Thalidomide and Temozolomide in Relapsed or Progressive CNS Disease or Neuroblastoma

Study Overview
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Brief Summary
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RATIONALE: Thalidomide may stop the growth of tumor cells by stopping blood flow to the tumor. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining thalidomide with temozolomide may kill more tumor cells. PURPOSE: This phase II trial is studying the effectiveness of combining thalidomide with temozolomide in treating young patients who have relapsed or progressive brain tumors or recurrent neuroblastoma.

Detailed Description
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OBJECTIVES: Primary Determine the feasibility of thalidomide and temozolomide in pediatric patients with relapsed or progressive poor prognosis brain tumors or recurrent neuroblastomas. Secondary Determine preliminarily evidence of biologic activity of this regimen in these patients. Determine the toxic effects of this regimen in these patients. STATISTICAL DESIGN: The primary data analysis will estimate the percentage of patients who can complete 6 months of therapy in the mixed population. With a target accrual of 20 patients the 90% confidence for the true feasibility rate will be no wider than 40%.

Official Title
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A Phase II Pilot Study Of Thalidomide With Temozolomide In Patients With Relapsed Or Progressive Brain Tumors Or Neuroblastoma

Conditions
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Central Nervous System Tumor, Pediatric, Neuroblastoma

Intervention / Treatment
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* Drug: temozolomide
* Drug: thalidomide


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed* diagnosis of 1 of the following: Poor prognosis brain tumor Relapsed or progressive disease No curative therapy exists Neuroblastoma Recurrent disease NOTE: *Histologic confirmation not required for brain stem glioma; patients with brain stem glioma must have clinical and radiographic evidence of disease Patients with brain stem glioma must have symptoms lasting < 3 months comprising cranial nerve deficits (often VI or VII) and/or ataxia and/or long tract signs PATIENT CHARACTERISTICS: Age 21 and under Performance status Karnofsky 50-100% OR Lansky 50-100% Life expectancy More than 2 months Hematopoietic Hemoglobin ≥ 9.0 g/dL Platelet count > 75,000/mm^3 WBC > 2,000/mm^3 Absolute neutrophil count > 1,000/mm^3 Hepatic Bilirubin ≤ 1.5 mg/dL SGOT and SGPT ≤ 2 times normal (SGOT ≤ 4 times normal for patients taking Zantac) Alkaline phosphatase ≤ 2 times normal No active hepatic disease ≥ grade 3 Renal Creatinine < 1.5 mg/dL OR Creatinine clearance ≥ 70 mL/min No active renal disease ≥ grade 3 Cardiovascular No active cardiac disease ≥ grade 3 Pulmonary No active pulmonary disease ≥ grade 3 Other Not pregnant or nursing Fertile patients must use effective contraception during and for 4 weeks after study participation Willing and able to participate in the System for Thalidomide Education and Prescription Safety (S.T.E.P.S.^®) program No active psychiatric disease ≥ grade 3 PRIOR CONCURRENT THERAPY: Biologic therapy Prior biologic therapy allowed No prior thalidomide Chemotherapy Prior chemotherapy allowed No prior temozolomide Endocrine therapy Concurrent steroids allowed Radiotherapy Prior radiotherapy allowed Surgery Prior surgery allowed Other Concurrent antiseizure medications allowed No other concurrent investigational agents

Ages Eligible for Study
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Maximum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Thalidomide and Temozolomide<br>Thalidomide: Oral thalidomide on days 1-28 of a 28 day cycle initiated at 3 mg/kg and increased to maximum dose of 24 mg/kg or 1000 mg as tolerated. Temozolomide: Oral temozolomide on days 1-5 of 28 day cycle given at 200 mg/m2 or 150 mg/m2 for patients who had previously received significant therapy to the bone marrow (chemotherapy or radiation) or cranial spinal radiation. Patients were treated for 6 cycles unless disease progression or excessive toxicity. Treatment could continue beyond 6 cycles if absent disease progression | Drug: temozolomide<br>* The lower 150/m2 Temozolomide dose was for patients who had previously received significant therapy to the bone marrow (chemotherapy or radiation) or cranial spinal raditation.<br>* Other names: Temodar;Drug: thalidomide<br>* Calculated dose was rounded down to the nearest 50mg, or up to 50mg if calculated dose was less than 50mg. Patients increased the daily dose by 50mg (one capsule) on a weekly basis unitl either unacceptable toxicity or a maximum dose.<br>* Other names: Thalamid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Therapy Completion Rate | Feasibility in this study was defined as completion of 6 months of thalidomide with temozolomide therapy. The corresponding therapy completion rate is defined as the proportion of patients who completed 6 months of therapy. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response | Overall response is the best response during 6 months of therapy measured by radiographic response. Complete Response (CR): Disappearance of all detectable tumors by imaging, if initially positive, as well as 2 consecutively negative CSF cytologic examinations (if the initial cytology was positive). Partial Response (PR): > 50% reduction in the sum of the products of the maximum perpendicular diameter of all measurable lesions; or 2 consecutively negative CSF cytologies and a < 50% reduction in tumor size. Stable Disease (SD): < 50% reduction in the sum of the products of the maximum perpendicular diameters of all measurable lesions, and persistently negative or positive CSF cytology Progressive Disease (PD): > 25% increase in the size of any measurable lesion, the appearance of a new radiographically demonstrable lesion, or the conversion of negative CSF cytology to positive, as confirmed by at least one repeat CSF cytology | Assessed every 8 weeks while on treatment and every 3 months for one year off-study | 
| Overall Survival | Time from registration to death. Patients alive at last follow-up were censored. | Assessed after treatment discontinued every 3 months up to 2 years. |