RATIONALE: Monoclonal antibodies can locate cancer cells and either kill them or deliver
cancer-killing substances to them without harming normal cells.
PURPOSE: Phase I trial to study the effectiveness of monoclonal antibody therapy in treating
patients who have refractory advanced solid tumors or lymphoma.
- Determine the maximum tolerated dose (MTD) of monoclonal antibody anti-alpha V beta 3
integrin (MEDI 522) in patients with refractory advanced solid tumors or lymphoma.
- Determine the safety and tolerability of this drug in these patients.
- Demonstrate significant binding of this drug to its molecular target in vivo in these
- Determine the effects of this drug on angiogenesis in these patients.
- Determine antitumor activity of this drug by measuring tumor size and glucose uptake in
- Determine the pharmacokinetics of this drug in these patients.
- Determine a recommended phase II dose of this drug based on either the MTD or the
optimal biologic response in these patients.
OUTLINE: This is a dose-escalation study.
Patients receive monoclonal antibody anti-alpha V beta 3 integrin (Medi 522) IV over 30
minutes weekly. Courses repeat every 4 weeks in the absence of disease progression or
Cohorts of 6 patients receive escalating doses of Medi 522 until the maximum tolerated dose
(MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 6
patients experience dose-limiting toxicity.
PROJECTED ACCRUAL: Approximately 6-30 patients will be accrued for this study.
- Histologically or cytologically confirmed solid tumor or lymphoma that is refractory
to currently available standard therapies or for which there are no curative
- No known brain metastases
- 18 and over
- ECOG 0-2
- More than 12 weeks
- WBC at least 3,000/mm^3
- Absolute neutrophil count at least 1,500/mm^3
- Platelet count at least 100,000/mm^3
- No prior bleeding disorder
- Bilirubin normal
- AST/ALT no greater than 2.5 times upper limit of normal
- INR/PTT normal
- Creatinine normal OR
- Creatinine clearance at least 60 mL/min
- No symptomatic congestive heart failure
- No unstable angina pectoris
- No cardiac arrhythmia
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 6 months after study
- HIV negative
- T4 or thyroid stimulating hormone normal
- No thyroid disease
- No prior allergic reactions attributed to compounds of similar chemical or biologic
composition to study drug (e.g., rituximab or immunoglobulin G)
- No ongoing or active infection
- No other uncontrolled concurrent illness that would preclude study participation
- No psychiatric illness or social situation that would preclude study participation
PRIOR CONCURRENT THERAPY:
- Not specified
- More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
- Not specified
- More than 4 weeks since prior radiotherapy and recovered
- More than 4 weeks since prior surgery
- No other concurrent investigational agents
- No other concurrent anticancer agents or therapies (commercial or investigational)
Douglas McNeel, MD, PhD
University of Wisconsin, Madison