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

August 24, 2016 updated by: Genzyme, a Sanofi Company

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

1690

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
      • Bahía Blanca, Argentina
        • Research Site
      • Capital Federal, Argentina
        • Research Site
      • Ciudad de Buenos Aires, Argentina
        • Research Site
      • Mendoza, Argentina
        • Research Site
      • Rosario, Argentina
        • Research Site
  • Austria
      • Graz, Austria
        • Research Site
      • Grimmenstein, Austria
        • Research Site
      • Innsbruck, Austria
        • Research Site
      • Linz, Austria
        • Research Site
      • Wels, Austria
        • Research Site
      • Wien, Austria
        • Research Site
  • Belgium
      • Brussels (Jette), Belgium
        • Research Site
      • Brussels (Woluwé-St-Lambert), Belgium
        • Research Site
      • Edegem, Belgium
        • Research Site
      • Genk, Belgium
        • Research Site
      • Liege, Belgium
        • Research Site
  • Brazil
      • Fortaleza, Brazil
        • Research Site
      • Goiânia, Brazil
        • Research Site
      • Porto Alegre, Brazil
        • Research Site
      • Rio de Janeiro, Brazil
        • Research Site
      • Sao Paulo, Brazil
        • Research Site
  • Canada
      • Quebec, Canada
        • Research Site
    • Alberta
      • Edmonton, Alberta, Canada
        • Research Site
    • New Brunswick
      • Moncton, New Brunswick, Canada
        • Research Site
    • Nova Scotia
      • Halifax, Nova Scotia, Canada
        • Research Site
    • Ontario
      • Kitchener, Ontario, Canada
        • Research Site
      • London, Ontario, Canada
        • Research Site
      • Toronto, Ontario, Canada
        • Research Site
    • Quebec
      • Laval, Quebec, Canada
        • Research Site
  • China
      • Beijing, China
        • Research Site
      • Chongqing, China
        • Research Site
      • Guangzhou, China
        • Research Site
      • Nanjing, China
        • Research Site
      • Shanghai, China
        • Research Site
      • Wuhan, China
        • Research Site
  • Denmark
      • Herlev, Denmark
        • Research Site
      • København Ø, Denmark
        • Research Site
      • Odense, Denmark
        • Research Site
      • Roskilde, Denmark
        • Research Site
      • Vejle, Denmark
        • Research Site
  • France
      • 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, France
        • Research Site
  • Germany
      • 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, Germany
        • Research Site
  • Greece
      • Athens, Greece
        • Research Site
      • Heraklion, Greece
        • Research Site
  • India
      • 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, India
        • Research Site
  • Indonesia
      • Jakarta Timur, Indonesia
        • Research Site
      • Yogyakarta, Indonesia
        • Research Site
  • Italy
      • 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, Italy
        • Research Site
  • Japan
      • 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, Japan
        • Research Site
  • Korea, Republic of
      • Seoul, Korea, Republic of
        • Research Site
  • Malaysia
      • Kubang Kerian, Malaysia
        • Research Site
      • Nilai, Malaysia
        • Research Site
      • Penang, Malaysia
        • Research Site
  • Mexico
      • Durango, Mexico
        • Research Site
      • Morelia, Mexico
        • Research Site
      • Toluca, Mexico
        • Research Site
  • Netherlands
      • Amsterdam, Netherlands
        • Research Site
      • Den Bosch, Netherlands
        • Research Site
      • Groningen, Netherlands
        • Research Site
      • Maastricht, Netherlands
        • Research Site
  • Portugal
      • Coimbra, Portugal
        • Research Site
      • Funchal, Portugal
        • Research Site
      • Lisboa, Portugal
        • Research Site
      • Porto, Portugal
        • Research Site
      • Vila Nova de Gaia, Portugal
        • Research Site
  • Singapore
      • Singapore, Singapore
        • Research Site
  • Spain
      • A Coruña, Spain
        • Research Site
      • Alicante, Spain
        • Research Site
      • Madrid, Spain
        • Research Site
      • Málaga, Spain
        • Research Site
      • Zaragoza, Spain
        • Research Site
  • Thailand
      • Chiang Mai, Thailand
        • Research Site
  • Turkey
      • Ankara, Turkey
        • Research Site
      • Istanbul, Turkey
        • Research Site
      • Izmir, Turkey
        • Research Site
  • United States
    • California
      • Fullerton, California, United States
        • Research Site
      • Los Angeles, California, United States
        • Research Site
      • Northridge, California, United States
        • Research Site
    • Colorado
      • Colorado Springs, Colorado, United States
        • Research Site
    • Connecticut
      • Norwalk, Connecticut, United States
        • Research Site
    • Florida
      • Ocala, Florida, United States
        • Research Site
    • Georgia
      • Marietta, Georgia, United States
        • Research Site
    • Illinois
      • Joliet, Illinois, United States
        • Research Site
      • Park Ridge, Illinois, United States
        • Research Site
    • Kansas
      • Hutchinson, Kansas, United States
        • Research Site
    • Kentucky
      • Louisville, Kentucky, United States
        • Research Site
    • Massachusetts
      • Boston, Massachusetts, United States
        • Research Site
    • Michigan
      • Ann Arbor, Michigan, United States
        • Research Site
    • Missouri
      • St. Louis, Missouri, United States
        • Research Site
    • Nevada
      • Henderson, Nevada, United States
        • Research Site
    • New York
      • Albany, New York, United States
        • Research Site
      • Armonk, New York, United States
        • Research Site
      • New York, New York, United States
        • Research Site
    • North Carolina
      • Durham, North Carolina, United States
        • Research Site
      • Hickory, North Carolina, United States
        • Research Site
    • Oregon
      • Portland, Oregon, United States
        • Research Site
    • Texas
      • Austin, Texas, United States
        • Research Site
      • Houston, Texas, United States
        • Research Site
    • Utah
      • Ogden, Utah, United States
        • Research Site
    • Virginia
      • Alexandria, Virginia, United States
        • Research Site
      • Salem, Virginia, United States
        • Research Site
    • Washington
      • Vancouver, Washington, United States
        • Research Site
  • Vietnam
      • Hanoi city, Vietnam
        • Research Site
      • Ho Chi Minh city, Vietnam
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 2
Vandetanib + Docetaxel
Drug: Docetaxel
infusion
Other Names:
  • TAXOTERE™
Drug: Vandetanib
oral
Other Names:
  • ZD6474
  • ZACTIMA™
Active Comparator: 1
Docetaxel monotherapy
Drug: Docetaxel
infusion
Other Names:
  • TAXOTERE™

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-Free Survival (PFS) in the Overall Population
Time Frame: 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
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
Time Frame: 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
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival (OS) in the Overall Population
Time Frame: Time to death in months
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
Overall Survival (OS) in the Female Population
Time Frame: Time to death in months
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
Objective Response Rate (ORR)
Time Frame: 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
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
Disease Control Rate (DCR)
Time Frame: RECIST tumour assessments carried out every 6 weeks from randomisation until objective progression
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
Duration of Response (DoR)
Time Frame: RECIST tumour assessments carried out every 6 weeks from randomisation until objective progression
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
Time to Deterioration of Disease-related Symptoms (TDS) by Functional Assessment of Cancer Therapy - Lung (FACT-L) Lung Cancer Subscale (LCS).
Time Frame: FACT-L questionnaires are to be administered every 3 weeks after randomisation

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
Time to Deterioration of Disease-related Symptoms (TDS) by FACT-L Pulmonary Symptom Index (PSI)
Time Frame: FACT-L questionnaires are to be administered every 3 weeks after randomisation

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Genzyme, a Sanofi Company

Investigators

  • Study Director: Contact-US@sanofi.com, Sanofi

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2006

Primary Completion (Actual)

August 1, 2008

Study Completion (Actual)

March 1, 2014

Study Registration Dates

First Submitted

April 6, 2006

First Submitted That Met QC Criteria

April 6, 2006

First Posted (Estimate)

April 10, 2006

Study Record Updates

Last Update Posted (Estimate)

September 30, 2016

Last Update Submitted That Met QC Criteria

August 24, 2016

Last Verified

August 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • D4200C00032
  • 6474IL/0032
  • 2005-004749-32 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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