A Phase II Study of Novel Oral Anti-Angiogenic Agent AZD2171 (NSC-732208) in Malignant Pleural Mesothelioma

Pts must have unresectable malignant pleural mesothelioma, histologically confirmed, epithelial, sarcomatous or biphasic; Pts must have measurable disease per RECIST cirteria and evidence of disease by CT or MRI; Pts must have had only one treatment regimen prior systemically administered platinum-based chemotherapy (no pleural washing), completed >/= 28 days (42 days for nitrosureas or mitomycin C) and have recovered from associated adverse events; Only one prior chemo regimen is allowed; At least 28 days from any prior surgery (not including minor surgeries) and recovered from all associated toxicities; Pts may have received prior monoclonal antibody therapy against VEGFR, VEGFR1 or VEGFR2; Systolic B/P </= 150 and diastolic B/P </= 100; Pts on stable antihypertensive therapy and with BP w/in this range are eligible; WBC >/= 3,000, ANC >/= 1,500 and platelet count >/= 100,000, serum bilirubin </= IULN, SGOT or SGPT </= 2.5 x IULN; serum creatinine </= IULN or measured CrCl >/= 50 mL/min; Pts must not have prior malignancy except; treated basal cell or squamous cell skin ca, in situ cervical, Stage I or II ca in complete remission; disease-free from any ca for 5 yrs; Pts must have an EKG performed </= 14 days with mean QTc > 470 msec (with Bazett's correction); Pts at increased risk for LVEF dysfunction must have EKG, ECHO/MUGA and troponins </= 14 days ; Pts must not have a history of familial long QT syndrome; Pts must not have GI tract disease resulting in an inability to take oral meds or a requirement for IV alimentation, prior surgical procedures affecting absorption, active peptic ulcer disease; unable to swallow and/or receive enteral meds via g-tube; intractable nausea or vomiting; Pts with 0-1+ proteinuria are eligible. Pts must not have proteinuria >1+ on two consecutive dipsticks no less than 1 week apart; Pts must not have prior treatment with a TKI against VEGFR1 and/or VEGFR2 or prior immunotherapy or biologic therapy; Pts must not have Zubrod PS > 2; < 18 years of age; Pts must not be HIV+ and receiving combination anti-retroviral therapy; Pts must not have known CNS metastases; pts must not be NYHA Class III or IV; Pts must not require concurrent use of proarrhythmics; Pts must not be pregnant or nursing or of reproductive potential and not agreed to use effective contraceptive method; Institutions must have IRB approval of S9925 and pts must be offered participation in S9925. Register pts separately to receive institutional credit for specimen submissions.