Alanosine in Treating Patients With Progressive or Recurrent Malignant Gliomas

Study Description

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Brief Summary:

RATIONALE: Drugs used in chemotherapy, such as alanosine, use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: This phase I trial is studying the side effects and best dose of alanosine in treating patients with high-grade progressive or recurrent malignant gliomas.

Condition or disease	Intervention/treatment	Phase
Brain and Central Nervous System Tumors	Drug: L-alanosine	Phase 1

Detailed Description:

OBJECTIVES:

• Determine the maximum tolerated dose of alanosine (SDX-102) with or without enzyme-inducible antiepileptic drugs (EIAEDs) in patients with methylthioadenosine phosphorylase (MTAP)-deficient high-grade progressive or recurrent malignant gliomas.
• Determine the pharmacokinetics of this drug administered concurrently with EIAEDs in these patients.

OUTLINE: This is an open-label, nonrandomized, multicenter, dose-escalation study. Patients are stratified according to concurrent anticonvulsant drug use (drugs that induce hepatic metabolic enzymes vs drugs that cause modest or no induction of hepatic metabolic enzymes OR no anticonvulsant drug).

Patients receive alanosine (SDX-102) IV continuously for 5 days. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of SDX-102 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.

After completion of study therapy, patients are followed at 1 week and then every 2 months thereafter.

PROJECTED ACCRUAL: A total of 18 patients will be accrued for this study.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	18 participants
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	A Phase I/II, Open-Label, Non-Randomized, Multicenter, Single Agent Study Of Intravenous SDX-102 For The Treatment Of Patients With MTAP-Deficient High Grade Recurrent Malignant Gliomas
Study Start Date :	March 2004

Arms and Interventions

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Outcome Measures

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Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed malignant glioma of 1 of the following types:

  • Anaplastic astrocytoma
  • Anaplastic oligodendroglioma
  • Glioblastoma multiforme

• Progressive or recurrent disease after prior radiotherapy with or without chemotherapy

  • Low-grade glioma that progressed after prior radiotherapy with or without chemotherapy and is found to be high-grade glioma after biopsy allowed
  • No more than 2 prior treatment regimens
• Measurable disease by CT scan or MRI
• Documented absence of methylthioadenosine phosphorylase (MTAP) on fixed tumor specimens

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Karnofsky 60-100%

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3

Hepatic

• Bilirubin ≤ 1.5 mg/dL
• Transaminases ≤ 4 times upper limit of normal

Renal

• Creatinine ≤ 1.5 mg/dL

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier contraception before, during, and for 4 weeks after study participation
• Mini mental state exam score of ≥ 15
• No psychological or sociological condition, addictive disorder, or family problem that would preclude study compliance
• No other malignancy within the past 5 years except curatively treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix or breast
• No concurrent serious infection or medical illness that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No concurrent prophylactic growth factors (e.g., filgrastim [G-CSF] or sargramostim [GM-CSF])

Chemotherapy

• See Disease Characteristics
• At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas)

Endocrine therapy

• Must be maintained on a stable or lower corticosteroid regimen from the time of the baseline scan until the start of study treatment
• No concurrent steroids as antiemetics

Radiotherapy

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

Surgery

• Not specified

Other

• Recovered from prior therapy
• More than 10 days since prior anticonvulsant drugs that induce hepatic metabolic enzymes
• No other concurrent investigational agents

Contacts and Locations

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Locations

United States, Florida
H. Lee Moffitt Cancer Center and Research Institute at University of South Florida
Tampa, Florida, United States, 33612-9497
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231-2410
United States, Massachusetts
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, United States, 02114
United States, Michigan
Josephine Ford Cancer Center at Henry Ford Hospital
Detroit, Michigan, United States, 48202
United States, North Carolina
Wake Forest University Comprehensive Cancer Center
Winston-Salem, North Carolina, United States, 27157-1096

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators

Study Chair:	Surasak Phuphanich, MD, FAAN	Emory University

More Information

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ClinicalTrials.gov Identifier:	NCT00075894 History of Changes
Other Study ID Numbers:	CDR0000349473; NABTT-0303
First Posted:	January 13, 2004
Last Update Posted:	January 13, 2009
Last Verified:	August 2006

Keywords provided by National Cancer Institute (NCI):

adult anaplastic oligodendroglioma; adult anaplastic astrocytoma; adult glioblastoma	recurrent adult brain tumor; adult giant cell glioblastoma; adult gliosarcoma

Additional relevant MeSH terms:

Glioma; Nervous System Neoplasms; Central Nervous System Neoplasms; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial	Neoplasms, Nerve Tissue; Neoplasms by Site; Nervous System Diseases; Alanosine; Antibiotics, Antineoplastic; Antineoplastic Agents; Chelating Agents; Sequestering Agents; Molecular Mechanisms of Pharmacological Action