A Study to Evaluate the Safety and Efficacy of Zoledronic Acid in the Prevention or Delaying of Bone Metastasis in Patients With Stage IIIA and IIIB Non-small Cell Lung Cancer (NSCLC)

Study Overview
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Brief Summary
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30-40% of patients with lung cancer will develop bone metastases during the course of their disease, which can lead to pain, decreased mobility and skeletal complications. This study will investigate the effect of zoledronic acid on preventing or delaying the development of bone metastases and the impact on disease progression/survival in patients with stage IIIA and IIIB Non-small Cell Lung Cancer (NSCLC).

Official Title
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A Study to Evaluate the Safety and Efficacy of Zoledronic Acid in the Prevention or Delaying of Bone Metastasis in Patients With Stage IIIA and IIIB Non-small Cell Lung Cancer

Conditions
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Non-Small-Cell Lung Cancer

Intervention / Treatment
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* Drug: Zoledronic acid 4 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed Non-small Cell Lung Cancer (NSCLC) Newly Diagnosed, Stage IIIA and Stage IIIB excluding patients with pleural effusion Patients must have received primary treatment for their disease and had no progression Exclusion Criteria: Diagnosed with NSCLC longer than 6 months ago Treatment with other bisphosphonates in past 12 months Presence of metastases Other protocol-defined inclusion and exclusion criteria may apply.

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Zoledronic acid<br>Zoledronic acid 4 mg intravenous infusion over at least 15 minutes every 3 to 4 weeks for 24 months. Dosage was adjusted for participants with mild or moderate renal impairment. | Drug: Zoledronic acid 4 mg<br>* Zoledronic acid 4 mg in 5 mL concentrated solution prepared with 100 mL calcium free infusion solution (0.9 % sodium chloride or 5% glucose solution).<br>* Other names: Zometa®;|
| Other: Control<br>No investigational treatment. If a participant developed bone metastases, treatment was started with Zoledronic acid 4 mg intravenous infusion over at least 15 minutes every 3 to 4 weeks until 24 months from the date of study entry had elapsed. | Drug: Zoledronic acid 4 mg<br>* Zoledronic acid 4 mg in 5 mL concentrated solution prepared with 100 mL calcium free infusion solution (0.9 % sodium chloride or 5% glucose solution).<br>* Other names: Zometa®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival | Progression-free survival is defined as the time from randomization to the date of the first documented progression or recurrence of disease or death from any cause. Time to disease progression (TTP) was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines with evaluations every 3 months. | Up to 24 months | 
| Kaplan-Meier Estimates for Progression-free Survival | Progression-free survival is defined as the time from randomization to the date of the first documented progression or recurrence of disease or death from any cause. Time to disease progression (TTP) was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines with evaluations every 3 months. | Months 6, 12, 18, and 24 | 
| Percentage of Participants With Progression-Free Survival Events | Percentage of Participants with the Progression-free survival events: disease progression and death. Time to disease progression (TTP) was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines with evaluations every 3 months. | Up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Bone Metastases at 6, 12, 18, and 24 Months | Percentage of participants developing at least 1 bone metastasis, whether or not symptomatic. Bone scans were scheduled at screening and at 6-monthly intervals after study entry, or when symptoms suggested the presence of bone metastases. Positive bone scans required confirmation by x-ray, magnetic resonance imaging (MRI), or computed tomography (CT). | Months 6, 12, 18 and 24 | 
| Kaplan-Meier Estimate of the Time to Occurrence of Bone Metastases | Time to occurrence of bone metastases was defined as the time from randomization to the date of the first documented bone metastases which could be asymptomatic or symptomatic at the time of detection. Bone scans were scheduled at screening and at 6-monthly intervals after study entry, or when symptoms suggested the presence of bone metastases. Positive bone scans required confirmation by x-ray, magnetic resonance imaging (MRI), or computed tomography (CT). | Months 6, 12, 18, and 24 | 
| Percentage of Participants With Skeletal Related Events (SREs) at 12 and 24 Months From Study Entry | Skeletal Related Events were defined as radiation therapy or surgery to bone, spinal cord compression event or a pathologic bone fracture event. | Months 12 and 24 | 
| Kaplan-Meier Estimates of the Time to the First Skeletal Related Event (SRE) | Time to the first skeletal related event defined as the time from randomization to the date of occurrence of the first SRE. Skeletal Related Events were defined as radiation therapy or surgery to bone, spinal cord compression event or a pathologic bone fracture event | Months 6,12, 18, and 24 | 
| Kaplan-Meier Estimates for Overall Survival |  | Months 6, 12, 18, and 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-Small-Cell Lung Cancer, Bisphosphonates, Zoledronic acid, Bone metastases, Prevention of bone metastases