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Investigator(s):
Elise C. Kohn, M.D. Principal Investigator Phone: 301-402-2726 kohne@mail.nih.gov
Referral Contact(s):
Laura D. Otten, R.N., B.S.N., O.C.N. Medical Oncology Referral Coordinator Phone: 301-451-1228 1-866-611-6310 (Toll Free) Fax: 301-480-0919 ottenl@mail.nih.gov	Nicole Houston, B.S.N., R.N. Research Nurse Phone: 301-443-6431 houstonnd@mail.nih.gov

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Key Eligibility Criteria:

• 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
• Patients with pleural effusion may be eligible provided it was tapped prior to study
• No brain metastases (unless treated with “curative therapy” by radiation therapy, gamma knife therapy, or surgery, and no recurrence for ≥ 6 months)
• No squamous cell carcinoma of the lungs or a history of any type of lung cancer and hemoptysis
• Recovered from all prior therapy
• Patients must be off prior chemotherapy, radiation therapy, hormonal therapy, or biological therapy for at least 4 weeks; patients who were receiving mitomycin C, nitrosoureas, bevacizumab, or carboplatin must be 6 weeks from the last administration of chemotherapy
• No prior dasatinib, any other Src-family kinase inhibitors
• No concurrent use of potent inhibitors of CYP3A4
• No concurrent use of known QT-prolonging agents
• Patients with prostate cancer must continue to receive leuteinizing hormone-releasing hormone agonist unless orchiectomy has been performed
• No therapeutic anticoagulation with coumadin, heparins, or heparinoids (prophylaxis doses are permitted)
• No thrombotic or embolic events within the past 6 months (CVA, TIA, pulmonary embolisum, unstable angina, or myocardial infarction); recent history (< 3 months) of venous thrombotic events considered on a case-by-case basis)
• No QTc prolongation (≥ 480 msecs) or other clinically significant EKG abnormalities
• No combination anti-retroviral therapy
• ECOG performance status (PS) 0–1 (PS of 2 is considered on a case-by-case basis)
• Leukocytes > 3,000/µL; ANC > 1,200/µL; platelet count > 100,000/µL; total bilirubin ≤ 1.5 x upper limit of normal (ULN) (in the absence of Gilbert's syndrome); AST and ALT ≤ 2.5 x ULN; creatinine ≤ 1.5 mg/dL OR creatinine clearance > 45 mL/min
• Activated partial thromboplastin time ≤ 1.25 x ULN (in the absence of lupus anticoagulant)
• Prothrombin time OR international normalized ratio ≤ 1.25 x ULN
• Spot urine protein–creatinine ratio ≤ 0.5 OR a 24-hour urine for protein excretion ≤ 1,000 mg
• Not pregnant or nursing; fertile patients must use effective contraception during and for ≥ 3 months after completion of study
• No medical condition that would preclude study participation
• No swallowing impairment that would preclude administration of dasatinib
• No known hypersensitivity to Chinese hamster ovary cell products or recombinant human antibodies

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Study Outline:

This is a dose-escalation study of dasatinib and bevacizumab (Group 1) followed by a randomized study (Group 2). The dose-escalation phase of the study has been completed. Group 2 is now enrolling.

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 one of two 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 undergo tumor biopsies and dynamic contrast-enhanced MRI before drug treatment, after 2 weeks of single agent therapy, and at 6 weeks (after at least 2 weeks of combined therapy)
• Blood samples are collected for future study
• After completion of study therapy, patients are followed for 4 weeks

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Additional Information:

• This trial will be conducted at the NIH Clinical Center in Bethesda, MD. It is open to patients who meet the eligibility requirements, regardless of where they live in the United States.
• There is no charge for medical care received at NIH Clinical Center.
• FAQs about this study - provides information for patients about the trial such as frequency and duration of visits, costs, how to enroll, and study outline.
• PDQ (Physicians Data Query) - provides additional details about this study for health care providers.

Reviewed: 8/24/12
Updated: 7/16/12