Temozolomide and Topotecan in Treating Patients With Primary CNS Lymphoma

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Drugs used in chemotherapy, such as temozolomide and topotecan, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. PURPOSE: This phase II trial is studying how well giving temozolomide together with topotecan works in treating patients with primary CNS lymphoma.

Detailed Description
-----------------
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.

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

Conditions
-----------------
Central Nervous System Tumors, Lymphoma

Intervention / Treatment
-----------------
* Drug: temozolomide
* Drug: topotecan hydrochloride


Participation Criteria
=================
Eligibility 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 Patients who are pregnant or breastfeeding, or females of childbearing potential not using adequate contraception. Known allergy to temozolomide or topotecan. Severe vomiting or other inability to administer medications orally. 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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Temozolomide, Topotecan<br>Patient will take on days 1-5 of a 28-days schedule. Take Topotecan on days 2-6 of the 28 day schedule | Drug: temozolomide<br>* Patient will take drug on day 1-5 of 28 day schedule<br>* Other names: Temodar;Drug: topotecan hydrochloride<br>* Patient will have IV on days 2-6 on a 28-day schedule<br>* Other names: Topotecan;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of complete radiologic response (CR) |  | July 2006 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median overall survival |  | July 2006 | 
| Failure-free survival |  | July 2006 | 
| Toxicity |  | July 2006 | 
| Overall response rate (CR and partial response) |  | July 2006 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
primary central nervous system non-Hodgkin lymphoma, primary central nervous system Hodgkin lymphoma