Radiation Therapy With or Without Thalidomide in Treating Patients With Brain Metastases

Sponsor
National Cancer Institute (NCI) (NIH)
Overall Status
Completed
CT.gov ID
NCT00033254
Collaborator
NRG Oncology (Other)
332
1
2

Study Details

Study Description

Brief Summary

Randomized phase III trial to compare the effectiveness of radiation therapy with or without thalidomide in treating patients who have brain metastases. Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs such as thalidomide may stop the growth of brain metastases by stopping blood flow to the tumor. It is not yet known whether radiation therapy is more effective with or without thalidomide in treating brain metastases.

Condition or Disease Intervention/Treatment Phase
  • Radiation: radiation therapy
  • Drug: thalidomide
  • Procedure: quality-of-life assessment
Phase 3

Detailed Description

OBJECTIVES:
  1. Compare the overall survival of patients with multiple brain metastases treated with radiotherapy with or without thalidomide.

  2. Compare the time to tumor progression in patients treated with these regimens.

  3. Compare the time to neuro-cognitive progression in patients treated with these regimens.

  4. Compare the cause of death distribution in patients treated with these regimens.

  5. Compare the frequency of toxic effects of these regimens in these patients. VI. Evaluate and compare the quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to recursive partitioning analysis class (I vs II) and planned chemotherapy after whole brain irradiation (yes vs no). Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients undergo radiotherapy once daily 5 days a week for 3 weeks. Arm II: Patients undergo radiotherapy as in arm I. Beginning on the first day of radiotherapy, patients receive oral thalidomide once daily.

Treatment with thalidomide continues for 2 years in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline, at completion of radiotherapy, and then every 2 months for 1 year.

Patients are followed every 2 months for 1 year, every 4 months for 1 year, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 332 patients (166 per treatment arm) will be accrued for this study within 14.5 months.

Study Design

Study Type:
Interventional
Actual Enrollment :
332 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase III Study of Conventional Radiation Therapy Plus Thalidomide (NSC#66847) Versus Conventional Radiation Therapy for Multiple Brain Metastases
Study Start Date :
Mar 1, 2002
Actual Primary Completion Date :
May 1, 2006

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Arm I (radiation therapy)

Patients undergo radiotherapy once daily 5 days a week for 3 weeks.

Radiation: radiation therapy
Undergo conventional radiation therapy
Other Names:
  • irradiation
  • radiotherapy
  • therapy, radiation
  • Procedure: quality-of-life assessment
    Ancillary studies
    Other Names:
  • quality of life assessment
  • Experimental: Arm II (radiation therapy, thalidomide)

    Patients undergo radiotherapy as in arm I. Beginning on the first day of radiotherapy, patients receive oral thalidomide once daily.

    Radiation: radiation therapy
    Undergo conventional radiation therapy
    Other Names:
  • irradiation
  • radiotherapy
  • therapy, radiation
  • Drug: thalidomide
    Given orally
    Other Names:
  • Kevadon
  • Synovir
  • THAL
  • Thalomid
  • Procedure: quality-of-life assessment
    Ancillary studies
    Other Names:
  • quality of life assessment
  • Outcome Measures

    Primary Outcome Measures

    1. Overall survival [Up to 6 years]

      The log-rank statistic will be used.

    2. Time to tumor progression [Date of randomization to documentation of progression, assessed up to 6 years]

      Cumulative incidence model will be used to analyze the data. A multivariate Cox model analysis will be performed.

    3. Time to neuro-cognitive progression as assessed by the Mini Mental State Exam [Up to 6 years]

      Cumulative incidence model will be used to analyze the data.

    Secondary Outcome Measures

    1. Cause of death distribution [Up to 6 years]

    2. Frequency of toxicities, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0 [Up to 6 years]

    3. Quality of life as measured by the Spitzer Quality of Life Index (SQLI) [6 months]

    4. Quality of life as measured by the SQLI [12 months]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Histologically confirmed extracranial primary malignancy

    • Multiple brain metastases

    • At least 1 measurable brain metastasis by MRI

    • More than 4.0 cm

    • Located in midbrain or brainstem (radiosurgery ineligible)

    • Performance status - Zubrod 0-1

    • At least 8 weeks

    • Absolute neutrophil count at least 1,500/mm^3

    • Platelet count at least 100,000/mm^3

    • Hemoglobin at least 11 g/dL*

    • Hematocrit at least 35%*

    • Bilirubin no greater than 1.5 mg/dL

    • ALT no greater than 2 times normal

    • Creatinine no greater than 1.5 mg/dL

    • BUN no greater than 25 mg/dL

    • No history of deep venous thrombosis

    • No sensory neuropathy grade 2 or greater

    • No known AIDS

    • No other major medical illness or psychiatric impairments that would preclude study therapy

    • Not pregnant or nursing

    • Negative pregnancy test

    • Fertile patients must use effective barrier method of contraception during and for at least 4 weeks after study

    • No prior thalidomide

    • More than 2 weeks since prior chemotherapy

    • Concurrent chemotherapy allowed if more than 6 weeks past study entry (allowed during first 6 weeks of study if disease progression occurs)

    • See Disease Characteristics

    • No prior radiotherapy to the head or neck

    • No prior radiosurgery

    • Prior resection of brain metastases allowed

    • No concurrent anticoagulant therapy

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Radiation Therapy Oncology Group Philadelphia Pennsylvania United States 19103

    Sponsors and Collaborators

    • National Cancer Institute (NCI)
    • NRG Oncology

    Investigators

    • Principal Investigator: Jonathan Knisely, Radiation Therapy Oncology Group

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT00033254
    Other Study ID Numbers:
    • NCI-2012-02461
    • RTOG-BR-0118
    • CDR0000069268
    • U10CA021661
    First Posted:
    Jan 27, 2003
    Last Update Posted:
    Oct 30, 2020
    Last Verified:
    Oct 1, 2020
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Oct 30, 2020