OBJECTIVES:

Primary

• Determine the dose-limiting toxicity, maximum feasible dose, and recommended phase II dose of cilengitide (EMD 121974) in patients with advanced solid tumors or lymphoma.
• Determine the safety and tolerability of this drug in these patients.

Secondary

• Determine the pharmacokinetics of this drug in these patients.
• Determine the antineoplastic activity of this drug in these patients.

OUTLINE: This is a dose-escalation study.

Patients receive cilengitide (EMD 121974) IV continuously on weeks 1-4. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of EMD 121974 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

PROJECTED ACCRUAL: Approximately 45 patients will be accrued for this study within 5.3-13 months.

DISEASE CHARACTERISTICS:

• Histologically confirmed solid tumor or lymphoma
• Refractory to standard therapy or no standard therapy exists
• Measurable or evaluable disease

• No active brain metastases

  • Previously treated brain metastases allowed provided the patient is not currently receiving corticosteroids
  • Primary brain neoplasms allowed, regardless of corticosteroid use

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Karnofsky 70-100%

Life expectancy

• Not specified

Hematopoietic

• WBC ≥ 3,000/mm^3
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• No life-threatening bleeding diathesis within the past 6 months

Hepatic

• Bilirubin normal (unless due to Gilbert's syndrome)

Renal

• Not specified

Cardiovascular

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

Gastrointestinal

• No prior proven gastric or duodenal ulcer
• No clinically significant gastrointestinal blood loss within the past 6 weeks

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No prior CNS hemorrhage
• No psychiatric illness or social situation that would preclude study compliance
• No other concurrent uncontrolled illness
• No ongoing or active infection

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior cilengitide (EMD 121974)
• No other concurrent biologic therapy

Chemotherapy

• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
• No concurrent chemotherapy

Endocrine therapy

• See Disease Characteristics

Radiotherapy

• More than 4 weeks since prior radiotherapy and recovered
• No concurrent palliative radiotherapy

Surgery

• Not specified

Other

• No other concurrent anticancer agents or therapies intended to treat the malignancy
• No other concurrent investigational agents

• No concurrent anticoagulation therapy that increases INR or aPTT above the normal range

  • Line prophylaxis allowed