Dasatinib in Combination With Bevacizumab to Treat Advanced Solid Tumors

Completed · Phase 1

Conditions studied: Solid Tumors

In brief

Background: * Bevacizumab inhibits blood vessel growth in cancer cells by blocking a growth factor called VEGF. Dasatinib inhibits the action of proteins called tyrosine kinases, which promote and stimulate blood vessel formation and cancer growth and spread. * Using the two drugs in combination may provide a more effective cancer treatment than either drug used alone. * Both drugs have been approved by the Food and Drug Administration for different cancer types, but their use in combination sis experimental. Objectives: \- To determine the highest doses of the combination of dasatinib and bevacizumab that can be safely given to patients with different cancers and to find out what effects, good and bad, these drugs may have on the patient and the disease. Eligibility: \- Adult patients with an advanced solid tumor cancer that cannot be treated successfully with standard therapies. Design: * Patients in Group 1 receive dasatinib and bevacizumab together throughout the study. The dose is increased in successive groups of three to six patients until the optimum safe dose is determined. Patients take dasatinib by mouth once a day and receive bevacizumab as an infusion through a vein once every 2 weeks in 28-day treatment cycles. * Patients in Group 2 are randomly assigned to receive either dasatinib or bevacizumab for cycle one, and then both drugs for all subsequent cycles. The drug doses are based on the optimum doses found in Group 1 patients. * Patients have a physical examination and blood and urine tests every 2 weeks for cycles 1 and 2, and then every 4 weeks for the duration of treatment. * Patients have CT or MRI scans or another imaging test such as ultrasound every 8 weeks to monitor the cancer s response to treatment. * Tumor biopsies are obtained from patients in Group 2 before treatment, 2 weeks into the first treatment cycle, and 2 weeks into the second cycle. * Dynamic, contrast-enhanced MRI (DCE-MRI) tests are done on patients in Group 2 before treatment, 2 weeks into the first cycle and 4 weeks into the second cycle. This MRI test uses a special non-radioactive dye that shows blood flow in a certain part of the body. * For patients who have been on the study over 2 years, the cycle may be lengthened to 6 or 8 weeks at the discretion of the investigator.

Key facts

Study ID

NCT01445509

Run by

National Cancer Institute (NCI)

People needed

50

Starts

2008-12-29

Expected to finish

2018-09-20

Last updated by the study team

2026-08-07

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may not qualify if…

• Brain metastases
• Patients who have a history of remote CNS metastases that have undergone "curative therapy" by radiation therapy, gamma knife therapy, or surgery and have remained without recurrence for a period of >=6 months will be eligible.
• CNS imaging will not be mandated for all patients. However, if there is clinical suspicion of CNS involvement, a contrast CT or MRI of the brain will be required. Screening CNS scans should be required for certain tumor types with relatively high risk of CNS metastases, including but not limited to melanoma, renal cell carcinoma, breast, lung.
• Thrombotic or embolic events within the past 6 months such as a cerebrovascular accident (including transient ischemic attacks), pulmonary embolism, unstable angina, or myocardial infarction. Patients with recent (< 3 month history) of venous thrombotic events will be considered on a case by case basis.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (AHA Class II or worse), unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• 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.
• QTc prolongation (defined as a QTc interval equal to or greater than 480 msecs) or other clinically significant EKG abnormalities
• Patients may not have any clinically significant cardiovascular disease including the following:
• Myocardial infarction or ventricular tachyarrhythmia within 6 months
• Prolonged QTc >= 480msec (Fridericia correction)
• 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)
• Patients who have an active pleural effusion may be considered if tapped prior to study. Patients with pleural effusions that are too small to be removed may be considered on a case by case basis. Patients with a Grade 2, asymptomatic pericardial effusion found incidentally on imaging studies may be considered on a case by case basis.
• Dasatinib is metabolized primarily by the CYP3A4 liver enzyme. Consideration should be given to using alternative medications not impacting CYP3A4 while on dasatinib therapy.
• Patients may not be receiving any prohibited potent CYP3A4 inhibitors. For these drugs, a wash-out period of >= 7 days is required prior to starting dasatinib treatment.
• Category I drugs that are generally accepted to have a risk of causing Torsades de Pointes. A wash-out period of >= 7 days is required for the following drugs prior to starting dasatinib treatment:
• Quinidine, procainamide, disopyramide
• Amiodarone, sotalol, ibutilide, dofetilide
• Erythromycin, clarithromycin
• Chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide
• Cisapride, bepridil, droperidol, methadone, arsenic, chlorquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine
• HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with dasatinib, bevacizumab, and/or the combination. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
• Patients who have been treated with dasatinib (or any other Src-family kinase inhibitors) will be excluded
• Hypertension defined as systolic blood pressure >140 mmHg or diastolic pressure >= 90 mmHg despite optimal medical management.
• Proteinuria defined as a spot urine analysis for protein creatinine ratio (UPC) of > 1.0

Where it is running

• National Institutes of Health Clinical Center — Bethesda, Maryland, United States

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.