The primary purpose of this study is to find the highest tolerated dose of the study drugs capecitabine, oxaliplatin, bevacizumab, and dasatinib given in combination to subjects with advanced solid tumors. This will occur in the first part of the study (Phase I).

Once this dose has been determined, it will be given to subjects with advanced metastatic colorectal cancer in the second part of the study (Phase II).

By giving these drugs in combination, researchers hope to evaluate the side effects of the study drugs in both groups, and to determine if this combination could possibly decrease or stabilize the cancer being treated.

Subjects will be enrolled at Duke University Medical Center (DUMC) and Rocky Mountain Cancer Center.

After satisfying eligibility and screening criteria, patients will be treated on 21 day cycles.

Eligibility

You must be at least 18 years old to participate in this study.

Inclusion Criteria for All Participants 

To participate in this study, patients must meet the following criteria:

• Karnofsky performance status > 70 percent
• Life expectancy of at least three months
• Adequate organ and marrow function
• Sexually active women of childbearing potential must use an effective method of birth control during the course of the study and must have a negative pregnancy test within seven days prior to first receiving the study drugs
• Ability to understand and the willingness to sign a written informed consent document

Criteria Specific for Dose Escalation (Phase I)

To participate in Phase I of this study, patients must:

• Have a histologically confirmed solid tumor malignancy that is metastatic or unresectable
• Standard curative or palliative measures do not exist or are no longer effective in treating their tumors
• Capecitabine, oxaliplatin, and/or bevacizumab are considered a standard therapy or therapeutic option to treat their tumors

Criteria Specific for Expanded Cohort Portion of Trial Only (Phase II)

To participate in Phase II of this study, patients must:

• Have a histologically documented adenocarcinoma of the colon or rectum that is a metastatic or recurrent disease
• No prior chemotherapy for metastatic/recurrent colorectal cancer. Patients may have received a radiosensitizing dose of 5-fluorouracil or capecitabine for the treatment of local disease in the localized or metastatic setting
• No history of other carcinomas within the last five years, except cured non-melanoma skin cancer, curatively treated in-situ cervical cancer, or localized prostate cancer
• Disease must be measurable by RECIST criteria

Exclusion Criteria for All Subjects

• Patients who have had radiation therapy, hormonal therapy, biologic therapy, or chemotherapy for cancer or any other investigational agents within the 28 days prior to the first day of study drug treatment
• Patients with known CNS metastases
• Inadequately controlled hypertension or prior history of hypertensive crisis or hypertensive encephalopathy
• Significant vascular disease (e.g., aortic aneurysm, aortic dissection) or symptomatic peripheral vascular disease
• Evidence of bleeding diathesis or coagulopathy. Patients on full-dose anticoagulation are permitted to enroll provided that they have been clinically stable on anti-coagulation
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to day one of study drug treatment 
• Core biopsy or other minor surgical procedure excluding placement of a vascular access device, within seven days prior to expected start of treatment
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within six months prior to day one of the study
• Serious, non-healing wound, ulcer, or bone fracture 
• Proteinuria at screening 
• New York Heart Association (NYHA) Grade II or greater congestive heart failure
• History of myocardial infarction, unstable angina, cardiac or other vascular stenting, or angioplasty
• History of stroke or transient ischemic attack within six months prior to day one of the study treatment
• History of intolerance or hypersensitivity to prior treatment with capecitabine, oxaliplatin, bevacizumab, and/or dasatinib
• No previous treatment with dasatinib
• Prior unanticipated severe reaction to fluoropyrimidine therapy, or known hypersensitivity to 5-fluorouracil, or known DPD (dihydropyrimidine dehydrogenase) deficiency
• Patient with grade two or greater peripheral neuropathy
• Chronic treatment with systemic steroids or another immunosuppressive agent
• Other concurrent severe and/or poorly controlled medical condition that could compromise safety of treatment as so judged by treating physician
• Known history of HIV seropositivity,hepatitis C virus, acute or chronic active hepatitis B infection, or other serious chronic infection requiring ongoing treatment
• Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter drug absorption (e.g., inflammatory bowel disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or significant small bowel resection)
• Patients unwilling to or unable to comply with the protocol
• Diagnosed or congenital long QT syndrome 
• Any history of clinically significant ventricular arrhythmias
• Prolonged QTc interval on pre-entry electrocardiogram (> 450 msec) 
• Pleural effusion grade > two
• Patients currently taking drugs that are generally accepted to have a risk of causing Torsades de Pointes
• History of significant bleeding disorder unrelated to cancer 
• Patients actively taking proton pump inhibitors or H2 antagonists will be excluded from this study
• Any psychiatric illness/social situations that would limit safety or compliance with study requirements
• Medications that inhibit platelet function (except low dose aspirin as defined in study protocol) 
• Use of medications that are either CYP3A4 inhibitors or inducers

For more information, contact the clinical research coordinator at 919-668-1861.