Phase II of Zactima Maintenance for Locally Advanced or Metastatic Non-small-cell Lung Carcinoma (NSCLC) Following Platinum-doublet Chemotherapy

Study Overview
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Brief Summary
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This study is multicenter, randomized, double-blinded, placebo-controlled Phase II study comparing vandetanib (300mg daily) plus best supportive care (BSC) to placebo plus BSC as maintenance treatment in patients with locally advanced or metastatic NSCLC, who have received and responded to prior platinum-doublet systemic chemotherapy. The primary objective of the study is to compare the Progression Free Survival (PFS) rate at 3 months in locally advanced or metastatic NSCLC patients with or without vandetanib maintenance.

Official Title
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Randomized, Double-blinded, Placebo-controlled Phase II Study of Vandetanib (ZactimaTM) Maintenance for Locally Advanced or Metastatic Non-small-cell Lung Carcinoma (NSCLC) Following Platinum-doublet Chemotherapy

Conditions
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NSCLC

Intervention / Treatment
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* Drug: Vandetanib
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologic or cytologic confirmation of locally advanced or metastatic NSCLC (IIIb-IV) at the time of original diagnosis. Completion of 4 cycles of chemotherapy of gemcitabine (1,000 or 1250mg/m^2/day on day 1 and 8) and cisplatin (70-80mg/m^2/day on day 1) every 3 weeks and have shown response, Complete Response(CR), Partial Response (PR) or stable disease (SD) by RECIST. WHO PS 0-1 No prior radiotherapy to chest, immunotherapy or biologic therapy Exclusion Criteria: Mixed small cell and non small-cell lung cancer history. Prior treatment with EGFR TKIs or VEGFR TKIs (prior treatment with cetuximab [Erbitux] or bevacizumab [Avastin] is not permitted.) Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the investigator's opinion makes it undesirable for the patient to participate in the study or which would jeopardize compliance with the protocol. Radiation therapy within 4 weeks before the start of study therapy. Major surgery within 4 weeks, or incomplete healed surgical incision before starting study therapy.

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vandetanib<br> | Drug: Vandetanib<br>* Tablet, oral, daily<br>* Other names: Zactima TM;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) Rate at 3 Months | Progression-free survival (PFS) rate at 3 months is defined as the number of patients without evidence of progression or death after 3 months from randomisation among the PFS-evaluable patients. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) | Progression-free survival (PFS) defined as the median time from randomization to death from any cause or first observed disease progression. | Performed at baseline, every 4 weeks until Week 12 following randomization and then every 8 weeks until objective disease progression. | 
| Overall Survival (OS) | Overall survival (OS) defined as the median time from randomization to death from any cause. | Every 12 weeks unless the patient withdraws consent | 
| Disease of Response (DOR) | Number of patients showing Complete Response (CR), Partial Response (PR) or Stable Disease (SD) based on RECIST for the best response. Number of patients showing Complete Response (CR, disappearance of all target lesions), Partial Response (PR, at least a 30% decrease in the sum of longest diameter of target lesions taking as reference the baseline sum longest diameter) or Stable Disease (SD, Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as references the smallest sum longest diameter since the treatment started) based on RECIST Criteria Version 1.0 (assessed by CT and/or MRI) for the best response | Performed at baseline, every 4 weeks until Week 12 following randomization and then every 8 weeks until objective disease progression. | 
| Objective Response Rate (ORR) | Number of patients showing Complete Response (CR) or Partial Response (PR) based on RECIST for the best response. Number of patients showing Complete Response (CR, disappearance of all target lesions) or Partial Response (PR, at least a 30% decrease in the sum of longest diameter of target lesions taking as reference the baseline sum longest diameter) based on RECIST Criteria Version 1.0 (assessed by CT and/or MRI) for the best response. | Performed at baseline, every 4 weeks until Week 12 following randomization and then every 8 weeks until objective disease progression. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vandetanib, NSCLC, Maintenance, Phase II