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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT00312377
First received: April 6, 2006
Last updated: August 29, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Non-small Cell Lung Cancer
Lung Cancer
Drug: Docetaxel
Drug: Vandetanib
Phase 3

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

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Overall Survival (OS) in the Overall Population [ Time Frame: Time to death in months ] [ Designated as safety issue: No ]
    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).

  • Overall Survival (OS) in the Female Population [ Time Frame: Time to death in months ] [ Designated as safety issue: No ]
    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).

  • 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 ] [ Designated as safety issue: No ]
    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.

  • Disease Control Rate (DCR) [ Time Frame: RECIST tumour assessments carried out every 6 weeks from randomisation until objective progression ] [ Designated as safety issue: No ]
    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.

  • Duration of Response (DoR) [ Time Frame: RECIST tumour assessments carried out every 6 weeks from randomisation until objective progression ] [ Designated as safety issue: No ]
    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)

  • 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 ] [ Designated as safety issue: No ]

    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.


  • 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 ] [ Designated as safety issue: No ]

    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.



Enrollment: 1690
Study Start Date: May 2006
Study Completion Date: March 2014
Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Docetaxel monotherapy
Drug: Docetaxel
infusion
Other Name: TAXOTERE™
Experimental: 2
Vandetanib + Docetaxel
Drug: Docetaxel
infusion
Other Name: TAXOTERE™
Drug: Vandetanib
oral
Other Names:
  • ZACTIMA™
  • ZD6474

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00312377

  Show 157 Study Locations
Sponsors and Collaborators
AstraZeneca
Investigators
Study Director: AstraZeneca Zactima Medical Science Director, MD AstraZeneca
  More Information

Additional Information:
No publications provided by AstraZeneca

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT00312377     History of Changes
Other Study ID Numbers: D4200C00032, 6474IL/0032
Study First Received: April 6, 2006
Results First Received: April 27, 2011
Last Updated: August 29, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by AstraZeneca:
Non-small cell lung cancer
NSCLC

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Docetaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 01, 2014