Sapporo, Japan
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Shinjuku-ku, Japan
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Sunto-gun, Japan
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Toyonaka, Japan
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Ube-shi, Japan
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Utsunomiya, Japan
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Yokohama, Japan
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George Town, Malaysia
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Kampung Baharu Nilai, Malaysia
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Kubang Kerian, Malaysia
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Durango, Mexico
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Morelia, Mexico
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Toluca, Mexico
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's-Hertogenbosch, Netherlands
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Amsterdam, Netherlands
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Groningen, Netherlands
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Maastricht, Netherlands
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Coimbra, Portugal
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Funchal, Portugal
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Lisbon, Portugal
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Porto, Portugal
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Vila Nova de Gaia, Portugal
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Singapore, Singapore
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Seoul, South Korea
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A Coruña, Spain
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Alicante, Spain
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Madrid, Spain
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Málaga, Spain
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Zaragoza, Spain
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Chiang Mai, Thailand
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Ankara, Turkey (Türkiye)
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Istanbul, Turkey (Türkiye)
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Izmir, Turkey (Türkiye)
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Hanoi, Vietnam
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Ho Chi Minh City, Vietnam
Related Publications (4)
Lombard A, Mistry H, Aarons L, Ogungbenro K. Dose individualisation in oncology using chemotherapy-induced neutropenia: Example of docetaxel in non-small cell lung cancer patients. Br J Clin Pharmacol. 2021 Apr;87(4):2053-2063. doi: 10.1111/bcp.14614. Epub 2020 Dec 19.
PMID: 33075149DERIVEDPlatt A, Morten J, Ji Q, Elvin P, Womack C, Su X, Donald E, Gray N, Read J, Bigley G, Blockley L, Cresswell C, Dale A, Davies A, Zhang T, Fan S, Fu H, Gladwin A, Harrod G, Stevens J, Williams V, Ye Q, Zheng L, de Boer R, Herbst RS, Lee JS, Vasselli J. A retrospective analysis of RET translocation, gene copy number gain and expression in NSCLC patients treated with vandetanib in four randomized Phase III studies. BMC Cancer. 2015 Mar 23;15:171. doi: 10.1186/s12885-015-1146-8.
PMID: 25881079DERIVEDHeymach JV, Lockwood SJ, Herbst RS, Johnson BE, Ryan AJ. EGFR biomarkers predict benefit from vandetanib in combination with docetaxel in a randomized phase III study of second-line treatment of patients with advanced non-small cell lung cancer. Ann Oncol. 2014 Oct;25(10):1941-1948. doi: 10.1093/annonc/mdu269. Epub 2014 Jul 23.
PMID: 25057173DERIVEDHerbst RS, Sun Y, Eberhardt WE, Germonpre P, Saijo N, Zhou C, Wang J, Li L, Kabbinavar F, Ichinose Y, Qin S, Zhang L, Biesma B, Heymach JV, Langmuir P, Kennedy SJ, Tada H, Johnson BE. Vandetanib plus docetaxel versus docetaxel as second-line treatment for patients with advanced non-small-cell lung cancer (ZODIAC): a double-blind, randomised, phase 3 trial. Lancet Oncol. 2010 Jul;11(7):619-26. doi: 10.1016/S1470-2045(10)70132-7.
PMID: 20570559DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Trial Transparency Team
- Organization
- Sanofi
Study Officials
- STUDY DIRECTOR
Contact-US@sanofi.com
Sanofi
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 6, 2006
First Posted
April 10, 2006
Study Start
May 1, 2006
Primary Completion
August 1, 2008
Study Completion
March 1, 2014
Last Updated
September 30, 2016
Results First Posted
May 24, 2011
Record last verified: 2016-08