Clinical trial NCT00082823: Intravenous VEGF Trap in Treating Patients With Relapsed or Refractory Advanced Solid Tumors or Non-Hodgkin's Lymphoma
Official title: An Open-Label, Long-Term, Safety and Tolerability Study of VEGF Trap Administered Intravenously in Patients With Advanced Solid Tumors or Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cancer
Keywords: 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
recurrent adult diffuse mixed cell lymphoma
stage IV 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
advanced adult primary liver cancer
recurrent 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
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-05-19
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Intravenous VEGF Trap may stop the growth of solid tumors or non-Hodgkin's lymphoma by stopping blood flow to the cancer.

PURPOSE: This phase I trial is studying the side effects of 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 steady-state pharmacokinetics of this drug in these patients.
* Determine the ability of this drug to bind circulating vascular endothelial growth factor in these patients.
* Determine whether antibodies to this drug develop in these patients.
* Determine, preliminarily, the ability of repeated doses of this drug to alter tumor growth and vascular permeability in these patients.

OUTLINE: This is an open-label, multicenter, extension study.

Patients receive VEGF Trap\* IV over 1 hour on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

NOTE: \*Patients receive the same drug dose that they received in MSKCC-03137 (VGFT-ST-0202)

Patients are followed monthly for 3 months.

PROJECTED ACCRUAL: A total of 25 patients will be accrued for this study within 3-6 months.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed non-Hodgkin's lymphoma OR primary or metastatic solid tumor located in at least one of the following sites:

  * Liver
  * Soft tissue
  * Pelvis
  * Other site that is suitable for delayed contrast-enhancing MRI
* Relapsed or refractory disease

  * Failed all conventional therapeutic options AND not amenable to existing therapeutic options
* Must have completed the active phase (through study visit 9) of MSKCC-03137 (VGFT-ST-0202) without experiencing dose-limiting toxicity
* No prior or concurrent CNS metastases (brain or leptomeningeal)

  * No new neurological symptoms during treatment on MSKCC-03137 (VGFT-ST-0202)

PATIENT CHARACTERISTICS:

Age

* 18 and over

Performance status

* Not specified

Life expectancy

* Not specified

Hematopoietic

* No severe or uncontrolled hematologic condition

Hepatic

* Not specified

Renal

* No severe or uncontrolled renal condition

Cardiovascular

* No severe or uncontrolled cardiovascular condition

Pulmonary

* No severe or uncontrolled pulmonary condition

Other

* No severe or uncontrolled gastrointestinal, immunologic, or musculoskeletal condition
* No other medical or psychiatric condition or adverse social circumstance 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

* No concurrent epoetin alfa, filgrastim (G-CSF), or sargramostim (GM-CSF)

Chemotherapy

* Not specified

Endocrine therapy

* No concurrent adrenal corticosteroids, except low-dose replacement therapy
* No concurrent systemic hormonal contraceptive agents

Radiotherapy

* Not specified

Surgery

* Not specified

Other

* No concurrent non-steroidal anti-inflammatory drugs, including cyclo-oxygenase-2 (COX-2) inhibitors
* No concurrent anticoagulant or antiplatelet drugs, including warfarin, heparin, or aspirin

  * Concurrent low-dose (i.e., 1 mg) warfarin for maintaining patency of venous access devices allowed
* No other concurrent standard or investigational agents for this malignancy

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan - Kettering Cancer Center
state: New York
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: William P. Tew, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lockhart AC, Rothenberg ML, Dupont J, Cooper W, Chevalier P, Sternas L, Buzenet G, Koehler E, Sosman JA, Schwartz LH, Gultekin DH, Koutcher JA, Donnelly EF, Andal R, Dancy I, Spriggs DR, Tew WP. Phase I study of intravenous vascular endothelial growth factor trap, aflibercept, in patients with advanced solid tumors. J Clin Oncol. 2010 Jan 10;28(2):207-14. doi: 10.1200/JCO.2009.22.9237. Epub 2009 Nov 30.
citation: Wang-Gillam A, Tew WP, Rothenberg ML, Dupont J, Cooper W, Sternas L, Buzenet G, Sosman JA, Spriggs DR, Lockhart AC. A phase I study of subcutaneously administered aflibercept (VEGF trap) in a new formulation in patients with advanced solid tumors. Invest New Drugs. 2012 Oct;30(5):1958-61. doi: 10.1007/s10637-011-9753-y. Epub 2011 Oct 15.