An Open-Label, Sequential Cohort Dose-Escalation Safety, Tolerability And Pharmacokinetic Study Of VEGF Trap In Patients With Incurable, Relapsed Or Refractory Solid Tumors Or Lymphoma
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed incurable primary or metastatic solid tumor or non-Hodgkin's
lymphoma
- Relapsed after or is refractory (e.g., unresectable) to at least 2 standard
chemotherapy regimens and rituximab
- No standard curative surgery, chemotherapy, immunotherapy, other antitumor
therapy, or radiotherapy options exist
- No known or suspected squamous cell carcinoma of the lung
- No prior or concurrent CNS (brain or leptomeningeal) metastases
- No prior or concurrent primary intracranial tumor by MRI or CT scan
PATIENT CHARACTERISTICS:
Age:
- 25 and over
Performance status:
- ECOG 0-2
Life expectancy:
- Not specified
Hematopoietic:
- WBC at least 3,500/mm^3
- Absolute neutrophil count at least 1,500/mm^3
- Platelet count at least 100,000/mm^3
- Hemoglobin at least 9.0 g/dL
- No other severe or uncontrolled hematologic condition
Hepatic:
- Bilirubin no greater than 1.5 times upper limit of normal (ULN)
- AST and ALT no greater than 2 times ULN
- Alkaline phosphatase no greater than 2 times ULN
- PT, PTT, and INR normal
Renal:
- Creatinine no greater than ULN
- No 1+ or greater proteinuria
- No other severe or uncontrolled renal condition
Cardiovascular:
- Electrocardiogram normal
- LVEF normal by echocardiogram or MUGA scan within the past 12 months or since
completion of prior anthracycline
- No severe or uncontrolled cardiovascular condition
- No New York Heart Association class III or IV heart disease
- No active coronary artery disease, angina, congestive heart failure, or arrhythmia
- No myocardial infarction within the past 6 months
- No prior or concurrent peripheral vascular disease, including:
- Angiographically or ultrasonographically documented arterial or venous occlusive
event
- Symptomatic claudication
- No untreated or uncontrolled hypertension
- No treated blood pressure more than 160/100 mm Hg on at least 3 repeated
determinations on separate days within the past 6 weeks
- No symptomatic orthostatic hypotension
Pulmonary:
- No severe or uncontrolled pulmonary condition
- No pulmonary embolism
Other:
- No prior hypersensitivity reactions to any recombinant proteins (e.g., VEGF Trap)
- No severe or uncontrolled gastrointestinal, immunological, or musculoskeletal
condition
- No severe or uncontrolled psychiatric or adverse social circumstance that would
preclude study
- No active infection requiring antibiotics
- HIV negative
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective double-barrier contraception during and for at
least 3 months after study
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- See Disease Characteristics
- At least 3 weeks since prior immunotherapy
- No concurrent epoetin alfa, filgrastim (G-CSF), or sargramostim (GM-CSF)
Chemotherapy:
- See Disease Characteristics
- At least 3 weeks since prior chemotherapy
Endocrine therapy:
- No concurrent adrenal corticosteroids, except low doses as replacement therapy in
patients who have previously received suppressive doses or for adrenal insufficiency
- No concurrent systemic hormonal contraceptive agents
Radiotherapy:
- See Disease Characteristics
- At least 3 weeks since prior radiotherapy
Surgery:
- See Disease Characteristics
- At least 3 weeks since prior surgery (except fine needle biopsy/aspiration or
removal/biopsy of a skin lesion)
- No prior surgical procedure for correction or prophylaxis of peripheral vascular
insufficiency or cerebral ischemic events
Other:
- Recovered from prior therapy
- At least 6 months since prior treatment for acute congestive heart failure
- At least 30 days since prior investigational drugs
- No concurrent standard or other investigational anticancer agents
- No concurrent herbal supplements ("nutraceuticals")
- No concurrent anticoagulant or antiplatelet drugs, (e.g., warfarin, heparin, aspirin,
or other non-steroidal anti-inflammatory drugs) except selective cyclo-oxygenase-2
(COX-2) inhibitors for analgesia
- No concurrent COX-2 inhibitors for tumor treatment or prophylaxis