Cilengitide (EMD 121974) for Recurrent Glioblastoma Multiforme (Brain Tumor)

NCT ID: NCT00093964

Last Updated: 2019-04-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 81 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-10-13
• Study Completion Date: 2010-10-21

Brief Summary

This study will investigate clinical activity, safety, and tolerability of the anti-angiogenic compound cilengitide (EMD 121974) in the treatment of first recurrence of glioblastoma multiforme (GBM).

Conditions

Glioblastoma Multiforme

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cilengitide 500 Milligram (mg)

Group Type: EXPERIMENTAL

Cilengitide 500 mg

Intervention Type: DRUG

Subjects will receive 1-hour intravenous infusion of 500 mg cilengitide twice weekly on Day 1 and 4 of each week during every 4-week cycle, for a total of 8 infusions per cycle. Cycles were repeated without pause until progressive disease (PD), unacceptable adverse events (AEs), or withdrawal of consent.

Cilengitide 2000 mg

Group Type: EXPERIMENTAL

Cilengitide 2000 mg

Intervention Type: DRUG

Subjects will receive 1-hour intravenous infusion of 2000 mg cilengitide twice weekly on Day 1 and 4 of each week during every 4-week cycle, for a total of 8 infusions per cycle. Cycles were repeated without pause until progressive disease (PD), unacceptable adverse events (AEs), or withdrawal of consent.

Interventions

Cilengitide 500 mg

Subjects will receive 1-hour intravenous infusion of 500 mg cilengitide twice weekly on Day 1 and 4 of each week during every 4-week cycle, for a total of 8 infusions per cycle. Cycles were repeated without pause until progressive disease (PD), unacceptable adverse events (AEs), or withdrawal of consent.

Intervention Type: DRUG

Cilengitide 2000 mg

Subjects will receive 1-hour intravenous infusion of 2000 mg cilengitide twice weekly on Day 1 and 4 of each week during every 4-week cycle, for a total of 8 infusions per cycle. Cycles were repeated without pause until progressive disease (PD), unacceptable adverse events (AEs), or withdrawal of consent.

Intervention Type: DRUG

Other Intervention Names

EMD 121974; EMD 121974

Eligibility Criteria

Inclusion Criteria

• Written informed consent obtained before undergoing any study-related activities.
• Males or females 18 years of age or older who can be treated in an outpatient setting.
• Histologically proven GBM, which is recurrent or progressive following surgery or biopsy, external beam radiation therapy, and 1 previous regimen of systemic chemotherapy (Gliadel wafer therapy is not considered systemic chemotherapy). Malignancy is to be documented with a previous histopathological report.
• GBM recurring only in the contralateral hemisphere must be histologically confirmed by biopsy. GBM recurring bilaterally does not need to be histologically confirmed by biopsy (i.e., if recurrence is ipsilateral and contralateral).
• Archived tumor tissue specimens from the GBM surgery or biopsy must be available for central pathology review and exploratory analysis of angiogenic markers (e.g. αvβ3 and αvβ5 integrins).
• Measurable disease (solid contrast-enhancing lesion greater than or equal to (>=)1 cm in any dimension) evaluated by gadolinium-enhanced magnetic resonance imaging (Gd MRI) within 2 weeks prior to the first dose of EMD 121974.
• At least 12 weeks have elapsed since the last radiation treatment, and at least 4 weeks have elapsed since the last chemotherapy dose (at least 6 weeks for nitrosourea-containing chemotherapy) prior to the first dose of EMD 121974.
• If the subject underwent recent surgery, status must be >=2 weeks post surgery or >=1 week post biopsy, in stable condition, and maintained on a stable corticosteroid regimen for >=5 days prior to first dose of EMD 121974.
• Karnofsky Performance Score (KPS) of >=70%.
• Subjects with the potential for pregnancy or impregnating their partner must agree to follow acceptable methods of birth control to avoid conception during the study and for at least 6 months after receiving the last dose of study drug.
• Women of childbearing potential must have a negative pregnancy test at screening.
• Laboratory values (within 1 week prior to the first dose of EMD 121974, except for blood count and Prothrombin time (PT)/Partial thromboplastin time (PTT), which are to be within 72 hours of the first dose): Absolute neutrophil count >=1500/millimeter (mm)^3. Platelets >=100,000/mm^3. Creatinine less than or equal to (<=) 1.5 milligram/deciliter (mg/dL) or creatinine clearance >=60 mL/min. Hematocrit >=30%. Prothrombin time (PT) and partial thromboplastin time (PTT) within normal limits. Hemoglobin >=10 mg/dL. Total bilirubin <=1.5 times the upper limit of normal. Aspartate aminotransferase and alanine aminotransferase <=2.5 times above upper limit of normal.
• No more than 8 weeks have elapsed since recurrence was detected

Exclusion Criteria

• Prior radiation therapy greater than (>) 66 Gray.
• Subject anticipates undergoing elective surgery, dental extraction, or invasive dental procedures.
• History of recent peptic ulcer disease (endoscopically proven gastric ulcer, duodenal ulcer, or esophageal ulcer) within 6 months of enrollment.
• History of prior malignancy. Subjects with curatively treated cervical carcinoma in situ or basal cell carcinoma of the skin, or subjects who have been free of other malignancies for ≥5 years are eligible for this study.
• History of coagulation disorder associated with bleeding or recurrent thrombotic events.
• Concurrent illness, including severe infection, which may jeopardize the ability of the subject to receive the procedures outlined in this protocol with reasonable safety.
• Subject is pregnant, anticipates becoming pregnant within 6 months after study participation, or is currently breast-feeding.
• Receiving concurrent investigational agents or has received an investigational agent within the past 30 days prior to the first dose of EMD 121974.
• Prior antiangiogenic therapy.
• Placement of Gliadel wafer at surgery for recurrence.
• Unable to undergo Gd MRI.
• Current known alcohol dependence or drug abuse.
• Requiring concomitant chemotherapy.
• Treatment with a prohibited concomitant medication.
• Known hypersensitivity to the study treatment.
• Legal incapacity or limited legal capacity.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

EMD Serono

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Responsible

Role: STUDY_DIRECTOR

EMD Serono Inc., a business of Merck KGaA, Darmstadt, Germany

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

Barrow Neurological Institute

Phoenix, Arizona, United States

UCLA Medical Center

Los Angeles, California, United States

Denise Damek

Aurora, Colorado, United States

Northwestern University

Chicago, Illinois, United States

Indiana University Medical Center

Indianapolis, Indiana, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

University of Massachusetts

Worcester, Massachusetts, United States

Henry Ford Health System

Detroit, Michigan, United States

Washington University

St Louis, Missouri, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Duke University Medical Center

Durham, North Carolina, United States

Good Samaritan Hospital/Tri Health Hatton Center

Cincinnati, Ohio, United States

Baylor University Medical Center at Dallas

Dallas, Texas, United States

University of Texas MD Anderson Cancer Center

Houston, Texas, United States

University of Vermont/Fletcher Allen Healthcare

Burlington, Vermont, United States

University of Virginia Health System

Charlottesville, Virginia, United States

Countries

United States

References

Reardon DA, Fink KL, Mikkelsen T, Cloughesy TF, O'Neill A, Plotkin S, Glantz M, Ravin P, Raizer JJ, Rich KM, Schiff D, Shapiro WR, Burdette-Radoux S, Dropcho EJ, Wittemer SM, Nippgen J, Picard M, Nabors LB. Randomized phase II study of cilengitide, an integrin-targeting arginine-glycine-aspartic acid peptide, in recurrent glioblastoma multiforme. J Clin Oncol. 2008 Dec 1;26(34):5610-7. doi: 10.1200/JCO.2008.16.7510. Epub 2008 Nov 3.

Reference Type: RESULT

PMID: 18981465 (View on PubMed)

Other Identifiers

EMD 121974-009

Identifier Type: -

Identifier Source: org_study_id

NCT00103064

Identifier Type: -

Identifier Source: nct_alias

NCT00119288

Identifier Type: -

Identifier Source: nct_alias