Cilengitide (EMD 121974) in Treating Patients With Advanced Solid Tumors or Lymphoma

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Completed

CT.gov ID

NCT00077155

Collaborator

(none)

Enrollment

Location

Arm

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
AIDS-related Peripheral/Systemic Lymphoma AIDS-related Primary CNS Lymphoma Anaplastic Large Cell Lymphoma Angioimmunoblastic T-cell Lymphoma Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue Intraocular Lymphoma Nodal Marginal Zone B-cell Lymphoma Recurrent Adult Burkitt Lymphoma Recurrent Adult Diffuse Large Cell Lymphoma Recurrent Adult Diffuse Mixed Cell Lymphoma Recurrent Adult Diffuse Small Cleaved Cell Lymphoma Recurrent Adult Hodgkin Lymphoma Recurrent Adult Immunoblastic Large Cell Lymphoma Recurrent Adult Lymphoblastic Lymphoma Recurrent Adult T-cell Leukemia/Lymphoma Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma Recurrent Grade 1 Follicular Lymphoma Recurrent Grade 2 Follicular Lymphoma Recurrent Grade 3 Follicular Lymphoma Recurrent Mantle Cell Lymphoma Recurrent Marginal Zone Lymphoma Recurrent Mycosis Fungoides/Sezary Syndrome Recurrent Small Lymphocytic Lymphoma Splenic Marginal Zone Lymphoma Stage III Adult Burkitt Lymphoma Stage III Adult Diffuse Large Cell Lymphoma Stage III Adult Diffuse Mixed Cell Lymphoma Stage III Adult Diffuse Small Cleaved Cell Lymphoma Stage III Adult Hodgkin Lymphoma Stage III Adult Immunoblastic Large Cell Lymphoma Stage III Adult Lymphoblastic Lymphoma Stage III Cutaneous T-cell Non-Hodgkin Lymphoma Stage III Grade 1 Follicular Lymphoma Stage III Grade 2 Follicular Lymphoma Stage III Grade 3 Follicular Lymphoma Stage III Mantle Cell Lymphoma Stage III Marginal Zone Lymphoma Stage III Mycosis Fungoides/Sezary Syndrome Stage III Small Lymphocytic Lymphoma Stage IV Adult Burkitt Lymphoma Stage IV Adult Diffuse Large Cell Lymphoma Stage IV Adult Diffuse Mixed Cell Lymphoma Stage IV Adult Diffuse Small Cleaved Cell Lymphoma Stage IV Adult Hodgkin Lymphoma Stage IV Adult Immunoblastic Large Cell Lymphoma Stage IV Adult Lymphoblastic Lymphoma Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma Stage IV Grade 1 Follicular Lymphoma Stage IV Grade 2 Follicular Lymphoma Stage IV Grade 3 Follicular Lymphoma Stage IV Mantle Cell Lymphoma Stage IV Marginal Zone Lymphoma Stage IV Mycosis Fungoides/Sezary Syndrome Stage IV Small Lymphocytic Lymphoma Unspecified Adult Solid Tumor, Protocol Specific	Drug: cilengitide	Phase 1

Detailed Description

PRIMARY OBJECTIVES:

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 OBJECTIVES:

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

45 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I Study Of Continuous Infusion EMD 121974 In Patients With Solid Tumors

Study Start Date :

Dec 1, 2003

Actual Primary Completion Date :

Jun 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (cilengitide) 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 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.	Drug: cilengitide Other Names: EMD 121974

Arm

Intervention/Treatment

Experimental: Treatment (cilengitide)

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 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.

Drug: cilengitide

Other Names:

EMD 121974

Outcome Measures

Primary Outcome Measures

Maximum feasible dose defined as the highest dose studied for which the incidence of DLT is less than 33% or the highest safe dose in our study, limited to a maximum MFD dose of 40 mg/hr [4 weeks]

Secondary Outcome Measures

Pharmacokinetics of EMD 121974 [Up to 8 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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