Thalidomide and Temozolomide in Relapsed or Progressive CNS Disease or Neuroblastoma

Neuroblastoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00098865
• Other study ID #: 01-279 DFCI
• Secondary ID: P30CA006516CDR00
• Status: Completed
• Phase: Phase 2
• First received: December 8, 2004
• Last updated: September 28, 2014
• Start date: September 2002
• Est. completion date: June 2010

Study information

• Verified date: September 2014
• Source: Dana-Farber Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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%.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: June 2010
• Est. primary completion date: June 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 21 Years

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Central Nervous System Neoplasms
• Central Nervous System Tumor, Pediatric
• Nervous System Neoplasms
• Neuroblastoma

Intervention

Drug:
• 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.
• 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.

Locations

Country	Name	City	State
United States	Dana Farber Cancer Institute	Boston	Massachusetts

Sponsors (4)

Lead Sponsor	Collaborator
Dana-Farber Cancer Institute	Celgene Corporation, Children's Hospital Boston, National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	6 months	Yes
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	Assessed every 8 weeks while on treatment and every 3 months for one year off-study	No
Secondary	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.	No