Temozolomide and Topotecan in Treating Patients With Primary CNS Lymphoma

Trial Information

Phase II Trial of Salvage Chemotherapy With Temozolomide in Combination With Topotecan for Primary CNS Lymphoma

OBJECTIVES:

Primary

- Determine the complete radiologic response rate in patients with primary CNS lymphoma
treated with salvage chemotherapy comprising temozolomide and topotecan.

Secondary

- Determine the median and failure-free survival of patients treated with this regimen.

- Determine the toxicity of this regimen in these patients.

- Determine the overall response rate in patients treated with this regimen.

OUTLINE: This is an open-label study.

Patients receive oral temozolomide once daily on days 1-5 and topotecan IV over 30 minutes
once daily on days 2-6. Treatment repeats every 28 days for 6-8 courses in the absence of
disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 1 year, every
4 months for 1 year, and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 6-25 patients will be accrued for this study.

Inclusion Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically confirmed primary CNS lymphoma at initial diagnosis

- Measurable tumor by radiography

- Failed* OR is not a candidate for first-line high-dose systemic methotrexate-based
chemotherapy with or without radiotherapy NOTE: *Failure is defined as relapse,
progression, or failure to achieve a complete response

PATIENT CHARACTERISTICS:

Age

- 18 and over

Performance status

- Karnofsky 50-100%

Life expectancy

- Not specified

Hematopoietic

- Absolute neutrophil count ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- Hemoglobin ≥ 9 g/dL

Hepatic

- SGOT and SGPT ≤ 3 times upper limit of normal

- Bilirubin ≤ 2.0 mg/dL

Renal

- Creatinine clearance > 40 mL/min

Other

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- HIV negative

- No known allergy to temozolomide or topotecan

- No other malignancy within the past 5 years except adequately treated basal cell or
squamous cell skin cancer or stage I or II cancer in complete remission

- No other major medical illness or psychiatric impairment that would preclude study
participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

- No concurrent prophylactic growth factors

Chemotherapy

- See Disease Characteristics

- At least 6 weeks since prior nitrosoureas

- At least 2 weeks since prior methotrexate

Endocrine therapy

- Not specified

Radiotherapy

- See Disease Characteristics

Surgery

- Not specified

Other

- Recovered from all prior therapy

- At least 4 weeks since prior non-nitrosourea cytotoxic drugs (except methotrexate)

- At least 4 weeks since prior systemic investigational agents

- At least 2 weeks since prior non-cytotoxic antitumor drugs

- No other concurrent antitumor therapy

EXCLUSION CRITERA

1. Patients who are pregnant or breastfeeding, or females of childbearing potential not
using adequate contraception.

2. Known allergy to temozolomide or topotecan.

3. Severe vomiting or other inability to administer medications orally.

4. Major medical illnesses or psychiatric impairment that in the investigator's opinion
will prevent administration or completion of the protocol therapy and/or will
interfere with follow-up.

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Rate of complete radiologic response (CR)

Outcome Time Frame:

July 2006

Safety Issue:

Principal Investigator

Pamela Z. New, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Baylor College of Medicine

Authority:

United States: Food and Drug Administration

Study ID:

CDR0000427313

NCT ID:

NCT00109798

Start Date:

March 2005

Completion Date: