Gimatecan in Treating Patients With Recurrent or Progressive Primary Malignant Glioma

Brain and Central Nervous System Tumors Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00087061
• Other study ID #: SIGMATAU-ST-01-402
• Secondary ID: UCLA-0403029-01S
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: July 8, 2004
• Last updated: July 17, 2013
• Start date: May 2004
• Est. completion date: June 2005

Study information

• Verified date: May 2005
• 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 gimatecan, work in different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: This phase I/II trial is studying the side effects and best dose of gimatecan in treating patients with recurrent or progressive primary malignant glioma.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Est. completion date: June 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

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:
• gimatecan

Locations

Country	Name	City	State
United States	Jonsson Comprehensive Cancer Center at UCLA	Los Angeles	California

Sponsors (2)

Lead Sponsor	Collaborator
Jonsson Comprehensive Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States,