Thalidomide and Temozolomide in Relapsed or Progressive CNS Disease or Neuroblastoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00098865
Recruitment Status : Completed
First Posted : December 9, 2004
Results First Posted : September 25, 2014
Last Update Posted : October 7, 2014
National Cancer Institute (NCI)
Boston Children’s Hospital
Celgene Corporation
Information provided by (Responsible Party):
Mark W. Kieran, MD, PhD, Dana-Farber Cancer Institute

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.

Condition or disease Intervention/treatment Phase
Central Nervous System Tumor, Pediatric Neuroblastoma Drug: temozolomide Drug: thalidomide Phase 2

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%.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 15 participants
Intervention Model: Single Group Assignment
Masking: None (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
Study Start Date : September 2002
Actual Primary Completion Date : June 2010
Actual Study Completion Date : June 2010

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Neuroblastoma
U.S. FDA Resources

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. Therapy Completion Rate [ Time Frame: 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 Outcome Measures :
  1. Overall Response [ Time Frame: 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

  2. Overall Survival [ Time Frame: Assessed after treatment discontinued every 3 months up to 2 years. ]
    Time from registration to death. Patients alive at last follow-up were censored.

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Ages Eligible for Study:   up to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00098865

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

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 ( U.S. NIH Grant/Contract )
CDR0000396780 ( Registry Identifier: NCI PDQ )
First Posted: December 9, 2004    Key Record Dates
Results First Posted: September 25, 2014
Last Update Posted: October 7, 2014
Last Verified: September 2014

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