Monoclonal Antibody Therapy in Treating Patients With Refractory Advanced Solid Tumors or Lymphoma

A Phase I Study Of Medi 522 In Patients With Advanced Tumors

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.

OBJECTIVES:

• 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 patients.
• 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 these patients.
• 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 unacceptable toxicity.

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.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed solid tumor or lymphoma that is refractory to currently available standard therapies or for which there are no curative therapies
• No known brain metastases

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• More than 12 weeks

Hematopoietic

• 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

Hepatic

• Bilirubin normal
• AST/ALT no greater than 2.5 times upper limit of normal
• INR/PTT normal

Renal

• Creatinine normal OR
• Creatinine clearance at least 60 mL/min

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 6 months after study participation
• 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:

Biologic therapy

• Not specified

Chemotherapy

• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered

Endocrine therapy

• Not specified

Radiotherapy

• More than 4 weeks since prior radiotherapy and recovered

Surgery

• More than 4 weeks since prior surgery

Other

• No other concurrent investigational agents
• No other concurrent anticancer agents or therapies (commercial or investigational)