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Last Modified: 5/9/2009     First Published: 10/25/2004  
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Phase III Randomized Study of Whole Brain Radiotherapy and Stereotactic Radiosurgery With Versus Without Temozolomide or Erlotinib in Patients With Non-Small Cell Lung Cancer and Brain Metastases

Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Radiation Therapy and Stereotactic Radiosurgery With or Without Temozolomide or Erlotinib in Treating Patients With Brain Metastases Secondary to Non-Small Cell Lung Cancer

Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase IIITreatmentActive18 and overNCIRTOG-0320
NCT00096265

Objectives

Primary

  1. Compare survival in patients with non-small cell lung cancer and brain metastases treated with whole brain radiotherapy and stereotactic radiosurgery with vs without temozolomide or erlotinib.

Secondary

  1. Compare time to CNS progression in patients treated with these regimens.
  2. Compare quality-adjusted survival in patients treated with these regimens.
  3. Compare 3-month quality of life in patients treated with these regimens.
  4. Compare the 6-month performance status of patients treated with these regimens.
  5. Compare 6-month steroid dependence in patients treated with these regimens.
  6. Compare cause of death (neurologic vs other) in patients treated with these regimens.
  7. Determine the effects of non-protocol chemotherapy in these patients.

Entry Criteria

Disease Characteristics:

  • Histologically confirmed non-small cell lung cancer


  • One to 3 intraparenchymal brain metastases by contrast-enhanced MRI, meeting the following criteria:
    • Well circumscribed tumor(s)
    • Maximum diameter ≤ 4.0 cm
      • If multiple lesions are present and one lesion is at the maximum diameter, the other lesions must be ≤ 3.0 cm in maximum diameter
    • No metastases within 10 mm of the optic apparatus such that a portion of the optic nerve or chiasm would be included in the high-dose stereotactic radiosurgery boost field
    • No metastases in the brainstem, midbrain, pons, or medulla


  • No prior complete resection of all known brain metastases
    • Subtotal resection allowed provided residual disease is ≤ 4.0 cm in maximum diameter


  • No clinical or radiographic evidence of progression (other than study lesion[s]) within the past month
    • Patients with brain metastases at initial presentation do not require 1 month of scans documenting stable disease


  • Stable extracranial metastases allowed
    • No known or pre-existing liver metastases


  • No leptomeningeal metastases by MRI or cerebrospinal fluid evaluation


  • Synchronous brain metastases at initial diagnosis allowed


Prior/Concurrent Therapy:

Biologic therapy

  • No concurrent immunotherapy
  • No concurrent biologic therapy, excluding growth factors and epoetin alfa

Chemotherapy

  • No prior temozolomide or erlotinib
  • No other concurrent chemotherapy during study radiotherapy
    • Other concurrent chemotherapy allowed after study radiotherapy, except for the following:
      • Temozolomide or erlotinib (arm I only)
      • Erlotinib (arm II only)
      • Temozolomide (arm III only)

Endocrine therapy

  • Not specified

Radiotherapy

  • No prior cranial radiotherapy
  • No concurrent intensity-modulated radiotherapy
  • Concurrent radiotherapy to painful bone lesions allowed
    • No concurrent radiotherapy to more than 15% of bone marrow

Surgery

  • See Disease Characteristics

Other

  • More than 30 days since prior investigational drugs
  • No concurrent enzyme-inducing antiepileptic drugs including, but not limited to, any of the following (for patients randomized to receive erlotinib):
    • Phenytoin
    • Carbamazepine
    • Rifampin
    • Phenobarbital
    • Primidone
    • Oxcarbazepine
  • No other concurrent investigational drugs
  • No concurrent Hypericum perforatum (St. John's wort)
  • No drugs that alter gastric pH (e.g., proton pump inhibitors or H2 antagonists) within 4 hours after erlotinib administration (arm III patients only)
  • No other concurrent therapy for brain metastases unless a recurrence is detected

Patient Characteristics:

Age

  • 18 and over

Performance status

  • Zubrod 0-1

Life expectancy

  • Not specified

Hematopoietic

  • Hemoglobin ≥ 8 g/dL
  • Absolute neutrophil count ≥ 1,000/mm3
  • Platelet count ≥ 100,000/mm3

Hepatic

  • AST < 2 times upper limit of normal (ULN)
  • Alkaline phosphatase < 2 times ULN unless due to elevated bone metastases
  • Total bilirubin normal
  • Lactic dehydrogenase < 2 times ULN

Renal

  • Creatinine < 1.5 times ULN

Pulmonary

  • No clinically active interstitial lung disease
    • Chronic stable asymptomatic radiographic changes allowed

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • HIV negative
  • Neurologic function status 0-2
  • No other major medical illness or psychiatric impairment that would preclude study participation
  • No history of allergic reaction attributed to compounds of similar chemical or biologic composition to erlotinib or temozolomide

Expected Enrollment

381

A total of 381 patients (127 per treatment arm) will be accrued for this study within 70 months.

Outcomes

Primary Outcome(s)

Overall survival

Secondary Outcome(s)

Time to CNS progression
Quality-adjusted survival as measured by EuroQol 5-dimension instrument
Change in Functional Assessment of Cancer Therapy-Brain subscale questionnaire at 3 months
Change in performance status at 6 months
Change in steroid dependence at 6 months
Cause of death (neurologic vs other)
Effects of non-protocol chemotherapy

Outline

This is a randomized, multicenter study. Patients are stratified according to age and the presence of extracranial metastases (< 65 years old AND no extracranial metastases vs ≥ 65 years old OR extracranial metastases), number of metastases (1 vs 2 or 3), and extent of extracranial disease (none vs present). Patients are randomized to 1 of 3 treatment arms.

  • Arm I: Patients undergo whole brain radiotherapy (WBRT) once daily on days 1-5, 8-12, and 15-19. Within 14 days after completion of WBRT, patients undergo stereotactic radiosurgery.


  • Arm II: Patients undergo WBRT and stereotactic radiosurgery as in arm I. Beginning on the first day of WBRT, patients receive oral temozolomide once daily on days 1-21. Beginning 4 weeks after completion of WBRT, patients may receive oral temozolomide alone once daily on days 1-5. Treatment with temozolomide repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.


  • Arm III: Patients undergo WBRT and stereotactic radiosurgery as in arm I. Beginning on the first day of WBRT, patients receive oral erlotinib once daily for up to 6 months.


In all arms, patients with recurrent brain metastases may undergo additional stereotactic radiosurgery.

Quality of life is assessed at baseline and at 3, 6, 9, 12, 18, and 24 months.

Patients are followed every 3 months for 2 years, every 6 months for 2 years, and then annually thereafter.

Trial Contact Information

Trial Lead Organizations

Radiation Therapy Oncology Group

Paul Sperduto, MD, MAPP, Protocol chair
Ph: 952-442-6000
Email: psperduto@mropa.com
Minesh Mehta, MD, Protocol co-chair
Ph: 608-263-5009; 800-622-8922
Email: mehta@humonc.wisc.edu
H. Robins, MD, PhD, Protocol co-chair
Ph: 608-263-1416; 800-622-8922
Email: hirobins@facstaff.wisc.edu

Trial Sites

U.S.A.
Arizona
  Scottsdale
 Virginia G. Piper Cancer Center at Scottsdale Healthcare - Osborn
 Clinical Trials Office - Virginia G. Piper Cancer Center
Ph: 480-323-1255
California
  Los Angeles
 Kaiser Permanente Medical Center - Los Angeles
 Michael Girvigian
Ph: 323-667-4011
800-954-8000
Florida
  Jacksonville
 Baptist Cancer Institute - Jacksonville
 Clinical Trials Office - Baptist Cancer Institute - Jacksonville
Ph: 904-202-7051
 Integrated Community Oncology Network at Southside Cancer Center
 Douglas Johnson, MD
Ph: 904-202-2273
  Jacksonville Beach
 Integrated Community Oncology Network
 Douglas Johnson, MD
Ph: 904-202-2273
  Jascksonville
 Baptist Medical Center South
 Douglas Johnson, MD
Ph: 904-202-2273
  Orange Park
 Integrated Community Oncology Network - Orange Park
 Douglas Johnson, MD
Ph: 904-202-2273
  Orlando
 M.D. Anderson Cancer Center at Orlando
 Alan Forbes, MD, PhD
Ph: 407-648-3800
  Palatka
 Florida Cancer Center - Palatka
 Douglas Johnson, MD
Ph: 904-202-2273
  Panama City
 Bay Medical
 Hasan Murshed
Ph: 850-747-6972
  Saint Augustine
 Flagler Cancer Center
 Douglas Johnson, MD
Ph: 904-202-2273
Georgia
  Columbus
 John B. Amos Cancer Center
 Clinical Trials Office - John B. Amos Cancer Center
Ph: 706-660-6404
Idaho
  Boise
 Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center
 Clinical Trials Office - Saint Alphonsus Cancer Care Center
Ph: 208-367-7954
Illinois
  Arlington Heights
 Northwest Community Hospital
 Stephen Nigh, MD
Ph: 847-618-6560
  Springfield
 Cancer Institute at St. John's Hospital
 Bruce Shevlin, MD
Ph: 217-525-5666
Indiana
  Fort Wayne
 Parkview Regional Cancer Center at Parkview Health
 David Hornback, MD
Ph: 574-647-7461
  Hammond
 Oncology Center at Saint Margaret Mercy Healthcare Center
 Urmi Kalokhe, MD
Ph: 219-933-2130
  Indianapolis
 Methodist Cancer Center at Methodist Hospital
 Contact Person
Ph: 317-962-8288
800-265-3220
Kentucky
  Louisville
 Norton Suburban Hospital
 Mark Cornett
Ph: 502-893-1000
Maryland
  Baltimore
 Greenebaum Cancer Center at University of Maryland Medical Center
 Clinical Trials Office - Greenebaum Cancer Center at University of Maryladn Medical Center
Ph: 800-888-8823
 St. Agnes Hospital Cancer Center
 Richard Hudes, MD
Ph: 410-368-2965
Michigan
  Ann Arbor
 University of Michigan Comprehensive Cancer Center
 Clinical Trials Office - University of Michigan Comprehensive Cancer Center
Ph: 800-865-1125
  Detroit
 Barbara Ann Karmanos Cancer Institute
 Clinical Trials Office - Barbara Ann Karmanos Cancer Institute
Ph: 313-576-9363
  Kalamazoo
 West Michigan Cancer Center
 Clinical Trials Office - West Michigan Cancer Center
Ph: 269-373-7458
Minnesota
  Burnsville
 Fairview Ridges Hospital
 Paul Sperduto, MD, MAPP
Ph: 952-442-6000
  Coon Rapids
 Mercy and Unity Cancer Center at Mercy Hospital
 Paul Sperduto, MD, MAPP
Ph: 952-442-6000
  Edina
 Fairview Southdale Hospital
 Clinical Trials Office - Fairview Southdale Hospital
Ph: 612-625-3650
  Fridley
 Mercy and Unity Cancer Center at Unity Hospital
 Paul Sperduto, MD, MAPP
Ph: 952-442-6000
  Minneapolis
 Virginia Piper Cancer Institute at Abbott - Northwestern Hospital
 Clinical Trials Office - Virginia Piper Cancer Institute
Ph: 612-863-5654
  Robbinsdale
 Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center
 Clinical Trials Office - Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center
Ph: 763-520-1893
  Saint Cloud
 CentraCare Clinic - River Campus
 Barbi Kaplan-Frenkel, DO
Ph: 320-229-4901
 Coborn Cancer Center
 Barbi Kaplan-Frenkel, DO
Ph: 320-229-4901
  Saint Louis Park
 CCOP - Metro-Minnesota
 Paul Sperduto, MD, MAPP
Ph: 952-442-6000
 Park Nicollet Cancer Center
 Paul Sperduto, MD, MAPP
Ph: 952-442-6000
  Saint Paul
 United Hospital
 Paul Sperduto, MD, MAPP
Ph: 952-442-6000
  Waconia
 Ridgeview Medical Center
 Paul Sperduto, MD, MAPP
Ph: 952-442-6000
Missouri
  Saint Louis
 Saint Louis University Cancer Center
 Clinical Trials Office - Saint Louis University Cancer Center
Ph: 314-977-4440
Nevada
  Las Vegas
 CCOP - Nevada Cancer Research Foundation
 John Ellerton, MD, CM
Ph: 702-384-0013
  Reno
 Renown Institute for Cancer at Renown Regional Medical Center
 Lawrence Dardick, MD
Ph: 775-982-5638
New Jersey
  Red Bank
 Booker Cancer Center at Riverview Medical Center
 Adnan Danish
Ph: 732-530-2382
  Sparta
 Frederick R. and Betty M. Smith Cancer Treatment Center
 Maria Werner-Wasik, MD
Ph: 215-955-7679
North Carolina
  Asheville
 Mission Hospitals - Memorial Campus
 Clinical Trials Office - Mission Hospitals - Memorial Campus
Ph: 828-213-4150
Ohio
  Akron
 Summa Center for Cancer Care at Akron City Hospital
 Clinical Trials Office - Akron City Hospital
Ph: 330-375-6101
  Cleveland
 Cleveland Clinic Taussig Cancer Center
 Clinical Trials Office - Cleveland Clinic Taussig Cancer Center
Ph: 866-223-8100
Pennsylvania
  Drexel Hill
 Delaware County Regional Cancer Center at Delaware County Memorial Hospital
 Rachelle Lanciano, MD
Ph: 610-284-8240
  Philadelphia
 Fox Chase Cancer Center - Philadelphia
 Clinical Trials Office - Fox Chase Cancer Center - Philadelphia
Ph: 215-728-4790
 Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
 Clinical Trials Office - Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
Ph: 215-955-6084
  Reading
 McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center
 Clinical Trials Office - McGlinn Family Regional Cancer Center
Ph: 610-988-9323
South Carolina
  Charleston
 Hollings Cancer Center at Medical University of South Carolina
 Clinical Trials Office - Hollings Cancer Center at Medical University of South Carolina
Ph: 843-792-9321
Texas
  Dallas
 Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
 Clinical Trials Office - Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
Ph: 866-460-4673; 214-648-7097
  Galveston
 University of Texas Medical Branch
 Clinical Trials Office - University of Texas Medical Branch
Ph: 409-772-1950
  Houston
 M. D. Anderson Cancer Center at University of Texas
 Clinical Trials Office - M. D. Anderson Cancer Center at the University of Texas
Ph: 713-792-3245
Utah
  Murray
 Jon and Karen Huntsman Cancer Center at Intermountain Medical Center
 R. Jeffrey Lee, MD
Ph: 801-408-1146
Washington
  Seattle
 CCOP - Virginia Mason Research Center
 Huong Pham, MD
Ph: 206-223-6801
Wisconsin
  Madison
 University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
 Clinical Trials Office - University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
Ph: 608-262-5223
  Milwaukee
 Medical College of Wisconsin Cancer Center
 Clinical Trials Office - Medical College of Wisconsin Cancer Center
Ph: 414-805-4380
Canada
Manitoba
  Winnipeg
 CancerCare Manitoba
 Ahmet Leylek
Ph: 204-787-2241
Ontario
  Ottawa
 Ottawa Hospital Regional Cancer Centre - General Campus
 Gad Perry
Ph: 613-737-7700 ext. 70209
888-627-5346

Registry Information
Official Title A Phase III Trial Comparing Whole Brain Radiation And Stereotactic Radiosurgery Alone Versus With Temozolomide Or Erlotinib In Patients With Non-Small Cell Lung Cancer And 1-3 Brain Metastases
Trial Start Date 2004-10-06
Trial Completion Date 2015-12-31 (estimated)
Registered in ClinicalTrials.gov NCT00096265
Date Submitted to PDQ 2004-08-27
Information Last Verified 2009-05-09
NCI Grant/Contract Number CA21661

Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol.

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