A Phase I/Randomized Phase II Study of Cediranib (NSC#732208) Versus Placebo in Combination With Cisplatin and Pemetrexed in Chemonaive Patients With Malignant Pleural Mesothelioma

Inclusion Criteria:

- Histologically or cytologically confirmed malignant pleural mesothelioma

- Not planning to undergo surgical resection

- Patients must have measurable or non-measurable disease by both RECIST and modified
RECIST criteria for pleural tumors as documented by CT scan; examinations for
assessment of measurable disease must have been completed within 28 days prior to
registration; examinations for assessment of non-measurable disease must have been
performed within 42 days prior to registration; all disease must be assessed and
documented on the RECIST 1.1 and Modified RECIST Baseline Tumor Assessment Form

- Zubrod performance status 0-2

- ANC ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- Hemoglobin ≥ 9.0 g/dL (transfusion allowed)

- Total bilirubin ≤ 1.5 times upper limit of normal (ULN)

- SGOT or SGPT ≤ 2.5 times ULN (≤ 5 times ULN if liver metastases are present)

- Serum creatinine ≤ 1.5 times ULN

- Creatinine clearance ≥ 60 mL/min

- Proteinuria ≤ +1 on 2 consecutive dipsticks taken ≥ 7 days apart

- Repeat urinalysis not required provided first urinalysis shows no protein

- Not pregnant or nursing

- Fertile patients must agree to use effective contraception

- Must be able to swallow oral medications

- No mean QTc > 500 msec (with Bazett correction) by ECG or other significant ECG
abnormality

- No NYHA class III-IV congestive heart failure

- No clinically significant hemoptysis, defined as > 1 tablespoon of bright red blood,
within the past year

- No known HIV infection

- No other malignancy within the past 5 years except for adequately treated basal cell
or squamous cell skin cancer, in situ cervical cancer, or adequately treated stage I
or II cancer from which the patient is currently in complete remission.

- No other concurrent chemotherapy, hormonal therapy, radiotherapy, immunotherapy or
any other type of therapy for treatment of cancer

- No prior systemic therapy (chemotherapy or other biological therapy) for unresectable
malignant pleural mesothelioma

- Prior systemicchemotherapy or biologic therapy as neoadjuvant or adjuvant
therapy allowed provided disease has recurred and systemic therapy was completed
> 6 months before study entry

- No prior therapy with any of the study drugs

- At least 28 days since prior surgery (e.g., pleurectomy, pleurodeses, thoracic or
other major surgeries) and recovered

- At least 28 days since prior radiotherapy and recovered

- No concurrent medication that may markedly affect renal function (e.g., vancomycin,
amphotericin, pentamidine)

- No concurrent drugs or biologics with proarrhythmic potential

- No concurrent major surgery