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

Alternate Title

Alanosine in Treating Patients With Progressive or Recurrent Malignant Gliomas

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Completed	18 and over	NCI	NABTT-0303 NCT00075894

Objectives

1. 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.
2. Determine the pharmacokinetics of this drug administered concurrently with EIAEDs in these patients.

Entry 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

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

Patient Characteristics:

Age

• 18 and over

Performance status

• Karnofsky 60-100%

Life expectancy

• Not specified

Hematopoietic

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

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

Expected Enrollment

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

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.

Trial Contact Information

Trial Lead Organizations

New Approaches to Brain Tumor Therapy

Surasak Phuphanich, MD, FAAN, Protocol chair		Ph: 404-778-5180; 888-946-7447

Registry Information
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
Trial Start Date		2004-03-06
Registered in ClinicalTrials.gov		NCT00075894
Date Submitted to PDQ		2003-12-09
Information Last Verified		2006-08-15
NCI Grant/Contract Number		CA062475

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