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An Open Label, Sequential Cohort Dose-Escalation Safety, Tolerability and Pharmacokinetic Study of VEGF Trap Administered Intravenously in Patients With Advanced Solid Tumors or Lymphoma


Phase 1
18 Years
N/A
Not Enrolling
Both
Cancer

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Trial Information

An Open Label, Sequential Cohort Dose-Escalation Safety, Tolerability and Pharmacokinetic Study of VEGF Trap Administered Intravenously in Patients With Advanced Solid Tumors or Lymphoma


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.

Inclusion Criteria


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

Type of Study:

Interventional

Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Principal Investigator

William P. Tew, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center

Authority:

United States: Federal Government

Study ID:

REGENERON-VGFT-ST-0202

NCT ID:

NCT00083213

Start Date:

January 2004

Completion Date:

Related Keywords:

  • Cancer
  • recurrent grade 1 follicular lymphoma
  • stage IV grade 1 follicular lymphoma
  • recurrent grade 2 follicular lymphoma
  • stage IV grade 2 follicular lymphoma
  • recurrent grade 3 follicular lymphoma
  • stage IV grade 3 follicular lymphoma
  • recurrent adult diffuse small cleaved cell lymphoma
  • stage IV adult diffuse small cleaved cell lymphoma
  • recurrent adult diffuse large cell lymphoma
  • stage IV adult diffuse large cell lymphoma
  • stage IV adult diffuse mixed cell lymphoma
  • recurrent adult diffuse mixed cell lymphoma
  • recurrent adult immunoblastic large cell lymphoma
  • stage IV adult immunoblastic large cell lymphoma
  • recurrent adult Burkitt lymphoma
  • stage IV adult Burkitt lymphoma
  • recurrent mantle cell lymphoma
  • stage IV mantle cell lymphoma
  • recurrent adult lymphoblastic lymphoma
  • stage IV adult lymphoblastic lymphoma
  • unspecified adult solid tumor, protocol specific
  • recurrent adult soft tissue sarcoma
  • recurrent adult primary liver cancer
  • advanced adult primary liver cancer
  • recurrent cervical cancer
  • stage IVA cervical cancer
  • stage IVB cervical cancer
  • fallopian tube cancer
  • ovarian sarcoma
  • recurrent ovarian epithelial cancer
  • stage IV ovarian epithelial cancer
  • recurrent endometrial carcinoma
  • stage IV endometrial carcinoma
  • recurrent uterine sarcoma
  • stage IV uterine sarcoma
  • recurrent ovarian germ cell tumor
  • stage IV ovarian germ cell tumor
  • ovarian stromal cancer
  • recurrent vaginal cancer
  • stage IVA vaginal cancer
  • stage IVB vaginal cancer
  • recurrent prostate cancer
  • stage IV prostate cancer
  • recurrent penile cancer
  • stage IV penile cancer
  • recurrent malignant testicular germ cell tumor
  • stage III malignant testicular germ cell tumor
  • recurrent bladder cancer
  • stage IV bladder cancer
  • recurrent vulvar cancer
  • stage IVB vulvar cancer
  • distal urethral cancer
  • proximal urethral cancer
  • recurrent urethral cancer
  • urethral cancer associated with invasive bladder cancer
  • primary peritoneal cavity cancer
  • recurrent marginal zone lymphoma
  • recurrent small lymphocytic lymphoma
  • stage IV small lymphocytic lymphoma
  • stage IV marginal zone lymphoma
  • extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
  • nodal marginal zone B-cell lymphoma
  • splenic marginal zone lymphoma
  • stage IV adult soft tissue sarcoma
  • Lymphoma
  • Lymphoma, Non-Hodgkin
  • Lymphoma, Large-Cell, Immunoblastic

Name

Location

Memorial Sloan - Kettering Cancer CenterNew York, New York  10021