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
18 Years
N/A
Both
Lung Cancer, Metastatic Cancer
Trial Information
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
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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Overall survival
Outcome Time Frame:
life-long
Safety Issue:
No
Principal Investigator
Gianfranco Pesce, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Istituto Oncologico della Svizzera Italiana - Ospedale San Giovanni
Authority:
Switzerland: Swissmedic
Study ID:
SAKK 70/03
NCT ID:
NCT00238251
Start Date:
May 2005
Completion Date:
November 2010
Related Keywords:
- Lung Cancer
- Metastatic Cancer
- stage IV non-small cell lung cancer
- recurrent non-small cell lung cancer
- tumors metastatic to brain
- Lung Neoplasms
- Neoplasm Metastasis
- Neoplasms
- Neoplasms, Second Primary
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