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

NCT00238251 | Completed Phase 2 DMC

• 2 other identifiers: SAKK 70/03EU-20526
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 3

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.

Conditions

Lung Cancer; Metastatic Cancer

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Overall survival

  life-long

Secondary Outcomes (4)

• Time to progression

  28 days

• Time to neurological progression

  28 days

• Time to extracranial disease progression

  28 days

• Adverse events as measured at completion of study treatment

  28 days

Study Arms (2)

Arm I

ACTIVE COMPARATOR

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; Radiation: radiation therapy

Arm II

ACTIVE COMPARATOR

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; Radiation: radiation therapy

Interventions

gefitinib DRUG

Once daily during days 1-28

Arm I

temozolomide DRUG

Once daily on days 1-21

Arm II

radiation therapy RADIATION

Whole brain radiotherapy

Arm I; Arm II

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Swiss Cancer Institute: lead

Study Sites (3)

Oncology Institute of Southern Switzerland

Bellinzona, CH-6500, Switzerland

Location

Kantonsspital Graubuenden

Chur, CH-7000, Switzerland

Location

Centre Hospitalier Universitaire Vaudois

Lausanne, CH-1011, Switzerland

Location

Related Publications (1)

• 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.

  PMID: 22093943 RESULT

MeSH Terms

Conditions

Lung Neoplasms; Neoplasm Metastasis; Carcinoma, Non-Small-Cell Lung; Brain Neoplasms

Interventions

Gefitinib; Temozolomide; Radiotherapy

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Therapeutics

Study Officials

• Gianfranco Pesce, MD

  Istituto Oncologico della Svizzera Italiana - Ospedale San Giovanni

  STUDY CHAIR

• Roger Stupp, MD

  Centre Hospitalier Universitaire Vaudois

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 12, 2005
• First Posted: October 13, 2005
• Study Start: May 1, 2005
• Primary Completion: April 1, 2009
• Study Completion: November 1, 2010
• Last Updated: June 5, 2012

Record last verified: 2012-06

Locations

CH (3)