A Phase I, Open Label Multiple Dose, Safety and Pharmacokinetic Study of Intravenously Administered Humanized Anti-VEGF Monoclonal Antibody (HuMV833) to Patients With Relapsed or Refractory Solid Tumors
18 Years
N/A
Both
Unspecified Adult Solid Tumor, Protocol Specific
Trial Information
A Phase I, Open Label Multiple Dose, Safety and Pharmacokinetic Study of Intravenously Administered Humanized Anti-VEGF Monoclonal Antibody (HuMV833) to Patients With Relapsed or Refractory Solid Tumors
OBJECTIVES: I. Determine the preliminary tolerability and safety of monoclonal antibody VEGF
(MOAB VEGF) in patients with relapsed or refractory progressive solid tumors. II. Determine
the optimum biologically active dose of MOAB VEGF for further evaluation based on
exploratory methods. III. Determine the maximum tolerated dose of MOAB VEGF in these
patients. IV. Determine a safe dose of MOAB VEGF for further clinical studies. V. Determine
the dose limiting toxicity and pharmacokinetics of this regimen in these patients. VI.
Determine the response rate in patients treated with this regimen.
OUTLINE: This is a dose escalation, multicenter study. Patients receive monoclonal antibody
VEGF (MOAB VEGF) IV over 1 hour on days 1, 15, 22, and 29. Patients with partial response
(PR), complete response (CR), or stable disease (SD) after completion of the fourth dose may
receive weekly infusions for up to 6 months in the absence of disease progression or
unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of MOAB VEGF until
the maximum tolerated dose (MTD) and optimum biologically active dose (OBAD) are determined.
The MTD is defined as the dose at which 1 of 6 patients experiences dose limiting toxicity.
The OBAD is defined as the dose at which vascular endothelial growth factor is optimally
inhibited. Patients with PR, CR, or SD are evaluated every 6 weeks until disease progression
or initiation of another treatment. Patients who discontinue treatment prematurely due to
toxicity are followed weekly until resolution of any associated toxicity. Patients who
discontinue treatment after the fourth dose of MOAB VEGF for any reason other than toxicity
are followed every month for up to 6 months.
PROJECTED ACCRUAL: A maximum of 25 patients will be accrued for this study.
Inclusion Criteria
DISEASE CHARACTERISTICS: Histologically proven relapsed or refractory progressive solid
tumor that is not amenable to treatment with standard therapies No brain involvement or
leptomeningeal disease
PATIENT CHARACTERISTICS: Age: 18 and over Menopausal status: Postmenopausal Performance
status: ECOG 0-2 Life expectancy: At least 3 months Hematopoietic: Absolute neutrophil
count at least 1,500/mm3 Platelet count at least 100,000/mm3 Hemoglobin at least 10 g/dL
No bleeding or clotting abnormalities Hepatic: Bilirubin no greater than 1.5 times upper
limit of normal (ULN) AST or ALT no greater than 2.5 times ULN Alkaline phosphatase no
greater than 2.5 times ULN Renal: Creatinine no greater than 1.4 mg/dL Cardiovascular:
Normal cardiac function by 12 lead ECG Other: No unstable systemic disease or uncontrolled
infection that would preclude study participation No concurrent infection requiring
antibiotics Not pregnant or nursing Negative pregnancy test Fertile patients must use
effective contraception during and for 70 days after study No psychologic, familial,
sociologic, or geographic condition that could preclude compliance HIV negative HTLV-1
negative Hepatitis B surface antigen negative No other prior or concurrent malignancy
except basal cell skin cancer or carcinoma in situ of the cervix No allergy to protein
therapeutics
PRIOR CONCURRENT THERAPY: Biologic therapy: At least 4 weeks since prior immunotherapy and
recovered Chemotherapy: At least 4 weeks since prior chemotherapy and recovered Endocrine
therapy: At least 4 weeks since prior hormonal antitumor therapy No concurrent steroids or
hormonal therapy Radiotherapy: At least 4 weeks since prior radiotherapy and recovered
Concurrent radiotherapy allowed Surgery: Greater than 4 weeks since prior surgery except
biopsy or fine needle aspiration of tumor masses Other: At least 4 weeks since other prior
investigational drugs or therapies No other concurrent anticancer treatments No other
concurrent investigational therapy
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Principal Investigator
Gordon Jayson, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Christie Hospital NHS Foundation Trust
Authority:
United States: Federal Government
Study ID:
EORTC-13992
NCT ID:
NCT00005061
Start Date:
December 1999
Completion Date:
Related Keywords:
- Unspecified Adult Solid Tumor, Protocol Specific
- unspecified adult solid tumor, protocol specific
- Neoplasms
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