A Phase I Study Of Continuous Infusion EMD 121974 In Patients With Solid Tumors
A Phase I Study Of Continuous Infusion EMD 121974 In Patients With Solid Tumors
This phase I trial is studying the side effects and best dose of EMD 121974 in treating patients with solid tumors or lymphoma. Cilengitide (EMD 121974) may stop the growth of cancer cells by stopping blood flow to the cancer
PRIMARY OBJECTIVES:
I. 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.
II. Determine the safety and tolerability of this drug in these patients.
SECONDARY OBJECTIVES:
I. Determine the pharmacokinetics of this drug in these patients. II. 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.
Inclusion Criteria:
Histologically confirmed solid tumor or lymphoma
Refractory to standard therapy or no standard therapy exists
Measurable or evaluable disease
No active brain metastases
Performance status - Karnofsky 70-100%
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
Bilirubin normal (unless due to Gilbert's syndrome)
No symptomatic congestive heart failure
No unstable angina pectoris
No cardiac arrhythmia
No prior proven gastric or duodenal ulcer
No clinically significant gastrointestinal blood loss within the past 6 weeks
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
No prior cilengitide (EMD 121974)
No other concurrent biologic therapy
More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
No concurrent chemotherapy
See Disease Characteristics
More than 4 weeks since prior radiotherapy and recovered
No concurrent palliative radiotherapy
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