Patient case: 58-year-old female with endometrial cancer; genetic feature: PIK3R1

Clinical trial: Intravenous VEGF Trap in Treating Patients With Relapsed or Refractory Advanced Solid Tumors or Non-Hodgkin's Lymphoma

Summary: RATIONALE: VEGF Trap may stop the growth of solid tumors or non-Hodgkin's lymphoma by stopping blood flow to the tumor.
  PURPOSE: This phase I trial is studying the side effects and best dose of intravenous VEGF Trap in treating patients with relapsed or refractory advanced solid tumors or non-Hodgkin's lymphoma.

Detailed description: OBJECTIVES:
  Primary
  -  Determine the safety and tolerability of intravenous VEGF Trap in patients with relapsed or refractory advanced solid tumors or non-Hodgkin's lymphoma.
  Secondary
  -  Determine the maximum tolerated intravenous dose of this drug in these patients.
  -  Determine the pharmacokinetics of this drug in these patients.
  -  Determine the ability of this drug to bind circulating vascular endothelial growth factor in these patients.
  -  Determine, preliminarily, the ability of this drug to alter tumor blood flow and tumor vascular permeability in these patients.
  -  Determine whether antibodies to this drug develop in these patients.
  OUTLINE: This is an open-label, dose-escalation, multicenter study.
  Patients receive VEGF Trap IV over 1 hour on days 1 and 15 for a total of 2 doses.
  Cohorts of 3-6 patients receive escalating doses of VEGF Trap until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, an additional 6 patients are treated at that dose level.
  In the absence of dose-limiting toxicity, patients with stable disease or partial or complete remission may continue to receive VEGF Trap on a separate extension protocol.
  Patients are followed at weeks 1, 3, and 7 and then at 3 months.
  PROJECTED ACCRUAL: A maximum of 25 patients will be accrued for this study.

Eligibility: DISEASE CHARACTERISTICS:
  -  Histologically confirmed diagnosis of one of the following:
  -  Non-Hodgkin's lymphoma
  -  Primary or metastatic solid tumor located, by radiography, in at least one of the following sites:
  -  Liver
  -  Soft tissue
  -  Pelvis
  -  Other site that is suitable for delayed contrast-enhanced MRI (e.g., peripheral lung field)
  -  Relapsed or refractory (including unresectable) disease
  -  Patients with solid tumors must have failed all curative chemotherapeutic regimens
  -  Patients with non-Hodgkin's lymphoma must be refractory to at least 2 standard chemotherapeutic regimens and rituximab
  -  Not amenable to available conventional therapies AND no standard therapy exists
  -  Measurable disease
  -  No prior or concurrent CNS metastases (brain or leptomeningeal)
  -  No primary intracranial tumor by MRI or CT scan
  -  No histologically confirmed squamous cell carcinoma of the lung
  PATIENT CHARACTERISTICS:
  Age
  -  18 and over
  Performance status
  -  ECOG 0-2
  Life expectancy
  -  Not specified
  Hematopoietic
  -  WBC ≥ 3,500/mm^3
  -  Absolute neutrophil count ≥ 1,500/mm^3
  -  Hemoglobin ≥ 9.0 g/dL
  -  Platelet count ≥ 100,000/mm^3
  -  No severe or uncontrolled hematologic condition
  Hepatic
  -  Bilirubin ≤1.5 times upper limit of normal (ULN)
  -  AST and ALT ≤ 2.5 times ULN
  -  PT and PTT normal
  -  INR normal
  -  Hepatitis B surface antigen negative
  -  Hepatitis C antibody negative
  Renal
  -  Creatinine ≤ ULN
  -  Urine protein/creatinine ratio ≤ 1
  -  No severe or uncontrolled renal condition
  Cardiovascular
  -  No clinically significant acute electrocardiographic abnormalities
  -  LVEF normal by echocardiogram or MUGA within the past 12 months if there was prior exposure to anthracyclines
  -  No untreated or uncontrolled hypertension
  -  No blood pressure > 150/100 mm Hg (despite treatment)
  -  No isolated systolic hypertension (i.e., systolic blood pressure > 180 mm Hg on at least 2 determinations [on separate days] within the past 3 months)
  -  No New York Heart Association class II - IV heart disease
  -  No active coronary artery disease requiring acute medical management
  -  No angina requiring acute medical management
  -  No congestive heart failure requiring acute medical management
  -  No ventricular arrhythmia requiring acute medical management
  -  No stroke or transient ischemic event within the past 6 months
  -  No prior or concurrent peripheral vascular disease
  -  No angiographically or ultrasonographically documented arterial or venous occlusive event
  -  No symptomatic claudication
  -  No symptomatic orthostatic hypotension
  -  No other severe or uncontrolled cardiovascular condition
  Pulmonary
  -  No severe or uncontrolled pulmonary condition
  -  No pulmonary embolism within the past 6 months
  Immunologic
  -  HIV negative
  -  No severe or uncontrolled immunologic condition
  -  No active current infection requiring antibiotics
  -  No prior hypersensitivity reaction to any recombinant proteins, including VEGF Trap
  Other
  -  No severe or uncontrolled gastrointestinal or musculoskeletal condition
  -  No psychiatric condition or adverse social circumstance that would preclude study participation
  -  No other condition that would preclude study participation
  -  Not pregnant or nursing
  -  Negative pregnancy test
  -  Fertile patients must use effective double-barrier contraception during and for 3 months after study treatment
  PRIOR CONCURRENT THERAPY:
  Biologic therapy
  -  See Disease Characteristics
  -  No prior participation in a VEGF Trap, interleukin-1 Trap, or interleukin-4/13 Trap clinical trial
  -  At least 3 weeks since prior immunotherapy and recovered
  -  No concurrent epoetin alfa, filgrastim (G-CSF), or sargramostim (GM-CSF)
  Chemotherapy
  -  See Disease Characteristics
  -  At least 3 weeks since prior chemotherapy and recovered
  Endocrine therapy
  -  No concurrent adrenal corticosteroids except low-dose replacement therapy
  -  No concurrent systemic hormonal contraceptive agents
  Radiotherapy
  -  At least 3 weeks since prior radiotherapy and recovered
  Surgery
  -  At least 3 weeks since prior major or laparoscopic surgery and recovered
  -  More than 6 months since prior surgical procedure for correction or prophylaxis of peripheral vascular insufficiency or cerebral ischemic events
  Other
  -  More than 30 days since prior investigational drugs
  -  No concurrent anticoagulant or antiplatelet drugs (e.g., warfarin, heparin, or aspirin) other than low-dose (1 mg) warfarin for maintaining patency of venous access devices
  -  No concurrent non-steroidal anti-inflammatory drugs, including cyclo-oxygenase-2 (COX-2) inhibitors
  -  No other concurrent anticancer investigational agents
  -  No other concurrent anticancer therapy

Relevance to patient case: not relevant