Radiation Therapy Combined With Either Gefitinib or Temozolomide in Pats With NSCLC and Brain Metastases

NCT ID: NCT00238251

Last Updated: 2012-06-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 59 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-05-31
• Study Completion Date: 2010-11-30

Brief Summary

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Gefitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving radiation therapy together with either gefitinib or temozolomide may kill more tumor cells.

PURPOSE: This randomized phase II trial is studying how well giving radiation therapy together with either gefitinib or temozolomide works in treating patients with non-small cell lung cancer and brain metastases.

Detailed Description

OBJECTIVES:

Primary

• Compare the efficacy of whole-brain radiotherapy combined with either gefitinib or temozolomide, in terms of overall survival, in patients with non-small cell lung cancer and brain metastases.

Secondary

• Compare the tolerability and toxicity of these regimens in these patients.
• Compare the time to neurological disease progression, time to extracranial disease progression, and time to overall disease progression, in patients treated with these regimens.
• Compare adverse events in patients treated with these regimens.
• Compare cognitive function and quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, open-label, parallel-group, multicenter study. Patients are stratified according to extracranial disease (yes vs no), number of brain metastases (1-3 vs ≥ 4), prior chemotherapy (yes vs no), WHO performance status (0-1 vs 2), and participating center. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients undergo whole-brain radiotherapy (WBRT) once daily on days 1-5 and 8-12 and receive oral gefitinib once daily on days 1-28. Gefitinib treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients undergo WBRT as in arm I and receive oral temozolomide once daily on days 1-21. Temozolomide treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline and on day 1 of courses 2, 3, and 5.

After completion of study therapy, patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 30-86 patients (15-43 per treatment arm) will be accrued for this study within 3 years.

Conditions

Lung Cancer; Metastatic Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm I

Patients undergo whole-brain radiotherapy (WBRT) once daily on days 1-5 and 8-12 and receive oral gefitinib once daily on days 1-28. Gefitinib treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity

Group Type: ACTIVE_COMPARATOR

gefitinib

Intervention Type: DRUG

Once daily during days 1-28

radiation therapy

Intervention Type: RADIATION

Whole brain radiotherapy

Arm II

Patients undergo WBRT as in arm I and receive oral temozolomide once daily on days 1-21. Temozolomide treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity

Group Type: ACTIVE_COMPARATOR

temozolomide

Intervention Type: DRUG

Once daily on days 1-21

radiation therapy

Intervention Type: RADIATION

Whole brain radiotherapy

Interventions

gefitinib

Once daily during days 1-28

Intervention Type: DRUG

temozolomide

Once daily on days 1-21

Intervention Type: DRUG

radiation therapy

Whole brain radiotherapy

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

• No other unstable or uncompensated respiratory disease that would preclude study participation

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 12 months after completion of study treatment
• No nausea, vomiting, inability to swallow whole tablets/capsules, or malabsorption syndrome that would preclude oral medication ingestion or absorption
• No psychiatric disorder that would preclude giving informed consent or study compliance
• No active infection
• No uncontrolled diabetes mellitus
• No other medical condition that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No prior temozolomide

Endocrine therapy

• Concurrent corticosteroids allowed provided dose has been stable or decreasing for ≥ 4 days before study entry

Radiotherapy

• No prior brain irradiation

Surgery

• Not specified

Other

• No prior gefitinib or erlotinib
• More than 30 days since prior investigational clinical trial participation
• No other concurrent experimental drugs
• No other concurrent anticancer therapy
• No concurrent treatment with any of the following:

• Phenytoin
• Carbamazepine
• Rifampin
• Barbiturates
• Hypericum perforatum (St. John's wort)
• Other enzyme-inducing anti-epileptic drugs or tuberculostatic treatments
• Any drug that contraindicates administration with study drugs

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Swiss Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gianfranco Pesce, MD

Role: STUDY_CHAIR

Istituto Oncologico della Svizzera Italiana - Ospedale San Giovanni

Roger Stupp, MD

Role: PRINCIPAL_INVESTIGATOR

Centre Hospitalier Universitaire Vaudois

Locations

Oncology Institute of Southern Switzerland

Bellinzona, , Switzerland

Kantonsspital Graubuenden

Chur, , Switzerland

Centre Hospitalier Universitaire Vaudois

Lausanne, , Switzerland

Countries

Switzerland

References

Pesce GA, Klingbiel D, Ribi K, Zouhair A, von Moos R, Schlaeppi M, Caspar CB, Fischer N, Anchisi S, Peters S, Cathomas R, Bernhard J, Kotrubczik NM, D'Addario G, Pilop C, Weber DC, Bodis S, Pless M, Mayer M, Stupp R. Outcome, quality of life and cognitive function of patients with brain metastases from non-small cell lung cancer treated with whole brain radiotherapy combined with gefitinib or temozolomide. A randomised phase II trial of the Swiss Group for Clinical Cancer Research (SAKK 70/03). Eur J Cancer. 2012 Feb;48(3):377-84. doi: 10.1016/j.ejca.2011.10.016. Epub 2011 Nov 15.

Reference Type: RESULT

PMID: 22093943 (View on PubMed)

Other Identifiers

EU-20526

Identifier Type: -

Identifier Source: secondary_id

SAKK 70/03

Identifier Type: -

Identifier Source: org_study_id