Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

EMD 121974 in Treating Patients With Progressive or Recurrent Glioma

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II, Phase I Treatment Completed 18 and over NCI NABTT-9911 JHOC-NABTT-9911, NCT00006093, NABTT-9911

Objectives

1. Determine the maximum tolerated dose and dose-limiting toxicity of EMD 121974 in patients with progressive or recurrent malignant glioma.
2. Determine the 6-month progression-free survival, clinical response rate, duration of progression-free survival, and overall survival in patients treated with this drug.
3. Determine the effects of this drug on tumor perfusion, measured with magnetic resonance perfusion scan, and markers for angiogenesis in these patients.

Entry Criteria

Disease Characteristics:

• Histologically confirmed malignant glioma that is progressive or recurrent after radiotherapy and/or chemotherapy
  • Eligible subtypes:
    • Anaplastic astrocytoma
    • Anaplastic oligodendroglioma
    • Glioblastoma multiforme
  • Prior low-grade glioma that has progressed to a high-grade glioma (by biopsy) after radiotherapy and/or chemotherapy allowed



• Measurable disease by volumetric and magnetic resonance perfusion scan



• Prior biopsy or resection of recurrent brain tumor allowed

Prior/Concurrent Therapy:

Biologic therapy:

• No concurrent filgrastim (G-CSF)

Chemotherapy:

• See Disease Characteristics
• At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas) and recovered
• No more than 2 prior chemotherapy regimens

Endocrine therapy:

• Prior corticosteroids allowed if on stable dose for at least 5 days prior to study
• Concurrent corticosteroids (e.g., dexamethasone) allowed as clinically needed

Radiotherapy:

• See Disease Characteristics
• At least 3 months since prior radiotherapy and recovered

Surgery:

• See Disease Characteristics
• At least 1 week since prior surgery and recovered
• No concurrent elective surgery or dental extractions

Other:

• No other concurrent investigational agents

Patient Characteristics:

Age:

• 18 and over

Performance status:

• Karnofsky 60-100%

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm³
• Platelet count at least 100,000/mm³

Hepatic:

• Bilirubin normal
• Transaminases no greater than 2.5 times upper limit of normal

Renal:

• Creatinine no greater than 1.5 mg/dL

  OR

• Creatinine clearance at least 60 mL/min

Cardiovascular:

• No advanced coronary artery disease

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No serious concurrent infection or medical illness that would preclude study
• No other malignancy within the past 5 years except curatively treated carcinoma in situ or basal cell skin cancer
• No history of wound healing disorders
• No peptic ulcer disease within the past year
• Mini mental score of at least 15
• Willing and able to undergo MRI

Expected Enrollment

A minimum of 6 patients will be accrued for phase I of this study within 2-3 months. A total of 23-38 patients will be accrued for phase II of this study within 5-10 months.

Outline

This is a dose-escalation, multicenter 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 6-12 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 more than 2 of 6 or 4 of 12 patients experience dose-limiting toxicity. Once the MTD is determined, additional patients are treated at the MTD.

Patients are followed every 2 months.

Nabors LB, Mikkelsen T, Rosenfeld SS, et al.: Phase I and correlative biology study of cilengitide in patients with recurrent malignant glioma. J Clin Oncol 25 (13): 1651-7, 2007.[PUBMED Abstract]

Nabors LB, Rosenfeld SS, Mikkelsen T, et al.: NABTT 9911: a phase I trial of EMD 121974 for treatment of patients with recurrent malignant gliomas. [Abstract] Neuro-Oncology 6 (4): TA-39, 379, 2004.

Trial Contact Information

Trial Lead Organizations

New Approaches to Brain Tumor Therapy

Louis Nabors, MD, Protocol chair		Ph: 205-937-1842 Email: bnabors@uab.edu

Registry Information
Official Title		A Phase I/II Trial of EMD 121974 for Treatment of Patients with Recurrent Anaplastic Gliomas
Trial Start Date		2000-09-21
Registered in ClinicalTrials.gov		NCT00006093
Date Submitted to PDQ		2000-06-26
Information Last Verified		2003-04-01
NCI Grant/Contract Number		CA006973, CA062475