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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
EMD Serono
ClinicalTrials.gov Identifier:
NCT00093964
First received: October 7, 2004
Last updated: March 17, 2014
Last verified: March 2014
  Purpose

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).


Condition Intervention Phase
Glioblastoma Multiforme
Drug: EMD 121974
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multicenter, Open-label, Randomized, Uncontrolled, Phase IIa Trial in Subjects With Recurrent Glioblastoma Multiforme to Investigate the Clinical Activity, Safety, and Tolerability of Cilengitide (EMD 121,974) Administered as a Single Agent.

Resource links provided by NLM:


Further study details as provided by EMD Serono:

Primary Outcome Measures:
  • Rate of 6-month Progression Free Survival [ Time Frame: undefined ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Response rate [ Time Frame: undefined ] [ Designated as safety issue: No ]
  • Time to disease progression [ Time Frame: undefined ] [ Designated as safety issue: No ]
  • survival time, safety, tolerability and PK [ Time Frame: undefined ] [ Designated as safety issue: Yes ]
  • Rate of 1-year survival [ Time Frame: undefined ] [ Designated as safety issue: No ]

Enrollment: 81
Study Start Date: October 2004
Study Completion Date: December 2007
Primary Completion Date: April 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: EMD 121974

500 mg EMD 121974 IV (in the vein) twice weekly on Days 1 and 4 during a 4-week cycle for a total of 8 infusions per cycle.

Cycles will be repeated without pause until disease progression or unacceptable toxicity develops

Experimental: 2 Drug: EMD 121974

2000 mg EMD 121974 IV (in the vein) twice weekly on Days 1 and 4 during a 4-week cycle for a total of 8 infusions per cycle.

Cycles will be repeated without pause until disease progression or unacceptable toxicity develops.


Detailed Description:

Angiogenesis (growth of new blood vessels) is important for tumor growth. Cilengitide (EMD 121974) inhibits two receptor proteins (proteins on cell surface), called integrins αvβ3 and αvβ5, which appear to be important in the process of angiogenesis. Cilengitide has been shown to inhibit angiogenesis and growth of several different experimental tumors in animals. Some tumors themselves express integrin αvβ3 and use it as a survival factor (e.g. glioblastoma multiforme), so cilengitide might target both endothelial cells (cells of blood vessels) and the tumor itself triggering tumor cell apoptosis (programmed cell death).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  • Subjects initially diagnosed with other conditions similar to GBM (such as anaplastic astrocytoma [AA] or low grade glioma) that subsequently progressed to histologically proven GBM and have had surgery or biopsy, external beam radiation therapy, and 1 previous regimen of systemic chemotherapy for the original diagnosis are eligible if they meet all inclusion criteria.
  • 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. avb3 and avb5 integrins).
  • Measurable disease (solid contrast-enhancing lesion ~1 cm in any dimension) evaluated by 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 PT/PTT, which are to be within 72 hours of the first dose): * Absolute neutrophil count ≥1500/mm 3. * Platelets ≥ 100,000/mm 3. * Creatinine ≤ 1.5 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 >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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00093964

Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294-3280
United States, Arizona
Barrow Neurological Institute
Phoenix, Arizona, United States, 85013
United States, California
UCLA Medical Center
Los Angeles, California, United States, 90095
United States, Colorado
Denise Damek
Aurora, Colorado, United States, 80010
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611
United States, Indiana
Indiana University Medical Center
Indianapolis, Indiana, United States, 46202
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
University of Massachusetts
Worcester, Massachusetts, United States, 01655
United States, Michigan
Henry Ford Health System
Detroit, Michigan, United States, 48202
United States, Missouri
Washington University
St. Louis, Missouri, United States, 63110
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10021
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Ohio
Good Samaritan Hospital/Tri Health Hatton Center
Cincinnati, Ohio, United States, 45206
United States, Texas
Baylor University Medical Center at Dallas
Dallas, Texas, United States, 75246
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Vermont
University of Vermont/Fletcher Allen Healthcare
Burlington, Vermont, United States, 05401
United States, Virginia
University of Virginia Health System
Charlottesville, Virginia, United States, 22903
Sponsors and Collaborators
EMD Serono
Investigators
Principal Investigator: David Reardon, MD Duke University
  More Information

No publications provided

Responsible Party: EMD Serono
ClinicalTrials.gov Identifier: NCT00093964     History of Changes
Obsolete Identifiers: NCT00103064, NCT00119288
Other Study ID Numbers: EMD 121974-009
Study First Received: October 7, 2004
Last Updated: March 17, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by EMD Serono:
brain cancer
brain tumor

Additional relevant MeSH terms:
Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue

ClinicalTrials.gov processed this record on September 22, 2014