EMD 121974 in Treating Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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Phase I trial to study the effectiveness of EMD 121974 in treating patients who have advanced solid tumors. EMD 121974 may slow the growth of solid tumors by stopping blood flow to the tumor

Detailed Description
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OBJECTIVES: I. Determine the toxic effects and maximum tolerated dose of EMD 121974 in patients with advanced solid tumors. II. Determine the biologic activity of this drug in these patients. III. Determine the pharmacokinetic profile and plasma biological effects of this drug and identify any relationship with its biologic activity or observed toxicity in these patients. IV. Determine, preliminarily, the antitumor efficacy of this drug in these patients. OUTLINE: This is a dose-escalation study. Patients receive EMD 121974 IV over 1 hour twice weekly. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-10 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 6 patients experience dose-limiting toxicity.

Official Title
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A Phase I Study of EMD 121974 in Patients With Advanced Solid Tumors

Conditions
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Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Drug: cilengitide
* Other: pharmacological study
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed solid tumor that is refractory to standard therapy or for which no standard therapy exists Tumors must be amenable to minimally-invasive biopsy (i.e., tumors must be superficial enough to be sampled by punch biopsy or core biopsy procedure without radiologic guidance)* No uncontrolled brain metastases, including symptomatic lesions or lesions requiring glucocorticoids and/or anticonvulsants to suppress symptoms Negative brain scan required if there are signs and symptoms suggestive of brain metastasis Performance status - ECOG 0-2 Performance status - Karnofsky 60-100% At least 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 Hemoglobin at least 9 g/dL Bilirubin normal AST and ALT no greater than 2.5 times upper limit of normal Creatinine normal Creatinine clearance at least 60 mL/min No symptomatic congestive heart failure No unstable angina pectoris No ongoing or active infection No other concurrent serious systemic disorders (e.g., significant CNS illness) that would preclude study No concurrent psychiatric illness or social situations that would preclude study Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No other concurrent anticancer immunotherapy Concurrent hematologic growth factors for cytopenias allowed At least 4 weeks since prior anticancer chemotherapy (6 weeks for nitrosoureas, carmustine, or mitomycin) and recovered See Disease Characteristics No concurrent anticancer hormonal therapy Concurrent oral contraceptives or postmenopausal hormone replacement allowed Recovered from prior radiotherapy At least 2 weeks since prior palliative radiotherapy to bone or brain metastases At least 4 weeks since prior anticancer radiotherapy No concurrent anticancer radiotherapy Not specified At least 4 weeks since prior anticancer therapy and recovered At least 4 weeks since prior investigational agents Any number of prior therapies allowed No other concurrent anticancer investigational or commercial agents No concurrent combination antiretroviral therapy for HIV-positive patients

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (cilengitide)<br>Patients receive EMD 121974 IV over 1 hour twice weekly. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. | Drug: cilengitide<br>* Given IV<br>* Other names: EMD 121974;Other: pharmacological study<br>* Correlative studies<br>* Other names: pharmacological studies;Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MTD of cilengitide defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. | Graded according to the NCI Common Toxicity Criteria version 2.0. | 4 weeks | 
| Toxic effects of cilengitide described as an adverse event that has an attribution of possibly, probably or definitely related to investigational treatment | Graded according to the NCI Common Toxicity Criteria version 2.0. | Up to 4 years | 
| Biological activity of this regimen | Measured buy TUNEL assay, CD31 immunohistochemistry, dynamic contrast-enhanced MRI, and FDG-PET scan. | Up to 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of cilengitide |  | At 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 8.0, and 24.0 hours post-end-of-infusion on day 1 of course 1 | 
| Observation of response consisting of complete response, partial response, or stable disease, evaluated using the RECIST criteria |  | Up to 4 years | 
| Time to progression |  | Up to 4 years |