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

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:

1. ANC ≥ 1.5 x 109/L

2. Platelet Count ≥ 100 x 109/L

3. Hemoglobin ≥ 9g/dL

4. Serum bilirubin ≤ 1.5 x upper limit of normal (ULN)

5. AST ≤ 2.5 x ULN

6. ALT ≤ 2.5 x ULN

7. ALK-P ≤ 3 x ULN

8. Serum creatinine ≤ 1.8mg/dL

9. 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.