Enzastaurin and Bevacizumab in Treating Patients With Locally Advanced or Metastatic Cancer

DISEASE CHARACTERISTICS:

• Histologic or cytologic diagnosis of locally advanced or metastatic cancer for which no preferable therapy exists
• Measurable or nonmeasurable disease
• No CNS metastases or a primary CNS tumor

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Life expectancy ≥ 12 weeks
• WBC count ≥ 3.0 × 10^9/L
• Absolute neutrophil count ≥ 1.5 × 10^9/L
• Platelet count ≥ 100 × 10^9/L
• Hemoglobin ≥ 10 g/dL (6.21 mmol/L)
• Bilirubin ≤ 2 times upper limit of normal (ULN)
• Alkaline phosphatase ≤ 3 times ULN (5 times ULN if liver metastases are present)
• AST and ALT ≤ 3 times ULN (5 times ULN if liver metastases are present)
• Serum creatinine < 1.5 times ULN
• No proteinuria at baseline, as demonstrated by either of the following:
• Urine protein:creatinine ratio < 1.0 at screening
• Urine dipstick for proteinuria < 2+ (patients discovered to have ≥ 2+ proteinuria on dipstick urinalysis at baseline must undergo a 24-hour urine collection that demonstrates ≤ 1 g of protein in 24 hours to be eligible for study participation)
• No second primary malignancy that could affect compliance with the study or interpretation of the study results
• No concurrent serious systemic disorder (e.g., active infection, including HIV) that, in the opinion of the investigator, would compromise the patient's ability to adhere to the study
• No known hypersensitivity to bevacizumab or enzastaurin hydrochloride, or to a component of either drug
• No prior bevacizumab-related toxicity requiring discontinuation, such as a thromboembolic event, hemorrhage, or serious hypertension
• No clinically significant cardiac disease, in the opinion of the investigator, including any of the following:
• Myocardial infarction within the past 6 months
• Symptomatic angina pectoris
• Congestive heart failure not controlled by medications
• ECG abnormalities indicative of clinically significant cardiac disease
• No evidence of bleeding diathesis or coagulopathy
• No nonhealing cutaneous wound or gastrointestinal ulcer
• No history of or risk for abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
• No hemoptysis requiring medical attention within the past 3 months
• No known history of cerebrovascular accidents or transient ischemic attacks
• No clinically significant vascular or peripheral vascular disease
• No hypertension not controlled by medical management
• No history of hypertensive crisis or hypertensive encephalopathy
• No significant traumatic injury within the past 28 days
• Able to comply with study or study procedures
• Able to swallow tablets
• Exhibits compliance and geographic proximity that allow adequate follow-up
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 3 months after completion of study treatment

PRIOR CONCURRENT THERAPY:

• Recovered from prior therapy
• No prior participation in this study or any other study involving enzastaurin hydrochloride
• At least 4 weeks since prior chemotherapy (6 weeks for mitomycin C or nitrosoureas)
• At least 4 weeks since prior radiotherapy, anticancer hormone therapy, or other investigational therapy
• Patients with hormone-refractory prostate cancer receiving luteinizing hormone-releasing hormone analogue therapy (leuprolide or goserelin) prior to study enrollment should continue therapy during study participation
• At least 6 weeks since prior bicalutamide
• At least 4 weeks since prior flutamide or nilutamide
• More than 10 days since prior and no concurrent aspirin > 325 mg/day
• More than 28 days since prior major surgery or open biopsy
• More than 7 days since prior core biopsy or other minor surgical procedure, excluding placement of a vascular access device
• No concurrent carbamazepine, phenobarbital, or phenytoin
• No concurrent systemic anticoagulation
• No concurrent chronic use of other nonsteroidal anti-inflammatory drugs
• No concurrent routine use of colony-stimulating factors
• No concurrent major surgery
• No other concurrent chemotherapy, radiotherapy, immunotherapy, or experimental medications
• No other concurrent antitumor therapy