Thalidomide and Temozolomide in Relapsed or Progressive CNS Disease or Neuroblastoma

This study has been completed.
National Cancer Institute (NCI)
Children's Hospital Boston
Celgene Corporation
Information provided by (Responsible Party):
Mark W. Kieran, MD, PhD, Dana-Farber Cancer Institute Identifier:
First received: December 8, 2004
Last updated: September 28, 2014
Last verified: September 2014

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.

Condition Intervention Phase
Central Nervous System Tumor, Pediatric
Drug: temozolomide
Drug: thalidomide
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Pilot Study Of Thalidomide With Temozolomide In Patients With Relapsed Or Progressive Brain Tumors Or Neuroblastoma

Resource links provided by NLM:

Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • Therapy Completion Rate [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    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 Outcome Measures:
  • Overall Response [ Time Frame: Assessed every 8 weeks while on treatment and every 3 months for one year off-study ] [ Designated as safety issue: No ]

    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 [ Time Frame: Assessed after treatment discontinued every 3 months up to 2 years. ] [ Designated as safety issue: No ]
    Time from registration to death. Patients alive at last follow-up were censored.

Enrollment: 15
Study Start Date: September 2002
Study Completion Date: June 2010
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Thalidomide and Temozolomide


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.


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
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.
Other Name: Temodar
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.
Other Name: Thalamid

Detailed Description:



  • Determine the feasibility of thalidomide and temozolomide in pediatric patients with relapsed or progressive poor prognosis brain tumors or recurrent neuroblastomas.


  • 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%.


Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No


  • 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



  • 21 and under

Performance status

  • Karnofsky 50-100% OR
  • Lansky 50-100%

Life expectancy

  • More than 2 months


  • Hemoglobin ≥ 9.0 g/dL
  • Platelet count > 75,000/mm^3
  • WBC > 2,000/mm^3
  • Absolute neutrophil count > 1,000/mm^3


  • 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


  • Creatinine < 1.5 mg/dL OR
  • Creatinine clearance ≥ 70 mL/min
  • No active renal disease ≥ grade 3


  • No active cardiac disease ≥ grade 3


  • No active pulmonary disease ≥ grade 3


  • 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


Biologic therapy

  • Prior biologic therapy allowed

    • No prior thalidomide


  • Prior chemotherapy allowed

    • No prior temozolomide

Endocrine therapy

  • Concurrent steroids allowed


  • Prior radiotherapy allowed


  • Prior surgery allowed


  • Concurrent antiseizure medications allowed
  • No other concurrent investigational agents
  Contacts and Locations
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Please refer to this study by its identifier: NCT00098865

United States, Massachusetts
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Dana-Farber Cancer Institute
National Cancer Institute (NCI)
Children's Hospital Boston
Celgene Corporation
Study Chair: Mark W. Kieran, MD, PhD Dana-Farber Cancer Institute
  More Information

Responsible Party: Mark W. Kieran, MD, PhD, Principal Investigator, Dana-Farber Cancer Institute Identifier: NCT00098865     History of Changes
Other Study ID Numbers: 01-279 DFCI  P30CA006516  CDR0000396780 
Study First Received: December 8, 2004
Results First Received: December 15, 2012
Last Updated: September 28, 2014
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Nervous System Diseases
Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive
Neuroectodermal Tumors, Primitive, Peripheral
Alkylating Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Bacterial Agents
Anti-Infective Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Growth Inhibitors
Growth Substances
Immunologic Factors
Immunosuppressive Agents
Leprostatic Agents
Molecular Mechanisms of Pharmacological Action processed this record on May 26, 2016