Radiation Therapy Combined With Either Gefitinib or Temozolomide in Pats With NSCLC and Brain Metastases - Full Text View

Purpose

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.

Condition	Intervention	Phase
Lung Cancer Metastatic Cancer	Drug: gefitinib Drug: temozolomide Radiation: radiation therapy	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Whole Brain Radiotherapy in Combination With Gefitinib (Iressa) or Temozolomide (Temodal) for Brain Metastases From Non-Small Lung Cancer (NSCLC) A Randomized Phase II Trial

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lung Cancer

Drug Information available for: Temozolomide Gefitinib

U.S. FDA Resources

Further study details as provided by Swiss Group for Clinical Cancer Research:

Primary Outcome Measures:

Overall survival [ Time Frame: life-long ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Time to progression [ Time Frame: 28 days ] [ Designated as safety issue: No ]
Time to neurological progression [ Time Frame: 28 days ] [ Designated as safety issue: No ]
Time to extracranial disease progression [ Time Frame: 28 days ] [ Designated as safety issue: No ]
Adverse events as measured at completion of study treatment [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]

Enrollment:	59
Study Start Date:	May 2005
Study Completion Date:	November 2010
Primary Completion Date:	April 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: 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	Drug: gefitinib Once daily during days 1-28 Radiation: radiation therapy Whole brain radiotherapy
Active Comparator: 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	Drug: temozolomide Once daily on days 1-21 Radiation: radiation therapy Whole brain radiotherapy

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.

Eligibility

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

Criteria

DISEASE CHARACTERISTICS:

Histologically or cytologically confirmed non-small cell lung cancer AND newly diagnosed brain metastases meeting 1 of the following criteria:
- Multiple brain metastases
- Single brain metastasis not amenable to potentially curative treatment
No advanced extracranial disease severely compromising vital functions and performance

PATIENT CHARACTERISTICS:

Age

18 and over

Performance status

WHO 0-2

Life expectancy

Not specified

Hematopoietic

Hemoglobin > 10 g/dL
Absolute neutrophil count > 1,500/mm^3
Platelet count > 100,000/mm^3

Hepatic

Bilirubin ≤ 1.5 times upper limit of normal (ULN)
AST and ALT ≤ 2.5 times ULN
Alkaline phosphatase ≤ 2.5 times ULN (5 times ULN in the presence of documented bone metastases)
No unstable or uncompensated hepatic disease that would preclude study participation

Renal

Creatinine clearance ≥ 40 mL/min
No unstable or uncompensated renal disease that would preclude study participation

Cardiovascular

No myocardial infarction within the past 3 months
No unstable or uncompensated cardiac disease that would preclude study participation

Pulmonary

No clinically active interstitial lung disease
- Patients with chronic stable radiographic changes who are asymptomatic eligible
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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00238251

Locations

Switzerland
Oncology Institute of Southern Switzerland
Bellinzona, Switzerland, CH-6500
Kantonsspital Graubuenden
Chur, Switzerland, CH-7000
Centre Hospitalier Universitaire Vaudois
Lausanne, Switzerland, CH-1011

Sponsors and Collaborators

Swiss Group for Clinical Cancer Research

Investigators

Study Chair:	Gianfranco Pesce, MD	Istituto Oncologico della Svizzera Italiana - Ospedale San Giovanni
Principal Investigator:	Roger Stupp, MD	Centre Hospitalier Universitaire Vaudois

More Information

Publications:

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. Epub 2011 Nov 15.

Responsible Party:	Swiss Group for Clinical Cancer Research
ClinicalTrials.gov Identifier:	NCT00238251 History of Changes
Other Study ID Numbers:	SAKK 70/03, EU-20526
Study First Received:	October 12, 2005
Last Updated:	June 4, 2012
Health Authority:	Switzerland: Swissmedic

Keywords provided by Swiss Group for Clinical Cancer Research:

stage IV non-small cell lung cancer
recurrent non-small cell lung cancer
tumors metastatic to brain

Additional relevant MeSH terms:

Lung Neoplasms
Neoplasm Metastasis
Neoplasms
Neoplasms, Second Primary
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Neoplastic Processes
Pathologic Processes

Temozolomide
Dacarbazine
Gefitinib
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Protein Kinase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on May 19, 2013