Oral ST1481 in Adults With Malignant Glioma: A Phase I-II Clinical Trial


Phase 1/Phase 2
18 Years
N/A
Not Enrolling
Both
Brain and Central Nervous System Tumors

Thank you

Trial Information

Oral ST1481 in Adults With Malignant Glioma: A Phase I-II Clinical Trial


OBJECTIVES:

Primary

- Determine the maximum tolerated dose (MTD) of gimatecan in patients with recurrent or
progressive primary malignant glioma treated with or without concurrent enzyme-inducing
anticonvulsant drugs.

- Determine whether this drug has sufficient activity to warrant further development in
these patients. (phase II)

Secondary

- Determine the qualitative and quantitative toxic effects of this drug in these
patients.

- Determine the pharmacokinetic behaviors of this drug in these patients.

- Correlate the principal toxic effects with the pertinent pharmacokinetic parameters of
this drug in these patients.

- Determine the antitumor activity of this drug in these patients.

OUTLINE: This is an open-label, dose-escalation, multicenter study. Patients are stratified
according to the concurrent use of enzyme-inducing anticonvulsant drugs (yes vs no).

- Phase I: Patients receive oral gimatecan once daily on days 1-5. Courses repeat every
28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of gimatecan 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.

- Phase II: Patients receive gimatecan as in phase I at the MTD. Patients are followed
for at least 1 month and then every 2 months thereafter.

PROJECTED ACCRUAL: Approximately 30-83 patients (30-42 for phase I [15-21 per stratum] and
21-41 for phase II) will be accrued for this study within 24 months.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically confirmed malignant glioma (glioblastoma multiforme, anaplastic
astrocytoma, or anaplastic oligodendroglioma)

- Recurrent or progressive primary CNS neoplasm by contrast-enhanced MRI

- Tumor progression after prior surgery, radiotherapy, or chemotherapy

- Measurable or evaluable disease

- Failed prior standard curative or palliative therapy (phase I only)

PATIENT CHARACTERISTICS:

Age

- 18 and over

Performance status

- Karnofsky 60-100%

Life expectancy

- At least 3 months

Hematopoietic

- Absolute neutrophil count ≥ 2,000/mm^3

- Platelet count ≥ 100,000/mm^3

Hepatic

- SGPT and SGOT ≤ 1.5 times upper limit of normal (ULN) (3 times ULN if liver
metastases are present)

- Alkaline phosphatase ≤ 2.5 times ULN (5 times ULN if liver metastases are present)

- Bilirubin normal

Renal

- Creatinine ≤ 1.5 times ULN

Cardiovascular

- No myocardial infarction with the past year

- No heart failure (including cardiac insufficiency controlled by digitalis and
diuretics)

- No irreversible arrhythmias requiring permanent medication

- No uncontrolled hypertension

Gastrointestinal

- No gastrointestinal dysfunction that would alter absorption or motility, such as any
of the following:

- Active peptic ulcer

- Inflammatory bowel disease

- Known intolerance to lactose

- Malabsorption syndromes

- Intestinal sub-occlusion

Other

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective barrier contraception

- No active infection

- No mentally incapacitated patients

- No other concurrent severe disease that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

- No concurrent immunotherapy

Chemotherapy

- See Disease Characteristics

- At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas)

- No more than 1 prior chemotherapy regimen

- No other concurrent chemotherapy

Endocrine therapy

- Concurrent corticosteroids allowed if dose stable for the past 2 weeks

- No concurrent hormonal therapy

Radiotherapy

- See Disease Characteristics

- At least 4 weeks since prior radiotherapy

- No concurrent radiotherapy

Surgery

- See Disease Characteristics

- At least 3 weeks since prior surgical resection

- No prior gastrointestinal surgery that would affect drug absorption

Other

- More than 4 weeks since prior participation in any other investigational drug study

- More than 72 hours since prior systemic antibiotics

- No concurrent H2 antagonists, antacids, or proton pump inhibitors

- If any of these therapies are necessary, ≥ 3 hours must elapse after gimatecan
administration

- No other concurrent anticancer therapy

- No other concurrent investigational drugs

- No other concurrent immunosuppressive agents

Type of Study:

Interventional

Study Design:

Masking: Open Label, Primary Purpose: Treatment

Principal Investigator

Timothy F. Cloughesy, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Jonsson Comprehensive Cancer Center

Authority:

United States: Federal Government

Study ID:

CDR0000372874

NCT ID:

NCT00087061

Start Date:

May 2004

Completion Date:

Related Keywords:

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

Name

Location
Jonsson Comprehensive Cancer Center at UCLA Los Angeles, California  90095-1781