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

NCT00093964 | Completed Phase 2 Results

• 1 other identifier: EMD 121974-009
• Study Type: interventional
• Target: 81
• Locations: 1 country
• Sites: 17

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

Keywords

Brain cancer; Brain tumor

Outcome Measures

Primary Outcomes (1)

• Percentage of Subjects With Progression-free Survival

  Progression-free survival was defined as subjects who survived greater than or equal to (\>=) 180 days without disease progression. Disease progression was assessed as per independent central blinded radiology assessment.

  Month 6

Secondary Outcomes (14)

• Percentage of Subjects With Overall Response Rate

  From the start of treatment up to 6 years

• Time to Disease Progression

  From the start of treatment until disease progression (assessed up to a maximum of 6 years)

• Overall Survival Time

  From the start of treatment until death (assessed up to a maximum of 6 years)

• Percentage of Subjects With 1-year of Survival Rate

  From the start of treatment up to 1 year

• Maximum Observed Plasma Concentration (Cmax)

  Pre-dose, 1, 1.5, 2, 3, 4, 8, 24 hours post-infusion on Day 1 of Week 1 in Cycle 1 and 2

Study Arms (2)

Cilengitide 500 Milligram (mg)

EXPERIMENTAL

Drug: Cilengitide 500 mg

Cilengitide 2000 mg

EXPERIMENTAL

Drug: Cilengitide 2000 mg

Interventions

Cilengitide 500 mg 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.

Also known as: EMD 121974

Cilengitide 500 Milligram (mg)

Cilengitide 2000 mg 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.

Also known as: EMD 121974

Cilengitide 2000 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• EMD Serono: lead

Study Sites (17)

University of Alabama at Birmingham

Birmingham, Alabama, 35294-3280, United States

Location

Barrow Neurological Institute

Phoenix, Arizona, 85013, United States

Location

UCLA Medical Center

Los Angeles, California, 90095, United States

Location

Denise Damek

Aurora, Colorado, 80010, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Indiana University Medical Center

Indianapolis, Indiana, 46202, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

University of Massachusetts

Worcester, Massachusetts, 01655, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10021, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Good Samaritan Hospital/Tri Health Hatton Center

Cincinnati, Ohio, 45206, United States

Location

Baylor University Medical Center at Dallas

Dallas, Texas, 75246, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Vermont/Fletcher Allen Healthcare

Burlington, Vermont, 05401, United States

Location

University of Virginia Health System

Charlottesville, Virginia, 22903, United States

Location

Related Publications (1)

• 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.

  PMID: 18981465 RESULT

MeSH Terms

Conditions

Glioblastoma; Brain Neoplasms

Interventions

Cilengitide

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Results Point of Contact

• Title: Merck KGaA Communication Center
• Organization: Merck Healthcare, a business of Merck KGaA, Darmstadt, Germany

service@merckgroup.com

+49-6151-72-5200

Study Officials

• Medical Responsible

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

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 7, 2004
• First Posted: October 11, 2004
• Study Start: October 13, 2004
• Primary Completion: October 28, 2005
• Study Completion: October 21, 2010
• Last Updated: April 16, 2019
• Results First Posted: April 16, 2019

Record last verified: 2019-01

Locations

US (17)