• Safety and toxicity [ Designated as safety issue: Yes ]
• Maximum tolerated dose [ Designated as safety issue: Yes ]
• Biochemical changes in Src-FAK, Src-PLC-γ, and VEGF signal transduction pathways in tumor and stromal cells in response to treatment (Group 2) [ Designated as safety issue: No ]

• Efficacy of this regimen [ Designated as safety issue: No ]
• Correlations between pathway alteration and clinical events [ Designated as safety issue: No ]
• Correlations between clinical outcomes and changes in VEGF and other angiogenic cytokines in plasma and circulating endothelial cells [ Designated as safety issue: No ]
• Application of dynamic contrast-enhanced MRI in determining early changes in tumor vascularity during treatment [ Designated as safety issue: No ]

RATIONALE: Dasatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of solid tumors by blocking blood flow to the tumor. Giving dasatinib together with bevacizumab may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of dasatinib given together with bevacizumab in treating patients with solid tumor that is metastatic or cannot be removed by surgery.

OBJECTIVES:

Primary

• To describe the safety and toxicity of the combination of dasatinib and bevacizumab in patients with advanced solid tumors that have progressed on standard therapy.
• To find the maximum tolerated dose or recommended phase II dose of this combination.
• To describe the biochemical changes in the Src-FAK, Src-PLC-γ, and VEGF signal transduction pathways in tumor and stromal cells in response to treatment. (Group 2)

Secondary

• To determine, preliminarily, the efficacy of this regimen.
• To evaluate correlations between pathway alteration and clinical events.
• To evaluate correlations between clinical outcomes and changes in VEGF and other angiogenic cytokines in plasma and circulating endothelial cells.
• To evaluate the application of dynamic contrast-enhanced MRI in determining early changes in tumor vascularity during treatment.

OUTLINE: This is a dose-escalation study of dasatinib and bevacizumab (group 1) followed by a randomized study (group 2).

• Group 1: Patients receive oral dasatinib once daily on days 1-28 and bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

• Group 2: Patients receive dasatinib and bevacizumab at the maximum tolerated dose determined in group 1. Patients are randomized to 1 of 2 treatment arms.

  • Arm I: In course 1, patients receive oral dasatinib alone once daily on days 1-28. Beginning in course 2 and for all subsequent courses, patients receive oral dasatinib once daily on days 1-28 and bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
  • Arm II: In course 1, patients receive bevacizumab IV over 30-90 minutes on days 1 and 15. Beginning in course 2 and for all subsequent courses, patients receive oral dasatinib once daily on days 1-28 and bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Patients in group 2 undergo tumor biopsies and dynamic contrast-enhanced MRI at baseline, after 2 weeks of single-agent therapy, and after ≥ 2 weeks of combined therapy to examine biochemical effects of treatment and to evaluate changes in vascularity and quality of index lesions. Blood samples are also collected from these patients and archived for future studies, including cytokine and invasion marker analysis and circulating endothelial cell analysis.

After completion of study therapy, patients are followed for 4 weeks.

• Breast Cancer
• Gastrointestinal Stromal Tumor
• Intraocular Melanoma
• Kidney Cancer
• Lung Cancer
• Melanoma (Skin)
• Ovarian Cancer
• Prostate Cancer
• Unspecified Adult Solid Tumor, Protocol Specific

• Biological: bevacizumab
• Drug: dasatinib

• Experimental: In course 1, patients receive oral dasatinib alone once daily on days 1-28. Beginning in course 2 and for all subsequent courses, patients receive oral dasatinib once daily on days 1-28 and bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
• Experimental: In course 1, patients receive bevacizumab IV over 30-90 minutes on days 1 and 15. Beginning in course 2 and for all subsequent courses, patients receive oral dasatinib once daily on days 1-28 and bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

DISEASE CHARACTERISTICS:

• Histologically confirmed metastatic or unresectable malignant solid tumors, including but not limited to, any of the following:

  • Renal cell carcinoma
  • Ovarian cancer
  • Gastrointestinal stromal tumors
  • Melanoma
• Measurable (≥ 1 cm) or evaluable disease
• Standard curative therapies do not exist or are no longer effective

• Patients enrolling in group 2 must have at least one lesion deemed safe to biopsy and be willing to undergo the three mandatory biopsies

  • This determination will be made by a member of the interventional radiology team or surgical associate investigator and an associate investigator

• Patients with pleural effusion are eligible provided it was tapped prior to study

  • Patients with a grade 1 asymptomatic pericardial effusion found incidentally on imaging studies are considered on a case-by-case basis

• No brain metastases

  • Patients who have a history of remote CNS metastases that have undergone curative therapy by radiotherapy, gamma-knife therapy, or surgery and have remained without recurrence for ≥ 6 months are eligible
  • CNS imaging consisting of a contrast CT scan or MRI is only required for patients with certain tumor types with relatively high risk of CNS metastases (including, but not limited to, melanoma, renal cell carcinoma, breast cancer, and lung cancer)
• No squamous cell carcinoma of the lungs or a history of any type of lung cancer and hemoptysis

PATIENT CHARACTERISTICS:

• ECOG performance status (PS) 0-1 (PS of 2 is considered on a case-by-case basis with a focused assessment on risk of perforation)
• Life expectancy > 3 months
• Leukocytes > 3,000/μL
• ANC > 1,200/μL
• Platelet count > 100,000/μL
• Hemoglobin ≥ 10 g/dL
• Total bilirubin ≤ 1.5 times upper limit of normal (ULN) (in the absence of Gilbert's syndrome)
• AST and ALT ≤ 2.5 times ULN
• Creatinine ≤ 1.5 mg/dL OR creatinine clearance > 45 mL/min
• Activated partial thromboplastin time ≤ 1.25 times ULN (in the absence of lupus anticoagulant)
• Prothrombin time OR international normalized ratio ≤ 1.25 times ULN

• Spot urine protein:creatinine ratio ≤ 0.5 OR 24-hour urine for protein excretion ≤ 1,000 mg

  • No proteinuria defined as a spot urine protein-creatinine ratio of > 1.0 g
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for ≥ 3 months after completion of study therapy

• No thrombotic or embolic events within the past 6 months, including any of the following:

  • Cerebrovascular accident (including transient ischemic attacks)
  • Pulmonary embolism
  • Unstable angina pectoris
  • Myocardial infarction
• Patients with recent (i.e., within the past 3 months) venous thrombotic events are considered on a case-by-case basis

• No concurrent uncontrolled illness including, but not limited to, any of the following:

  • Ongoing or active infection

    • Patients with evidence of active infection must have completed antibiotic therapy and be without clinical or laboratory evidence of infection for seven days after treatment has concluded
  • Symptomatic congestive heart failure AHA class II-IV disease
  • Cardiac arrhythmia
  • Psychiatric illness or social situations that would limit compliance with study requirements
• No QTc prolongation (QTc interval ≥ 480 msec [Fridericia correction]) or other clinically significant EKG abnormalities

• No clinically significant cardiovascular disease including any of the following:

  • Ventricular tachyarrhythmia within the past 6 months
  • Ejection fraction less than institutional normal (should be done if clinically indicated and for patients with congestive heart failure on medication)
  • Major conduction abnormality (unless a cardiac pacemaker is present)
• No hypertension defined as systolic BP > 140 mm Hg or diastolic BP > 90 mm Hg despite optimal medical management
• No serious non-healing wounds (including wounds healing by secondary intention), acute or non-healing ulcers, or bone fractures within 3 months of fracture
• No abdominal fistula, bowel obstruction, or intra-abdominal abscesses within the past 28 days
• No hemoptysis within the past 28 days
• No history of gastrointestinal perforation
• No history of high-grade varices
• No evidence of bleeding diathesis
• No swallowing impairment that would preclude administration of dasatinib
• No known hypersensitivity to Chinese hamster ovary cell products or recombinant human antibodies

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Recovered from toxicity related to prior therapy
• No prior dasatinib, any other Src-family kinase inhibitors, or bevacizumab

• At least 4 weeks since prior chemotherapy, radiotherapy, hormonal therapy, or biological therapy

  • At least 6 weeks since prior mitomycin C, nitrosoureas, or carboplatin
• At least 4 weeks since prior therapy with a monoclonal antibody
• At least 28 days since prior major surgery
• At least 7 days since prior and no concurrent herbal supplements
• No concurrent use of potent inhibitors of CYP3A4
• No concurrent use of known (i.e., Class I) QT-prolonging agents

• No other concurrent investigational agents or anticancer agents including hormonal therapy (except for bisphosphonates or erythropoietin analogs)

  • Patients with prostate cancer must continue to receive leuteinizing-hormone releasing-hormone agonist unless orchiectomy has been performed
• No concurrent anti-retroviral therapy for HIV-positive patients
• No concurrent complementary or alternative therapy
• No therapeutic anticoagulation with coumadin, heparins, or heparinoids (prophylaxis doses are permitted)