Pilot Study of Bisphosphonate Therapy (Zoledronic Acid) in Patients With Malignant Mesothelioma (UAB 0901)

Study Overview
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Brief Summary
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The primary objective of this trial is to determine the response rate of single agent zoledronic acid using a composite of criteria including the EORTC modified RECIST criteria and the EORTC tumor response criteria for 18F-FDG PET scans.

Detailed Description
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This pilot study will examine the effect of bisphosphonate (zoledronic acid) in patients with malignant mesothelioma. Evaluation will be limited to patients with standard (CT scans) and functional instruments (FDG PET Scans) of tumor assessment after the administration of standard doses of zoledronic acid (4 mg IV every 3 weeks). We will also explore the biologic effect of zoledronic acid in patients using new serum markers as well as several blood level markers.

Official Title
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A Pilot Phase 2 Study of Bisphosphonate Therapy (Zoledronic Acid) in Patients With Advanced Malignant Mesothelioma

Conditions
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Mesothelioma

Intervention / Treatment
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* Drug: Zometa


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females > 18 years of age Life expectancy of at least 2 months Histologically confirmed unresectable malignant pleural mesothelioma (MPM) Measurable disease by CT Scan criteria and/or positive metabolic activity of 18F-FDG PET Scan criteria at screening ECOG Performance Status of 0-2 Laboratory and clinical results within 2 weeks prior to Day 1 must be as follows: ANC ≥ 1.5 x 109/L Platelet Count ≥ 100 x 109/L Hemoglobin ≥ 9g/dL Serum bilirubin ≤ 1.5 x upper limit of normal (ULN) AST ≤ 2.5 x ULN ALT ≤ 2.5 x ULN ALK-P ≤ 3 x ULN Serum creatinine ≤ 1.8mg/dL Calculated Serum Creatinine Clearance 40 - > 60ml/min Female subjects of childbearing potential and all male subjects must be surgically sterile or consent to use a medically acceptable method of contraception throughout the trial. Willing and able to provide written informed consent. Exclusion Criteria: Known central nervous system (CNS) tumor involvement Evidence of other active malignancy requiring treatment Clinically significant heart disease (e.g., congestive heart failure of New York Heart Association Class 3 or 4 angina not well controlled by medication, or myocardial infarction within 6 months) Known infection with HIV or hepatitis Clinically significant arrhythmias demonstrated on electrocardiogram (ECG). Note: subjects with chronic atrial arrhythmia, i.e., atrial fibrillation or paroxysmal supraventricular tachycardia (SVT) are eligible. Active, serious systemic disease, including active bacterial or fungal infection. Subjects undergoing invasive dental procedures, significant periodontal disease or history of osteonecrosis of the jaw. Treatment within 4 weeks of the start of the trial with other systemic anticancer therapy. Breastfeeding, pregnant, or likely to become pregnant during the clinical trial.

Ages Eligible for Study
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Minimum Age: 19 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Zometa<br>Zometa (zoledronic acid) will be administered by infusion on Day 1 of a 3-week cycle followed by tumor assessment from CT and/or PET scans every 2 cycles. This will continue until progression of disease and/or intolerable toxicity. | Drug: Zometa<br>* Zoledronic acid will be administered IV on the first day of a 21 day cycle at a concentration of 4 mg. The treatment will take about 30-60 minutes with the infusion lasting about 15 minutes.<br>* Other names: Zoledronic acid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor Response Rate Following Zoledronic Acid (Zometa) | The modified Response Evaluation Criteria in Solid Tumors Criteria (RECIST 2004) will be used for target lesions and assessed by CT scans. Complete Response (CR) is the disappearance of target lesions; Partial Response (PR) is greater than or equal to 30% reduction in the total tumor measurement; Stable Disease (SD) is the absence of response or progression; and Progressive Disease (PD) is a 20% increase in the total tumor measurement over nadir value or the appearance of new lesions. | Baseline up to 28 months or until progressive disease or death | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | Progression Free Survival is defined as the number of days from the day the subject started treatment to the day the subject experienced evidence of disease progression, as determined by radiological or clinical progression. | Baseline up to 28 months | 
| Overall Survival (OS) | Overall Survival is defined as the number of days from the day the subject started treatment to the day the subject experienced death or lost to follow-up. | Baseline up to 28 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mesothelioma, zoledronic acid, zometa, bisphosphonate therapy, CT scan, PET scan