EMD 121974 in Treating Patients With Advanced Solid Tumors

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

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

Study Overview

• Status: Completed
• Conditions: Unspecified Adult Solid Tumor, Protocol Specific
• Intervention / Treatment: Other: laboratory biomarker analysis; Other: pharmacological study; Drug: cilengitide

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Denver, Colorado, United States, 80217-3364
      • University of Colorado

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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	Time Frame
Time to progression	Up to 4 years
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

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Michele Basche, University of Colorado, Denver

Study record dates

Study Major Dates

• Study Start: May 1, 2001
• Primary Completion (Actual): May 1, 2005

Study Registration Dates

• First Submitted: August 10, 2001
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): January 25, 2013
• Last Update Submitted That Met QC Criteria: January 24, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: NCI-2012-02392; U01CA099176 (U.S. NIH Grant/Contract); 00-1096; CDR0000068786 (Registry Identifier: PDQ (Physician Data Query))