Alanosine in Treating Patients With Progressive or Recurrent Malignant Gliomas

Brain and Central Nervous System Tumors Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00075894
• Other study ID #: CDR0000349473
• Secondary ID: NABTT-0303
• Status: Completed
• Phase: Phase 1
• First received: January 9, 2004
• Last updated: January 10, 2009
• Start date: March 2004

Study information

• Verified date: August 2006
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain and Central Nervous System Tumors
• Central Nervous System Neoplasms
• Nervous System Neoplasms

Intervention

Drug:
• L-alanosine

Locations

Country	Name	City	State
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Josephine Ford Cancer Center at Henry Ford Hospital	Detroit	Michigan
United States	H. Lee Moffitt Cancer Center and Research Institute at University of South Florida	Tampa	Florida
United States	Wake Forest University Comprehensive Cancer Center	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States,