Vandetanib and Bevacizumab in Treating Patients With Advanced Solid Tumors or Lymphoma

DISEASE CHARACTERISTICS:

• Histologically confirmed advanced malignancy, including the following:

  • Solid tumor that is refractory to standard therapy or for which no standard therapy exists

    • No lung carcinoma of squamous cell or small cell histology (mixed tumors will be categorized by the predominant cell type)

      • Histological confirmation based on sputum cytology alone is not acceptable
  • Lymphoma (Hodgkin or non-Hodgkin lymphoma) that has progressed after standard therapy AND for which stem cell transplantation is not indicated or has been refused

• No known CNS disease, except for treated brain metastasis meeting the following criteria:

  • No ongoing requirement for steroids

  • No evidence of progression or hemorrhage by clinical examination and brain imaging (MRI or CT scan) for ≥ 3 months after treatment

    • Stable dose of anticonvulsants allowed

  • Prior treatment for brain metastases may have included whole-brain radiotherapy, radiosurgery (gamma knife, linear accelerator, or equivalent), or a combination of therapy as deemed appropriate by the treating physician

    • Neurosurgical resection or brain biopsy for treatment of CNS metastases allowed provided treatment was completed more than 3 months ago

PATIENT CHARACTERISTICS:

• ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
• Life expectancy > 3 months
• Absolute neutrophil count ≥ 1,500/μL
• Platelet count ≥ 100,000/μL
• Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST and ALT ≤ 2.5 times ULN
• Creatinine < 1.5 times ULN OR creatinine clearance ≥ 60 mL/min
• Urine protein:creatinine ratio ≤ 0.5 OR urine protein < 1,000 mg by 24-hour urine collection
• Activated partial thromboplastin time ≤ 1.5 times ULN
• Prothrombin time OR INR < 1.5 times ULN
• Potassium between 4 mmol/L and ULN (supplementation allowed)
• Magnesium normal (supplementation allowed)
• Serum calcium (adjusted for albumin) or ionized calcium normal (supplementation allowed)
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for ≥ 6 months after completion of study therapy

• HIV-positivity allowed provided the following criteria are met:

  • Patient does not require anti-HIV therapy
  • CD4 count > 350/mm^3
  • HIV viral load < 25,000 copies/mm^3
  • No history of opportunistic infections

• No evidence of severe or uncontrolled systemic disease or any concurrent condition that could compromise participation in the study, including any of the following:

  • 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
  • Psychiatric illness/social situation that, in the investigator's opinion, would make it undesirable for the patient to participate in the study or that would jeopardize study compliance
• No New York Heart Association class III or IV heart disease within the past 6 months

• No history of arrhythmia (i.e., multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation) that is symptomatic or requires treatment

  • Atrial fibrillation allowed provided it is controlled with medication
• No asymptomatic sustained ventricular tachycardia
• No other cardiac disease that, in the investigator's opinion, would increase the risk of ventricular arrhythmia
• QTc < 480 msec (with measurable Bazett correction) by screening ECG
• No history of QTc prolongation as a result of other medications that required discontinuation
• No congenital long QT syndrome
• No first-degree relative with unexplained sudden death at under 40 years of age
• No left bundle branch block
• No hypertension not controlled by medical therapy, defined as systolic blood pressure > 150 mm Hg or diastolic blood pressure > 90 mm Hg despite optimal medical management
• No other clinically significant cardiac event
• No thromboembolic disease within the past 6 months
• No significant vascular disease (e.g., aortic aneurysm or aortic dissection) or clinically significant peripheral vascular disease
• No serious non-healing wounds (including wounds healing by secondary intention)
• No acute or non-healing ulcers
• No bone fractures within the past 3 months
• No abdominal fistula, gastointestinal perforation, or intra-abdominal abscess within the past 28 days
• No currently active diarrhea that may affect the ability of the patient to absorb or tolerate vandetanib
• No hemoptysis (bright red blood of ≥ ½ teaspoon per episode) within the past 3 months
• No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Prior anti-VEGF therapy allowed
• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) or radiotherapy and recovered
• More than 4 weeks since prior major surgery and recovered
• At least 2 weeks since prior investigational drugs given in a phase 0 clinical trial
• More than 10 days since prior and no concurrent aspirin (> 325 mg/day) or chronic use of other NSAIDs
• No concurrent regular, therapeutic anticoagulation

• No concurrent medication that may cause QTc prolongation, induce Torsades de Pointes, or induce CYP3A4 function, including any of the following:

  • Rifampin
  • Rifabutin
  • Phenytoin
  • Carbamazepine
  • Phenobarbital
  • Hypericum perforatum (St. John's wort)
• No other concurrent antineoplastic therapy, except for gonadotropin-releasing hormone therapy for prostate cancer