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

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

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.

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.

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.