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

Tumors Metastatic to Brain Clinical Trial

Official title:

A Phase III Study of Conventional Radiation Therapy Plus Thalidomide (NSC#66847) Versus Conventional Radiation Therapy for Multiple Brain Metastases

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00033254
• Other study ID #: NCI-2012-02461
• Secondary ID: RTOG-BR-0118CDR0
• Status: Completed
• Phase: Phase 3
• Start date: March 2002

Study information

• Verified date: October 2020
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 332
• Est. primary completion date: May 2006
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Neoplasm Metastasis
• Tumors Metastatic to Brain

Intervention

Radiation:
• radiation therapy
Undergo conventional radiation therapy

Drug:
• thalidomide
Given orally

Procedure:
• quality-of-life assessment
Ancillary studies

Locations

Country	Name	City	State
United States	Radiation Therapy Oncology Group	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)	NRG Oncology

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival	The log-rank statistic will be used.	Up to 6 years
Primary	Time to tumor progression	Cumulative incidence model will be used to analyze the data. A multivariate Cox model analysis will be performed.	Date of randomization to documentation of progression, assessed up to 6 years
Primary	Time to neuro-cognitive progression as assessed by the Mini Mental State Exam	Cumulative incidence model will be used to analyze the data.	Up to 6 years
Secondary	Cause of death distribution		Up to 6 years
Secondary	Frequency of toxicities, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0		Up to 6 years
Secondary	Quality of life as measured by the Spitzer Quality of Life Index (SQLI)		6 months
Secondary	Quality of life as measured by the SQLI		12 months