ZD6474 (ZACTIMA™) Phase III Study in EGFR Failures

Study Overview
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Brief Summary
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This study is being carried out to assess if adding ZD6474 to best supportive care (BSC) is more effective than best supportive care alone, for the treatment of patients with non-small cell lung cancer, whose disease has recurred after previous chemotherapy and an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR TKI). ZD6474 is a new anti-cancer drug in development that works in a different way to standard chemotherapy drugs. It targets the growth of new blood vessels to a tumour and thereby might slow the rate at which the tumour may grow. Early studies indicate that ZD6474 has a positive effect on the time that a tumour may take to progress to a further stage. Approximately 930 patients will take part in this study. It will be conducted in hospitals and clinics in North and South America, Europe and Asia.

Official Title
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A Phase III Study to Assess the Efficacy of ZD6474 (ZACTIMA™) Plus Best Supportive Care Versus Best Supportive Care in Patients With Locally Advanced or Metastatic (Stage IIIB-IV) Non-Small Cell Lung Cancer After Therapy With an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR TKI)

Conditions
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Non-Small-Cell Lung Carcinoma

Intervention / Treatment
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* Drug: ZD6474 (vandetanib)
* Other: Best Supportive Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with Non-small cell lung cancer for which the standard cancer treatments of surgery, chemotherapy, radiation or other anticancer drugs are no longer appropriate treatments for you. Exclusion Criteria: Patients who have had standard cancer treatments of surgery, chemotherapy or other systemic anti-cancer therapy within 4 weeks before start of study therapy. Three or more prior chemotherapy regimens. Significant cardiovascular events.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: 1<br>Best Supportive Care | Other: Best Supportive Care<br>* standard of care<br>|
| Experimental: 2<br>Vandetanib + Best Supportive Care | Drug: ZD6474 (vandetanib)<br>* once daily oral tablet<br>* Other names: ZACTIMA™;Other: Best Supportive Care<br>* standard of care<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | Overall Survival (OS) is defined as the time from date of randomization until death. Any blinded/unknown patient which 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) | Median time (in months) from randomisation until objective disease progression (determined by RECIST assessments) or death (by any cause in the absence of objective progression) provided death is within 3 months from the last evaluable RECIST assessment | RECIST tumour assessments carried out every 8 weeks from randomisation until objective disease progression | 
| 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 defined by RECIST criteria. The categories for best objective response are CR, PR, stable disease (SD)>= 8 weeks, progressive disease (PD) or NE. | 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 8 weeks from randomisation until objective disease progression. | 
| Disease Control Rate (DCR) | Disease control rate is defined as the number of patients who achieved disease control at 8 weeks following randomisation. Disease control at 8 weeks is defined as a best objective response of complete response (CR), partial response (PR) or stable disease (SD) >= 8 weeks | RECIST tumour assessments carried out every 8 weeks from randomisation until objective disease progression | 
| 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 8 weeks from randomisation until objective disease progression | 
| Time to Deterioration of Disease-related Symptoms (TDS) by Questionnaire - the Lung Cancer Subscale (LCS) a Selection of the FACT-L Focusing on Symptoms of Lung Cancer Plus Pain and Fatigue (LCS-PF) | Time to deterioration in symptoms is defined as the interval from the date of randomization to the first assessment of 'worsened' with no visit assessment of 'improved' within the next 28 days. Where assessment is by a selection of questions from the Functional Assessment of Cancer Therapy for Lung Cancer (FACT-L) questionnaire. | Disease-related symptom assessments are to be administered at screening (within 7 days before the first dose of study medication) and every 4 weeks thereafter, at discontinuation of study treatment and at the 30-day follow-up visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-Small-Cell Lung Carcinoma, Adenocarcinoma, Squamous Cell Carcinoma, Large Cell Carcinoma