Phase I/II Trial of Carboplatin, Bevacizumab and Pemetrexed in the First-Line Treatment of Patients With Malignant Pleural Mesothelioma (MPM)

Inclusion Criteria:

- Patient must have histologically proven diagnosis of Malignant Pleural Mesothelioma
(MPM)

- Patient must have MPM with measurable disease.

- Patients must have Eastern Cooperative Oncology Group (ECOG) performance status of 0,
1, or 2.

- Patient must have adequate renal function with a serum creatinine level of less than
1.5 mg/dl and patient should have a calculated creatinine clearance of more than
40ml/min.

- Patient must have adequate hepatic function with a serum bilirubin level of less that
3mg/dl, and an alkaline phosphatase, ALT and AST of less than five times the upper
limit of normal

- Patient must also have evidence of adequate bone marrow function with an absolute
neutrophil count of more than 1500 cells per deciliter and a platelet count of more
than 100,000 per deciliter.

- Patients must be more than 28 days since prior open biopsy; more than 7 days since
prior fine-needle aspiration; more than 7 days since prior core biopsy; more than 28
days since prior surgery.

- Patients must be able to take dexamethasone, folic acid, and vitamin B-12
supplementation.

- All patients must sign informed consent that will detail the investigational nature
of the study in accordance with the institutional and federal guidelines.

- Patients with clinically significant pleural effusions or ascites (symptomatic or
detectable by clinical exam) should have their effusions drained prior to enrollment
on the clinical trial.

Exclusion Criteria:

- Patients with hypercalcemia (corrected calcium of more than 11 mg/dl) will be
excluded.

- Patients with history of hemoptysis, haematemesis, coagulopathy or thrombosis will be
excluded.

- Patients requiring anticoagulation for any reason will be excluded.

- History of palliative radiation therapy within 2 weeks

- Blood pressure of >160/100 mmHg, despite adequate anti-hypertensive use.

- Currently ongoing unstable angina

- New York Heart Association (NYHA) Grade II or greater congestive heart failure.

- History of stroke within 6 months

- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
prior to the day of initiation of treatment, anticipation of need for major surgical
procedure during the course of the study

- Minor surgical procedures such as fine needle aspirations or core biopsies within 7
days prior to the day of initiation of treatment.

- Pregnant (positive pregnancy test) or lactating

- Urine calculated creatinine clearance of less than 40ml/minute. - History of
abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6
months prior to Day 0

- Serious, non-healing wound, ulcer, or bone fracture

- Inability to comply with study and/or follow-up procedures

Laboratory Values:

- Patient must have adequate renal function with a serum creatinine level of less than
1.5 mg/dl and patient should have a calculated creatinine clearance of more than
40ml/min.

- Patient must have adequate hepatic function with a serum bilirubin level of less than
3 mg/dl, and an alkaline phosphatase, ALT and AST of less than five times the upper
limit of normal

- Patient must also have evidence of adequate bone marrow function with an absolute
neutrophil count of more than 1, 500 cells per deciliter and a platelet count of more
than 100,000 per deciliter.