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 11, 2014
Last verified: August 2014
Results First Received: April 27, 2011  
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
Conditions: Non-small Cell Lung Cancer
Lung Cancer
Interventions: Drug: Docetaxel
Drug: Vandetanib

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
First patient enrolled 08 May 2006, last patient enrolled 14 March 2008, cut off date 22 August 2008

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Vandetanib 100 mg Plus Docetaxel Vandetanib 100 mg oral tablet taken once daily in combination with docetaxel 75 mg/m2 IVb infusion every 21 days up to a maximum of 6 cycles
Placebo Plus Docetaxel Placebo tablet taken once daily plus docetaxel 75 mg/m2 IVb infusion every 21 days up to a maximum of 6 cycles

Participant Flow:   Overall Study
    Vandetanib 100 mg Plus Docetaxel     Placebo Plus Docetaxel  
STARTED     694 [1]   697 [1]
COMPLETED     50 [2]   29 [2]
NOT COMPLETED     644     668  
Death                 403                 418  
Withdrawal by Subject                 23                 30  
Lost to Follow-up                 9                 12  
Non-compliance                 0                 2  
Randomised but never received treatment                 6                 6  
Discontinue treatment survival follow up                 202                 200  
Site ended participation in study                 1                 0  
[1] randomised patients
[2] ongoing study treatment at data cut-off



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Vandetanib 100 mg Plus Docetaxel Vandetanib 100 mg plus docetaxel
Placebo Plus Docetaxel Placebo plus docetaxel
Total Total of all reporting groups

Baseline Measures
    Vandetanib 100 mg Plus Docetaxel     Placebo Plus Docetaxel     Total  
Number of Participants  
[units: participants]
  694     697     1391  
Age  
[units: years]
Mean ( Full Range )
  58.5  
  ( 28 to 82 )  
  58.4  
  ( 20 to 82 )  
  58.45  
  ( 20 to 82 )  
Gender  
[units: Participants]
     
Female     497     473     970  
Male     197     224     421  



  Outcome Measures
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1.  Primary:   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 ]

Measure Type Primary
Measure Title Progression-Free Survival (PFS) in the Overall Population
Measure Description 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.
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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Vandetanib 100 mg Plus Docetaxel Vandetanib 100 mg plus docetaxel
Placebo Plus Docetaxel Placebo plus docetaxel

Measured Values
    Vandetanib 100 mg Plus Docetaxel     Placebo Plus Docetaxel  
Number of Participants Analyzed  
[units: participants]
  694     697  
Progression-Free Survival (PFS) in the Overall Population  
[units: Weeks]
Median ( 95% Confidence Interval )
  17.3  
  ( 15 to 18 )  
  14  
  ( 12.7 to 16.9 )  

No statistical analysis provided for Progression-Free Survival (PFS) in the Overall Population



2.  Primary:   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 ]

Measure Type Primary
Measure Title Progression-Free Survival (PFS) in the Female Population
Measure Description 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.
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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Vandetanib 100 mg Plus Docetaxel Vandetanib 100 mg plus docetaxel
Placebo Plus Docetaxel Placebo plus docetaxel

Measured Values
    Vandetanib 100 mg Plus Docetaxel     Placebo Plus Docetaxel  
Number of Participants Analyzed  
[units: participants]
  197     224  
Progression-Free Survival (PFS) in the Female Population  
[units: Weeks]
Median ( 95% Confidence Interval )
  20.1  
  ( 17.9 to 23.9 )  
  18.3  
  ( 15 to 22.1 )  

No statistical analysis provided for Progression-Free Survival (PFS) in the Female Population



3.  Secondary:   Overall Survival (OS) in the Overall Population   [ Time Frame: Time to death in months ]

Measure Type Secondary
Measure Title Overall Survival (OS) in the Overall Population
Measure Description 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 Frame Time to death in months  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Vandetanib 100 mg Plus Docetaxel Vandetanib 100 mg plus docetaxel
Placebo Plus Docetaxel Placebo plus docetaxel

Measured Values
    Vandetanib 100 mg Plus Docetaxel     Placebo Plus Docetaxel  
Number of Participants Analyzed  
[units: participants]
  694     697  
Overall Survival (OS) in the Overall Population  
[units: Months]
Median ( 95% Confidence Interval )
  10.6  
  ( 9.6 to 11.5 )  
  10  
  ( 9.2 to 10.8 )  

No statistical analysis provided for Overall Survival (OS) in the Overall Population



4.  Secondary:   Overall Survival (OS) in the Female Population   [ Time Frame: Time to death in months ]

Measure Type Secondary
Measure Title Overall Survival (OS) in the Female Population
Measure Description 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 Frame Time to death in months  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Vandetanib 100 mg Plus Docetaxel Vandetanib 100 mg plus docetaxel
Placebo Plus Docetaxel Placebo plus docetaxel

Measured Values
    Vandetanib 100 mg Plus Docetaxel     Placebo Plus Docetaxel  
Number of Participants Analyzed  
[units: participants]
  197     224  
Overall Survival (OS) in the Female Population  
[units: Months]
Median ( 95% Confidence Interval )
  12.7  
  ( 10.5 to 17.1 )  
  14.2  
  ( 10.8 to 16.2 )  

No statistical analysis provided for Overall Survival (OS) in the Female Population



5.  Secondary:   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 ]

Measure Type Secondary
Measure Title Objective Response Rate (ORR)
Measure Description 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.
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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Vandetanib 100 mg Plus Docetaxel Vandetanib 100 mg plus docetaxel
Placebo Plus Docetaxel Placebo plus docetaxel

Measured Values
    Vandetanib 100 mg Plus Docetaxel     Placebo Plus Docetaxel  
Number of Participants Analyzed  
[units: participants]
  694     697  
Objective Response Rate (ORR)  
[units: Participants]
  120     71  

No statistical analysis provided for Objective Response Rate (ORR)



6.  Secondary:   Disease Control Rate (DCR)   [ Time Frame: RECIST tumour assessments carried out every 6 weeks from randomisation until objective progression ]

Measure Type Secondary
Measure Title Disease Control Rate (DCR)
Measure Description 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.
Time Frame RECIST tumour assessments carried out every 6 weeks from randomisation until objective progression  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Vandetanib 100 mg Plus Docetaxel Vandetanib 100 mg plus docetaxel
Placebo Plus Docetaxel Placebo plus docetaxel

Measured Values
    Vandetanib 100 mg Plus Docetaxel     Placebo Plus Docetaxel  
Number of Participants Analyzed  
[units: participants]
  694     697  
Disease Control Rate (DCR)  
[units: Participants]
  413     380  

No statistical analysis provided for Disease Control Rate (DCR)



7.  Secondary:   Duration of Response (DoR)   [ Time Frame: RECIST tumour assessments carried out every 6 weeks from randomisation until objective progression ]

Measure Type Secondary
Measure Title Duration of Response (DoR)
Measure Description 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 Frame RECIST tumour assessments carried out every 6 weeks from randomisation until objective progression  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Vandetanib 100 mg Plus Docetaxel Vandetanib 100 mg plus docetaxel
Placebo Plus Docetaxel Placebo plus docetaxel

Measured Values
    Vandetanib 100 mg Plus Docetaxel     Placebo Plus Docetaxel  
Number of Participants Analyzed  
[units: participants]
  694     697  
Duration of Response (DoR)  
[units: Weeks]
Median ( Full Range )
  29.9  
  ( 7.14 to 72.29 )  
  19.7  
  ( 9.71 to 41.86 )  

No statistical analysis provided for Duration of Response (DoR)



8.  Secondary:   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 ]

Measure Type Secondary
Measure Title Time to Deterioration of Disease-related Symptoms (TDS) by Functional Assessment of Cancer Therapy - Lung (FACT-L) Lung Cancer Subscale (LCS).
Measure Description

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 Frame FACT-L questionnaires are to be administered every 3 weeks after randomisation  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Vandetanib 100 mg Plus Docetaxel Vandetanib 100 mg plus docetaxel
Placebo Plus Docetaxel Placebo plus docetaxel

Measured Values
    Vandetanib 100 mg Plus Docetaxel     Placebo Plus Docetaxel  
Number of Participants Analyzed  
[units: participants]
  694     697  
Time to Deterioration of Disease-related Symptoms (TDS) by Functional Assessment of Cancer Therapy - Lung (FACT-L) Lung Cancer Subscale (LCS).  
[units: Weeks]
Median ( Inter-Quartile Range )
  15  
  ( 6.1 to 82.3 )  
  11.9  
  ( 6.0 to 28.1 )  

No statistical analysis provided for Time to Deterioration of Disease-related Symptoms (TDS) by Functional Assessment of Cancer Therapy - Lung (FACT-L) Lung Cancer Subscale (LCS).



9.  Secondary:   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 ]

Measure Type Secondary
Measure Title Time to Deterioration of Disease-related Symptoms (TDS) by FACT-L Pulmonary Symptom Index (PSI)
Measure Description

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.

Time Frame FACT-L questionnaires are to be administered every 3 weeks after randomisation  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Vandetanib 100 mg Plus Docetaxel Vandetanib 100 mg plus docetaxel
Placebo Plus Docetaxel Placebo plus docetaxel

Measured Values
    Vandetanib 100 mg Plus Docetaxel     Placebo Plus Docetaxel  
Number of Participants Analyzed  
[units: participants]
  694     697  
Time to Deterioration of Disease-related Symptoms (TDS) by FACT-L Pulmonary Symptom Index (PSI)  
[units: Weeks]
Median ( Inter-Quartile Range )
  12.3  
  ( 5.9 to 36.7 )  
  11.9  
  ( 6 to 28.4 )  

No statistical analysis provided for Time to Deterioration of Disease-related Symptoms (TDS) by FACT-L Pulmonary Symptom Index (PSI)




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


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