Efficacy Trial Comparing ZD6474 With Erlotinib in NSCLC After Failure of at Least One Prior Chemotherapy

Study Overview
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Brief Summary
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To determine if ZD6474 a new investigational drug, is effective in treating Non Small Lung Cancer and if so, how it compares with another type of anti cancer therapy chemotherapy, Erlotinib

Official Title
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A Phase III, International, Randomised, Double Blind, Parallel-Group Study to Assess the Efficacy of Zactima™ Versus Tarceva® in Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer After Failure of at Least One Prior Chemotherapy

Conditions
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Non Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Vandetanib
* Drug: Erlotinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed locally advanced or metastatic NSCLC Failure of at least one but not more than two prior chemotherapy regimens Exclusion Criteria: Prior treatment with erlotinib (Tarceva), gefitinib (IRESSA), sunitinib (Sutent), sorafenib (Nexavar) Chemotherapy or other type of anti cancer therapy within 4 weeks of study start

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 |
| --- | --- |
| Active Comparator: 1<br>Erlotinib | Drug: Erlotinib<br>* oral dose<br>* Other names: Tarceva®;|
| Experimental: 2<br>Vandetanib | Drug: Vandetanib<br>* once daily oral tablet<br>* Other names: ZACTIMA™;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) | 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 Response Evaluation Criteria In Solid Tumors (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. | progressionRECIST tumour assessments carried out every 4 weeks up to week 16 then every 8 weeks thereafter from randomisation until the date of first documented objective disease progression or date of death from any cause, whichever came first, assessed. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | 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) | 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. | RECIST tumour assessments every 4 weeks up to week 16 then every 8 weeks thereafter from randomisation until the date of first documented objective disease progression or date of death from any cause, whichever came first, assessed up to 21 months | 
| Disease Control Rate (DCR) | Disease control rate is defined as the number of patients who achieved disease control at least 8 weeks following randomisation. Disease control is defined as a best objective response of complete response (CR), partial response (PR) or stable disease (SD) >= 8 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 >= 8 is assigned to patients who have not responded and have no evidence of progression at least 8 weeks after randomisation. | RECIST tumour assessments carried out every 4 weeks until week 16 then every 8 weeks thereafter (+/- 3 days) from randomisation until objective progression | 
| Time to Deterioration of Disease-related Symptoms (TDS) by EORTC Quality of Life Questionnaire - Pain | Pain was assessed as the average score of two items: Question 9 (Have you had pain) and 19 (Did pain interfere with your daily activities) of the QLQ-C30. Time to deterioration in symptoms is defined as the interval from the date of randomization to the first assessment of worsened without an improvement in the next 28 days. A patient is 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 28 days. | Disease-related symptom assessments are to be administered at screening (within 7 days before the first dose of study medication), every 4 weeks thereafter, at discontinuation of study treatment and at the 30-day follow-up visit | 
| Time to Deterioration of Disease-related Symptoms (TDS) by EORTC Quality of Life Questionnaire - Dyspnoea | Dyspnea was assessed as the average score of four items: Question 8 of the QLQ-C30 (Were you short of breath) and Question 3 of the QLQ-C30 (Were you short of breath when you rested), Questions 4 (Were you short of breath when you walked) and 5 (Were you short of breath when you climbed stairs) of the QLQ-LC13 (or, equivalently, Questions 33, 34 and 35 of the combined QLQ-C30 and QLQ-LC13 questionnaires). Time to deterioration in symptoms is defined as the interval from the date of randomization to the first assessment of worsened without an improvement in the next 28 days. A patient is 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 28 days. | Disease-related symptom assessments are to be administered at screening (within 7 days before the first dose of study medication), every 4 weeks thereafter, at discontinuation of study treatment and at the 30-day follow-up visit | 
| Time to Deterioration of Disease-related Symptoms (TDS) by EORTC Quality of Life Questionnaire - Cough | Cough was assessed using Question 1 (How much did you cough) of the QLQ-LC13 (or, equivalently, Question 31 of the combined QLQ-C30 and QLQ-LC13 questionnaires). Time to deterioration in symptoms is defined as the interval from the date of randomization to the first assessment of worsened without an improvement in the next 28 days. A patient is 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 28 days. | Disease-related symptom assessments are to be administered at screening (within 7 days before the first dose of study medication), 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 Cancer, NSCLC