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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


Phase 1
18 Years
N/A
Not Enrolling
Both
Brain and Central Nervous System Tumors

Thank you

Trial Information

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


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.

Inclusion 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

Type of Study:

Interventional

Study Design:

Masking: Open Label, Primary Purpose: Treatment

Principal Investigator

Surasak Phuphanich, MD, FAAN

Investigator Role:

Study Chair

Investigator Affiliation:

Winship Cancer Institute of Emory University

Authority:

United States: Federal Government

Study ID:

CDR0000349473

NCT ID:

NCT00075894

Start Date:

March 2004

Completion Date:

Related Keywords:

  • Brain and Central Nervous System Tumors
  • adult anaplastic oligodendroglioma
  • adult anaplastic astrocytoma
  • adult glioblastoma
  • recurrent adult brain tumor
  • adult giant cell glioblastoma
  • adult gliosarcoma
  • Nervous System Neoplasms
  • Central Nervous System Neoplasms
  • Glioma

Name

Location

Massachusetts General Hospital Cancer CenterBoston, Massachusetts  02114
Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsBaltimore, Maryland  21231-2410
Josephine Ford Cancer Center at Henry Ford HospitalDetroit, Michigan  48202
Wake Forest University Comprehensive Cancer CenterWinston-Salem, North Carolina  27157-1096
H. Lee Moffitt Cancer Center and Research Institute at University of South FloridaTampa, Florida  33612