Central Nervous System Tumor, Pediatric, Neuroblastoma
Conditions
Brief summary
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
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%.
Interventions
DRUGtemozolomide
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.
DRUGthalidomide
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.
Sponsors
National Cancer Institute (NCI)
Boston Children's Hospital
Celgene Corporation
Dana-Farber Cancer Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 21 Years
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Therapy Completion Rate | 6 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response | Assessed every 8 weeks while on treatment and every 3 months for one year off-study | 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 |
| Overall Survival | Assessed after treatment discontinued every 3 months up to 2 years. | Time from registration to death. Patients alive at last follow-up were censored. |
Countries
United States
Participant flow
Recruitment details
15 patients were enrolled between 2002 to 2007 at the Dana-Farber Cancer Institute.
Pre-assignment details
For pediatric patients with relapsed or progressive brain tumors and neuroblastoma.
Participants by arm
| Arm | Count |
|---|---|
| Thalidomide and Temozolomide 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. | 15 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Alternative Therapy | 1 |
| Overall Study | Progressive Disease | 6 |
Baseline characteristics
| Characteristic | Thalidomide and Temozolomide |
|---|---|
| Age, Categorical <=18 years | 14 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants |
| Disease Type Brain Tumor | 8 participants |
| Disease Type Neuroblastoma | 7 participants |
| Region of Enrollment United States | 15 participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 14 / 15 |
| serious Total, serious adverse events | 9 / 15 |
Outcome results
Primary
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.
Time frame: 6 months
Population: The analysis dataset is comprised of all treated patients.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Thalidomide and Temozolomide | Therapy Completion Rate | .40 proportion of participants |
Secondary
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
Time frame: Assessed every 8 weeks while on treatment and every 3 months for one year off-study
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Thalidomide and Temozolomide | Overall Response | Partial Response | 1 participants |
| Thalidomide and Temozolomide | Overall Response | Stable Disease | 9 participants |
| Thalidomide and Temozolomide | Overall Response | Progressive Disease | 4 participants |
| Thalidomide and Temozolomide | Overall Response | Unevaluable | 1 participants |
Secondary
Overall Survival
Time from registration to death. Patients alive at last follow-up were censored.
Time frame: Assessed after treatment discontinued every 3 months up to 2 years.
Population: The analysis dataset is comprised of all treated patients.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Thalidomide and Temozolomide | Overall Survival | 12.8 months |