Clinical trial NCT00033254: Radiation Therapy With or Without Thalidomide in Treating Patients With Brain Metastases
Official title: A Phase III Study of Conventional Radiation Therapy Plus Thalidomide (NSC#66847) Versus Conventional Radiation Therapy for Multiple Brain Metastases
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Tumors Metastatic to Brain
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: NRG Oncology
First posted: 2003-01-27
Enrollment: 332
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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 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

Primary outcomes:
measure: Overall survival
timeFrame: Up to 6 years
measure: Time to tumor progression
timeFrame: Date of randomization to documentation of progression, assessed up to 6 years
measure: Time to neuro-cognitive progression as assessed by the Mini Mental State Exam
timeFrame: Up to 6 years
Secondary outcomes:
measure: Cause of death distribution
timeFrame: Up to 6 years
measure: Frequency of toxicities, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0
timeFrame: Up to 6 years
measure: Quality of life as measured by the Spitzer Quality of Life Index (SQLI)
timeFrame: 6 months
measure: Quality of life as measured by the SQLI
timeFrame: 12 months
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Radiation Therapy Oncology Group
state: Pennsylvania
Study officials:
affiliation: Radiation Therapy Oncology Group
name: Jonathan Knisely
role: PRINCIPAL_INVESTIGATOR
References: