Clinical trial NCT00312377: ZACTIMA (an Anti-EGFR / Anti-VEGF Agent) Combined With Docetaxel Compared to Docetaxel in Non-small Cell Lung Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Non-small Cell Lung Cancer
Lung Cancer
Keywords: Non-small cell lung cancer
NSCLC
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2006-04-10
Enrollment: 1690
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

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.

Exclusion Criteria:

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
* I have a history of high blood pressure which has not been controlled with medication If you are unsure of the meaning of the inclusion and exclusion criteria above, please contact the call center number for help.

Primary outcomes:
measure: Progression-Free Survival (PFS) in the Overall Population
timeFrame: 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
measure: Progression-Free Survival (PFS) in the Female Population
timeFrame: 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:
measure: Overall Survival (OS) in the Overall Population
timeFrame: Time to death in months
measure: Overall Survival (OS) in the Female Population
timeFrame: Time to death in months
measure: Objective Response Rate (ORR)
timeFrame: 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
measure: Disease Control Rate (DCR)
timeFrame: RECIST tumour assessments carried out every 6 weeks from randomisation until objective progression
measure: Duration of Response (DoR)
timeFrame: RECIST tumour assessments carried out every 6 weeks from randomisation until objective progression
measure: Time to Deterioration of Disease-related Symptoms (TDS) by Functional Assessment of Cancer Therapy - Lung (FACT-L) Lung Cancer Subscale (LCS).
timeFrame: FACT-L questionnaires are to be administered every 3 weeks after randomisation
measure: Time to Deterioration of Disease-related Symptoms (TDS) by FACT-L Pulmonary Symptom Index (PSI)
timeFrame: FACT-L questionnaires are to be administered every 3 weeks after randomisation
Other outcomes:
Locations:
city: Fullerton
country: United States
facility: Research Site
state: California
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Northridge
country: United States
facility: Research Site
state: California
city: Colorado Springs
country: United States
facility: Research Site
state: Colorado
city: Norwalk
country: United States
facility: Research Site
state: Connecticut
city: Ocala
country: United States
facility: Research Site
state: Florida
city: Marietta
country: United States
facility: Research Site
state: Georgia
city: Joliet
country: United States
facility: Research Site
state: Illinois
city: Park Ridge
country: United States
facility: Research Site
state: Illinois
city: Hutchinson
country: United States
facility: Research Site
state: Kansas
city: Louisville
country: United States
facility: Research Site
state: Kentucky
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Ann Arbor
country: United States
facility: Research Site
state: Michigan
city: St. Louis
country: United States
facility: Research Site
state: Missouri
city: Henderson
country: United States
facility: Research Site
state: Nevada
city: Albany
country: United States
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state: New York
city: Armonk
country: United States
facility: Research Site
state: New York
city: New York
country: United States
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state: New York
city: Durham
country: United States
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state: North Carolina
city: Hickory
country: United States
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state: North Carolina
city: Portland
country: United States
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state: Oregon
city: Austin
country: United States
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state: Texas
city: Houston
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state: Texas
city: Ogden
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state: Utah
city: Alexandria
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state: Virginia
city: Salem
country: United States
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state: Virginia
city: Vancouver
country: United States
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state: Washington
city: Bahía Blanca
country: Argentina
facility: Research Site
city: Capital Federal
country: Argentina
facility: Research Site
city: Ciudad de Buenos Aires
country: Argentina
facility: Research Site
city: Mendoza
country: Argentina
facility: Research Site
city: Rosario
country: Argentina
facility: Research Site
city: Graz
country: Austria
facility: Research Site
city: Grimmenstein
country: Austria
facility: Research Site
city: Innsbruck
country: Austria
facility: Research Site
city: Linz
country: Austria
facility: Research Site
city: Wels
country: Austria
facility: Research Site
city: Wien
country: Austria
facility: Research Site
city: Brussels (Jette)
country: Belgium
facility: Research Site
city: Brussels (Woluwé-St-Lambert)
country: Belgium
facility: Research Site
city: Edegem
country: Belgium
facility: Research Site
city: Genk
country: Belgium
facility: Research Site
city: Liege
country: Belgium
facility: Research Site
city: Fortaleza
country: Brazil
facility: Research Site
city: Goiânia
country: Brazil
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city: Porto Alegre
country: Brazil
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city: Rio de Janeiro
country: Brazil
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city: Sao Paulo
country: Brazil
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city: Edmonton
country: Canada
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state: Alberta
city: Moncton
country: Canada
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state: New Brunswick
city: Halifax
country: Canada
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state: Nova Scotia
city: Kitchener
country: Canada
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state: Ontario
city: London
country: Canada
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state: Ontario
city: Toronto
country: Canada
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state: Ontario
city: Laval
country: Canada
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state: Quebec
city: Quebec
country: Canada
facility: Research Site
city: Beijing
country: China
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city: Chongqing
country: China
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city: Guangzhou
country: China
facility: Research Site
city: Nanjing
country: China
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city: Shanghai
country: China
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city: Wuhan
country: China
facility: Research Site
city: Herlev
country: Denmark
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city: København Ø
country: Denmark
facility: Research Site
city: Odense
country: Denmark
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city: Roskilde
country: Denmark
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city: Vejle
country: Denmark
facility: Research Site
city: Bordeaux Cedex
country: France
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city: Boulogne Billancourt
country: France
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city: Caen Cedex
country: France
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city: Dijon
country: France
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city: Nancy
country: France
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city: Paris
country: France
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city: Pierre Benite Cedex
country: France
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city: Saint Herblain
country: France
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city: Bad Berka
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Essen
country: Germany
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city: Großhansdorf
country: Germany
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city: Halle
country: Germany
facility: Research Site
city: Hamburg
country: Germany
facility: Research Site
city: Heidelberg
country: Germany
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city: Köln
country: Germany
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city: Oldenburg
country: Germany
facility: Research Site
city: Ulm
country: Germany
facility: Research Site
city: Wiesbaden
country: Germany
facility: Research Site
city: Athens
country: Greece
facility: Research Site
city: Heraklion
country: Greece
facility: Research Site
city: Ahmedabad
country: India
facility: Research Site
city: Chennai
country: India
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city: Hyderabad
country: India
facility: Research Site
city: Kolkata
country: India
facility: Research Site
city: New Delhi
country: India
facility: Research Site
city: Pune
country: India
facility: Research Site
city: Vellore
country: India
facility: Research Site
city: Jakarta Timur
country: Indonesia
facility: Research Site
city: Yogyakarta
country: Indonesia
facility: Research Site
city: Ancona
country: Italy
facility: Research Site
city: Avellino
country: Italy
facility: Research Site
city: Bologna
country: Italy
facility: Research Site
city: Genova
country: Italy
facility: Research Site
city: Mantova
country: Italy
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city: Napoli
country: Italy
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city: Orbassano
country: Italy
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city: Parma
country: Italy
facility: Research Site
city: Perugia
country: Italy
facility: Research Site
city: Pisa
country: Italy
facility: Research Site
city: Reggio Emilia
country: Italy
facility: Research Site
city: Akashi-shi
country: Japan
facility: Research Site
city: Fukuoka-shi
country: Japan
facility: Research Site
city: Fukuoka
country: Japan
facility: Research Site
city: Isehara-shi
country: Japan
facility: Research Site
city: Kobe-shi
country: Japan
facility: Research Site
city: Koto-ku
country: Japan
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city: Kumamoto-shi
country: Japan
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city: Matsuyama-shi
country: Japan
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city: Nagoya-shi
country: Japan
facility: Research Site
city: Okayama-shi
country: Japan
facility: Research Site
city: Okazaki-shi
country: Japan
facility: Research Site
city: Osaka-shi
country: Japan
facility: Research Site
city: Osakasayama-shi
country: Japan
facility: Research Site
city: Sakai-shi
country: Japan
facility: Research Site
city: Sapporo-shi
country: Japan
facility: Research Site
city: Shinjuku-ku
country: Japan
facility: Research Site
city: Sunto-gun
country: Japan
facility: Research Site
city: Toyonaka
country: Japan
facility: Research Site
city: Ube-shi
country: Japan
facility: Research Site
city: Utsunomiya-shi
country: Japan
facility: Research Site
city: Yokohama-shi
country: Japan
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Kubang Kerian
country: Malaysia
facility: Research Site
city: Nilai
country: Malaysia
facility: Research Site
city: Penang
country: Malaysia
facility: Research Site
city: Durango
country: Mexico
facility: Research Site
city: Morelia
country: Mexico
facility: Research Site
city: Toluca
country: Mexico
facility: Research Site
city: Amsterdam
country: Netherlands
facility: Research Site
city: Den Bosch
country: Netherlands
facility: Research Site
city: Groningen
country: Netherlands
facility: Research Site
city: Maastricht
country: Netherlands
facility: Research Site
city: Coimbra
country: Portugal
facility: Research Site
city: Funchal
country: Portugal
facility: Research Site
city: Lisboa
country: Portugal
facility: Research Site
city: Porto
country: Portugal
facility: Research Site
city: Vila Nova de Gaia
country: Portugal
facility: Research Site
city: Singapore
country: Singapore
facility: Research Site
city: A Coruña
country: Spain
facility: Research Site
city: Alicante
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Málaga
country: Spain
facility: Research Site
city: Zaragoza
country: Spain
facility: Research Site
city: Chiang Mai
country: Thailand
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Istanbul
country: Turkey
facility: Research Site
city: Izmir
country: Turkey
facility: Research Site
city: Hanoi city
country: Vietnam
facility: Research Site
city: Ho Chi Minh city
country: Vietnam
facility: Research Site
Study officials:
affiliation: Sanofi
name: Contact-US@sanofi.com
role: STUDY_DIRECTOR
References:
citation: 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.
citation: Platt 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.
citation: Heymach 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.
citation: Herbst 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.