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

Inclusion Criteria

• •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