Thalidomide and Temozolomide in Relapsed or Progressive CNS Disease or Neuroblastoma

NCT ID: NCT00098865

Last Updated: 2014-10-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-09-30
• Study Completion Date: 2010-06-30

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%.

Conditions

Central Nervous System Tumor, Pediatric; Neuroblastoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

temozolomide

Intervention Type: DRUG

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.

thalidomide

Intervention Type: DRUG

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.

Interventions

temozolomide

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.

Intervention Type: DRUG

thalidomide

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.

Intervention Type: DRUG

Other Intervention Names

Temodar; Thalamid

Eligibility Criteria

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

• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Boston Children's Hospital

OTHER

Sponsor Role: collaborator

Celgene Corporation

INDUSTRY

Sponsor Role: collaborator

Dana-Farber Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Mark W. Kieran, MD, PhD

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mark W. Kieran, MD, PhD

Role: STUDY_CHAIR

Dana-Farber Cancer Institute

Locations

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Countries

United States

Other Identifiers

P30CA006516

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CDR0000396780

Identifier Type: REGISTRY

Identifier Source: secondary_id

01-279 DFCI

Identifier Type: -

Identifier Source: org_study_id