ZACTIMA (an Anti-EGFR / Anti-VEGF Agent) Combined With Docetaxel Compared to Docetaxel in Non-small Cell Lung Cancer

Lung Cancer Clinical Trial

— ZODIAC  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00312377
• Other study ID #: D4200C00032
• Secondary ID: 6474IL/0032
• Status: Completed
• Phase: Phase 3
• First received: April 6, 2006
• Last updated: August 29, 2014
• Start date: May 2006
• Est. completion date: March 2014

Study information

• Verified date: August 2014
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1690
• Est. completion date: March 2014
• Est. primary completion date: August 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Cancer
• Lung Neoplasms
• Non-small Cell Lung Cancer

Intervention

Drug:
• Docetaxel
infusion
• Vandetanib
oral

Locations

Country	Name	City	State
Argentina	Research Site	Bahía Blanca
Argentina	Research Site	Capital Federal
Argentina	Research Site	Ciudad de Buenos Aires
Argentina	Research Site	Mendoza
Argentina	Research Site	Rosario
Austria	Research Site	Graz
Austria	Research Site	Grimmenstein
Austria	Research Site	Innsbruck
Austria	Research Site	Linz
Austria	Research Site	Wels
Austria	Research Site	Wien
Belgium	Research Site	Brussels (Jette)
Belgium	Research Site	Brussels (Woluwé-St-Lambert)
Belgium	Research Site	Edegem
Belgium	Research Site	Genk
Belgium	Research Site	Liege
Brazil	Research Site	Fortaleza
Brazil	Research Site	Goiânia
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Rio de Janeiro
Brazil	Research Site	Sao Paulo
Canada	Research Site	Edmonton	Alberta
Canada	Research Site	Halifax	Nova Scotia
Canada	Research Site	Kitchener	Ontario
Canada	Research Site	Laval	Quebec
Canada	Research Site	London	Ontario
Canada	Research Site	Moncton	New Brunswick
Canada	Research Site	Quebec
Canada	Research Site	Toronto	Ontario
China	Research Site	Beijing
China	Research Site	Chongqing
China	Research Site	Guangzhou
China	Research Site	Nanjing
China	Research Site	Shanghai
China	Research Site	Wuhan
Denmark	Research Site	Herlev
Denmark	Research Site	København Ø
Denmark	Research Site	Odense
Denmark	Research Site	Roskilde
Denmark	Research Site	Vejle
France	Research Site	Bordeaux Cedex
France	Research Site	Boulogne Billancourt
France	Research Site	Caen Cedex
France	Research Site	Dijon
France	Research Site	Nancy
France	Research Site	Paris
France	Research Site	Pierre Benite Cedex
France	Research Site	Saint Herblain
Germany	Research Site	Bad Berka
Germany	Research Site	Berlin
Germany	Research Site	Essen
Germany	Research Site	Großhansdorf
Germany	Research Site	Halle
Germany	Research Site	Hamburg
Germany	Research Site	Heidelberg
Germany	Research Site	Köln
Germany	Research Site	Oldenburg
Germany	Research Site	Ulm
Germany	Research Site	Wiesbaden
Greece	Research Site	Athens
Greece	Research Site	Heraklion
India	Research Site	Ahmedabad
India	Research Site	Chennai
India	Research Site	Hyderabad
India	Research Site	Kolkata
India	Research Site	New Delhi
India	Research Site	Pune
India	Research Site	Vellore
Indonesia	Research Site	Jakarta Timur
Indonesia	Research Site	Yogyakarta
Italy	Research Site	Ancona
Italy	Research Site	Avellino
Italy	Research Site	Bologna
Italy	Research Site	Genova
Italy	Research Site	Mantova
Italy	Research Site	Napoli
Italy	Research Site	Orbassano
Italy	Research Site	Parma
Italy	Research Site	Perugia
Italy	Research Site	Pisa
Italy	Research Site	Reggio Emilia
Japan	Research Site	Akashi-shi
Japan	Research Site	Fukuoka
Japan	Research Site	Fukuoka-shi
Japan	Research Site	Isehara-shi
Japan	Research Site	Kobe-shi
Japan	Research Site	Koto-ku
Japan	Research Site	Kumamoto-shi
Japan	Research Site	Matsuyama-shi
Japan	Research Site	Nagoya-shi
Japan	Research Site	Okayama-shi
Japan	Research Site	Okazaki-shi
Japan	Research Site	Osaka-shi
Japan	Research Site	Osakasayama-shi
Japan	Research Site	Sakai-shi
Japan	Research Site	Sapporo-shi
Japan	Research Site	Shinjuku-ku
Japan	Research Site	Sunto-gun
Japan	Research Site	Toyonaka
Japan	Research Site	Ube-shi
Japan	Research Site	Utsunomiya-shi
Japan	Research Site	Yokohama-shi
Korea, Republic of	Research Site	Seoul
Malaysia	Research Site	Kubang Kerian
Malaysia	Research Site	Nilai
Malaysia	Research Site	Penang
Mexico	Research Site	Durango
Mexico	Research Site	Morelia
Mexico	Research Site	Toluca
Netherlands	Research Site	Amsterdam
Netherlands	Research Site	Den Bosch
Netherlands	Research Site	Groningen
Netherlands	Research Site	Maastricht
Portugal	Research Site	Coimbra
Portugal	Research Site	Funchal
Portugal	Research Site	Lisboa
Portugal	Research Site	Porto
Portugal	Research Site	Vila Nova de Gaia
Singapore	Research Site	Singapore
Spain	Research Site	A Coruña
Spain	Research Site	Alicante
Spain	Research Site	Madrid
Spain	Research Site	Málaga
Spain	Research Site	Zaragoza
Thailand	Research Site	Chiang Mai
Turkey	Research Site	Ankara
Turkey	Research Site	Istanbul
Turkey	Research Site	Izmir
United States	Research Site	Albany	New York
United States	Research Site	Alexandria	Virginia
United States	Research Site	Ann Arbor	Michigan
United States	Research Site	Armonk	New York
United States	Research Site	Austin	Texas
United States	Research Site	Boston	Massachusetts
United States	Research Site	Colorado Springs	Colorado
United States	Research Site	Durham	North Carolina
United States	Research Site	Fullerton	California
United States	Research Site	Henderson	Nevada
United States	Research Site	Hickory	North Carolina
United States	Research Site	Houston	Texas
United States	Research Site	Hutchinson	Kansas
United States	Research Site	Joliet	Illinois
United States	Research Site	Los Angeles	California
United States	Research Site	Louisville	Kentucky
United States	Research Site	Marietta	Georgia
United States	Research Site	New York	New York
United States	Research Site	Northridge	California
United States	Research Site	Norwalk	Connecticut
United States	Research Site	Ocala	Florida
United States	Research Site	Ogden	Utah
United States	Research Site	Park Ridge	Illinois
United States	Research Site	Portland	Oregon
United States	Research Site	Salem	Virginia
United States	Research Site	St. Louis	Missouri
United States	Research Site	Vancouver	Washington
Vietnam	Research Site	Hanoi city
Vietnam	Research Site	Ho Chi Minh city

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Vietnam,  Argentina,  Austria,  Belgium,  Brazil,  Canada,  China,  Denmark,  France,  Germany,  Greece,  India,  Indonesia,  Italy,  Japan,  Korea, Republic of,  Malaysia,  Mexico,  Netherlands,  Portugal,  Singapore,  Spain,  Thailand,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Secondary	Overall Survival (OS) in the Overall Population	Overall survival is defined as the time from date of randomization until death. Any patient not known to have died at the time of analysis will be censored based on the last recorded date on which the patient was known to be alive (ie their status must be known at the censored date and should not be lost to follow up or unknown).	Time to death in months	No
Secondary	Overall Survival (OS) in the Female Population	Overall survival is defined as the time from date of randomization until death. Any patient not known to have died at the time of analysis will be censored based on the last recorded date on which the patient was known to be alive (ie their status must be known at the censored date and should not be lost to follow up or unknown).	Time to death in months	No
Secondary	Objective Response Rate (ORR)	The ORR is the number of patients that are responders ie those patients with a confirmed best objective response of complete response (CR) or partial response (PR) as determined according to RECIST 1.0. CR is defined as the disappearance of all target lesions with no evidence of tumour elsewhere and PR is defined as at least a 30% reduction in the total tumour size of measurable lesions with no new lesions and no progression in the non-target lesions.	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	No
Secondary	Disease Control Rate (DCR)	Disease control rate is defined as the number of patients who achieved disease control at least 6 weeks following randomisation. Disease control at 6 weeks is defined as a best objective response of complete response (CR), partial response (PR) or stable disease (SD) >= 6 weeks as determined according to RECIST 1.0. CR is defined as the disappearance of all target lesions with no evidence of tumour elsewhere, PR is defined as at least a 30% reduction in the total tumour size of measurable lesions with no new lesions and no progression in the non-target lesions and SD >= 6 is assigned to patients who have not responded and have no evidence of progression at least 6 weeks after randomisation.	RECIST tumour assessments carried out every 6 weeks from randomisation until objective progression	No
Secondary	Duration of Response (DoR)	Response is defined as a confirmed best objective response of CR or PR. Duration of response is defined as time from the date of first documented response until date of documented progression or death in the absence of disease progression (provided death is within 3 months of last RECIST assessment)	RECIST tumour assessments carried out every 6 weeks from randomisation until objective progression	No
Secondary	Time to Deterioration of Disease-related Symptoms (TDS) by Functional Assessment of Cancer Therapy - Lung (FACT-L) Lung Cancer Subscale (LCS).	The lung cancer subscale (LCS) consists of 7 items of the FACT-L (3 items relating to breathing/dyspnea, and 1 item each relating to cough, weight loss, appetite, and cognition). The LCS total score is the sum of the scores from the 7 items.; Time to deterioration is defined as the interval from the date of randomization to the first assessment of worsened without an improvement in the next 21 days.; A patient will be defined as having a deterioration in symptoms if they have a single visit assessment of 'worsened' with no visit assessment of 'improved' within the next 21 days.	FACT-L questionnaires are to be administered every 3 weeks after randomisation	No
Secondary	Time to Deterioration of Disease-related Symptoms (TDS) by FACT-L Pulmonary Symptom Index (PSI)	The pulmonary symptom index (PSI) consists of 4 items of the LCS relating to pulmonary symptoms (i.e. 3 items relating to breathing/dyspnea, and 1 item relating to cough). The PSI score is the sum of the scores from the 4 items.; Time to deterioration is defined as the interval from the date of randomization to the first assessment of worsened without an improvement in the next 21 days.; A patient will be defined as having a deterioration in symptoms if they have a single visit assessment of 'worsened' with no visit assessment of 'improved' within the next 21 days.	FACT-L questionnaires are to be administered every 3 weeks after randomisation	No

External Links

•   AstraZeneca Clinical Trial Information - Outside US
•   Cancer Study Locator (US and Canada Only)
•   CSP Redacted
•   CSR-D4200C00032.pdf