INCLUSION CRITERIA:
Patients must have:
-Histologically documented (confirmed at the Laboratory of Pathology, NCI) solid tumors and lymphoid malignancies (HL and NHL).
-Already received standard therapy for their malignancy with disease progression and no other therapies likely to improve their survival. Patients with lymphoid malignancies will be eligible if their disease has progressed following standard therapy and if stem cell transplantation is not indicated or has been refused.
-Age greater than or equal to 18 years.
-Life expectancy of greater than 3 months.
-ECOG performance status less than or equal to 2 (Karnofsky greater than or equal to 60 percent.
-Normal organ and bone marrow function, as defined in the table below:
Normal organ and bone marrow function parameters:
--Absolute neutrophil count- Greater than or equal to 1,500/microL.
--Platelets- Greater than or equal to 100,000/microL.
--Total bilirubin- Less than or equal to 1.5 times institutional upper limit of normal.
--AST (SGOT) and ALT (SGPT)- Less than or equal to 2.5 times institutional upper limit of normal.
--Creatinine- Less than 1.5 times institutional upper limit of normal
or
--creatinine clearance- Greater than or equal to 60 mL/min/1.73 m(2) for patients with creatinine levels greater than or equal to 1.5 times institutional upper limit of normal (calculated by Cockcroft-Gault formula).
--Activated partial thromboplastin time- Less than or equal to 1.5 times institutional upper limit of normal.
--Prothrombin time or INR- Less than 1.5 times institutional upper limit of normal.
--K+ Between 4 and ULN (supplementation allowed).
--Mg+ Within normal limits (supplementation allowed).
-Patients must be able to understand and sign an informed consent form.
-Last dose of chemotherapy or radiation therapy must be over 4 weeks (6 weeks for nitrosoureas and mitomycin C) prior to commencement of this protocol; patients must have recovered from any toxicities related to those treatments to a no more than Grade I CTEP toxicity level (defined by CTCAE v. 3.0). Patients must be greater than or equal to 2 weeks since receiving study drug as a participant in a Phase 0 study.
-Women of childbearing potential must have a negative pregnancy test result. Both fertile men and women must agree to use adequate contraceptive measures (hormonal or barrier method of birth control; abstinence) during study therapy and for at least 6 months after the completion of bevacizumab therapy.
-Patients who have or have not received prior treatment with anti-VEGF therapies may participate.
-HIV-infected patients not requiring anti-HIV therapy with CD4 cells greater than 350/mm(3) and with HIV viral loads less than 25,000 copies/mm(3), and no history of opportunistic infections are eligible to participate.
EXCLUSION CRITERIA:
-Evidence of severe or uncontrolled systemic disease, or any concurrent condition, which could compromise participation in the study, including, but not limited to, active or uncontrolled infection, immune deficiencies, HIV infection requiring anti-HIV therapy, Hepatitis B, Hepatitis C, uncontrolled diabetes, uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction within the past 6 months, uncontrolled cardiac arrhythmia, stroke/cerebrovascular accident within the past 6 months, or psychiatric illness/social situations that in the investigator's opinion would make it undesirable for the patient to participate in the trial, or which would jeopardize compliance with the protocol.
-Clinically significant cardiac events, such as myocardial infarction, New York Heart Association classification of heart disease greater than 2 within 6 months prior to study entry, or presence of cardiac disease that in the investigator's opinion increases the risk of ventricular arrhythmia.
-Significant vascular disease (e.g., aortic aneurysm, history of aortic dissection) or clinically significant peripheral vascular disease.
-History of arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation) that is symptomatic or requires treatment (CTCAE Grade 3), or asymptomatic sustained ventricular tachycardia. Atrial fibrillation controlled with medication is not excluded.
-Therapeutic anticoagulation on a regular basis will also be excluded due to hemorrhage risk. History of thromboembolic diseases in the last 6 months.
-Previous history of QTc prolongation as a result of other medications that required discontinuation. Patients who are receiving a drug that has a risk of QTc prolongation are excluded if QTc is greater than or equal to 460 msec.
-Congenital long QT syndrome, or first degree relative with unexplained sudden death under 40 years of age.
-Presence of left bundle branch block.
-QTc with unmeasurable Bazett's correction or greater than or equal to 480 msec on ECG screening. If a patient has a QTc greater than or equal to 480 msec upon ECG screening, the test may be repeated twice (at least 24 hours apart). The average QTc from the 3 ECGs screenings must be less than 480 msec in order for the patient to be eligible for the study.
-Any concomitant medication that may cause QTc prolongation, induce Torsades de Pointes or induce CYP3A4 function (rifampicin, rifabutin, phenytoin, carbamazepine, phenobarbital and St. John's Wort).
-Hypertension not controlled by medical therapy (hypertension defined as systolic blood pressure greater than 150 mmHg or diastolic pressure greater than 90 mmHg despite optimal medical management).
-Urine protein should be screened by urine analysis for Urine Protein Creatinine (UPC) ratio. For UPC ratio greater than 0.5, 24-hour urine protein should be obtained and the level should be less than 1000 mg for patient enrollment.
Note: UPC ratio of spot urine is an estimation of the 24-hour urine protein excretion - a UPC ratio of 1 is roughly equivalent to a 24-hour urine protein of 1 g. UPC ratio is calculated using on of the following formula:
- [urine protein] / [urine creatinine] - if both protein and creatinine are reported in mg/dL.
- [(urine protein) times 0.088] / [urine creatinine] - if urine creatinine is reported in mmol/L.
-Serious non-healing wounds (including wounds healing by secondary intention), acute or non-healing ulcers, or bone fractures within 3 months of fracture. History of abdominal fistula, GI perforation or intra-abdominal abscess within 28 days will be excluded.
-Currently active diarrhea that may affect the ability of the patient to absorb vandetanib or tolerate vandetanib.
-Women who are currently pregnant or breast feeding.
-Major surgery within 4 weeks, or incompletely healed surgical incision before starting the study therapy.
-Known CNS disease except for treated brain metastasis (defined as having no ongoing requirement for steroids and no evidence of progression or hemorrhage after treatment for at least 3 months, as ascertained by clinical examination and brain imaging [MRI or CT]. Stable dose of anticonvulsants are allowed). Treatment for brain metastases may include whole brain radiotherapy (WBRT), radiosurgery (RS; Gamma Knife, LINAC, or equivalent) or a combination as deemed appropriate by the treating physician. Patients with CNS metastases treated by neurosurgical resection or brain biopsy performed within 3 months prior to Day 1 will be excluded.
-Lung carcinoma of squamous cell histology (mixed tumors will be categorized by the predominant cell type unless small cell elements are present, in which case the patient is ineligible; sputum cytology alone is not acceptable). Also excluded are patients with a history of hemoptysis (bright red blood of 1/2 teaspoon or more per episode) within 3 months prior to study enrolment and current or recent (within 10 days of enrollment) use of aspirin (less than 325 mg/day) or chronic use of other NSAIDs.
-Serum calcium above the CTCAE Grade 1 upper limit. In cases where the serum calcium is below the normal range, 2 options would be available: 1) the calcium adjusted for albumin is to be obtained and substituted for the measured serum value. Exclusion is to then be based on the adjusted for albumin values falling below the normal limit. 2) Determine the ionized calcium levels. Exclusion is then to be based if these ionized calcium levels are out of normal range despite supplementation.
-Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies.