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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00033254
First received: April 9, 2002
Last updated: June 5, 2013
Last verified: June 2013
  Purpose

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 Intervention Phase
Tumors Metastatic to Brain
Radiation: radiation therapy
Drug: thalidomide
Procedure: quality-of-life assessment
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Overall survival [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
    The log-rank statistic will be used.

  • Time to tumor progression [ Time Frame: Date of randomization to documentation of progression, assessed up to 6 years ] [ Designated as safety issue: No ]
    Cumulative incidence model will be used to analyze the data. A multivariate Cox model analysis will be performed.

  • Time to neuro-cognitive progression as assessed by the Mini Mental State Exam [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
    Cumulative incidence model will be used to analyze the data.


Secondary Outcome Measures:
  • Cause of death distribution [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
  • Frequency of toxicities, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0 [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
  • Quality of life as measured by the Spitzer Quality of Life Index (SQLI) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Quality of life as measured by the SQLI [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Enrollment: 332
Study Start Date: March 2002
Primary Completion Date: May 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: quality of life assessment

Detailed Description:

OBJECTIVES:

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

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

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

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

V. 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00033254

Locations
United States, Pennsylvania
Radiation Therapy Oncology Group
Philadelphia, Pennsylvania, United States, 19103
Sponsors and Collaborators
Investigators
Principal Investigator: Jonathan Knisely Radiation Therapy Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00033254     History of Changes
Other Study ID Numbers: NCI-2012-02461, RTOG-BR-0118, CDR0000069268, RTOG-DEV-1006, U10CA021661
Study First Received: April 9, 2002
Last Updated: June 5, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Thalidomide
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents

ClinicalTrials.gov processed this record on September 18, 2014