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

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00096265
First received: November 9, 2004
Last updated: May 5, 2014
Last verified: October 2011
  Purpose

This randomized phase III trial is studying whole-brain radiation therapy and stereotactic radiosurgery with or without temozolomide or erlotinib to see how well they work compared to whole-brain radiation therapy and stereotactic radiosurgery in treating patients with brain metastases secondary to non-small cell lung cancer. Radiation therapy uses high-energy x-rays to kill tumor cells. Stereotactic radiosurgery may be able to deliver x-rays directly to the tumor and cause less damage to normal tissue. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop tumor cells from dividing so they stop growing or die. Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth and by blocking blood flow to the tumor. It is not yet known whether radiation therapy and stereotactic radiosurgery are more effective with or without temozolomide or erlotinib in treating brain metastases.


Condition Intervention Phase
Recurrent Non-small Cell Lung Cancer
Stage IV Non-small Cell Lung Cancer
Tumors Metastatic to Brain
Drug: erlotinib hydrochloride
Radiation: 3-dimensional conformal radiation therapy
Radiation: stereotactic radiosurgery
Drug: temozolomide
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Overall Survival [ Time Frame: From randomizaton to date of death for last follow-up. Analysis occurs after all patients have been potentiall followed for 9 months. ] [ Designated as safety issue: No ]
    Survival time is defined as time from randomization to date of death from any cause and estimated by the Kaplan-Meier method. Patients last known to be alive are censored at date of last contact.


Secondary Outcome Measures:
  • Time to CNS Progression [ Time Frame: From the date of randomization to date of progression, death, or last follow-up. Analysis occurs at the same time as the primary outcome analysis. ] [ Designated as safety issue: No ]
    CNS progression will be defined as any increase in perpendicular bi-dimensional tumor area for any of the 1-3 tracked brain metastases, by any amount, or the appearance of any new brain metastasis on a follow-up MRI (SRS planning scan will not be used to evaluate CNS progression).

  • Quality-adjusted Survival as Measured by EuroQol 5-dimension Instrument [ Time Frame: From randomization to date of death or last follow-up. Analysis occurs after the primary outcome analysis. ] [ Designated as safety issue: No ]
    Compared between two treatment arms using a two-group t-test.

  • Change in Functional Assessment of Cancer Therapy-Brain Subscale Questionnaire [ Time Frame: From randomization to three months. ] [ Designated as safety issue: No ]
    Compared between two treatment arms using a two-group chi-squared test.

  • Change in Performance Status [ Time Frame: From randomization to six months. ] [ Designated as safety issue: No ]
    Compared between two treatment arms using a two-group chi-squared test.

  • Change in Steroid Dependence [ Time Frame: From randomization to six months. ] [ Designated as safety issue: No ]
    Compared between two treatment arms using a two-group chi-squared test.

  • Cause of Death (Neurologic vs Other) [ Time Frame: From randomization to date of death. ] [ Designated as safety issue: No ]
    Compared between two arms using a two-group chi-squared test. Summarized in a 2x2 frequency table.


Enrollment: 126
Study Start Date: October 2004
Study Completion Date: April 2012
Primary Completion Date: June 2011 (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, 8-12, and 15-19. Within 14 days after completion of WBRT, patients undergo stereotactic radiosurgery.
Radiation: 3-dimensional conformal radiation therapy
Patients undergo radiation therapy once daily for approximately 3 weeks
Other Names:
  • 3D conformal radiation therapy
  • 3D-CRT
Radiation: stereotactic radiosurgery
Patients undergo surgery after radiation therapy
Experimental: 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.
Radiation: 3-dimensional conformal radiation therapy
Patients undergo radiation therapy once daily for approximately 3 weeks
Other Names:
  • 3D conformal radiation therapy
  • 3D-CRT
Radiation: stereotactic radiosurgery
Patients undergo surgery after radiation therapy
Drug: temozolomide
Given orally
Other Names:
  • SCH 52365
  • Temodal
  • Temodar
  • TMZ
Experimental: 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.
Drug: erlotinib hydrochloride
Given orally
Other Names:
  • CP-358,774
  • erlotinib
  • OSI-774
Radiation: 3-dimensional conformal radiation therapy
Patients undergo radiation therapy once daily for approximately 3 weeks
Other Names:
  • 3D conformal radiation therapy
  • 3D-CRT
Radiation: stereotactic radiosurgery
Patients undergo surgery after radiation therapy

Detailed Description:

PRIMARY OBJECTIVES:

I. 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 OBJECTIVES:

I. Compare time to CNS progression in patients treated with these regimens. II. Compare quality-adjusted survival in patients treated with these regimens. III. Compare 3-month quality of life in patients treated with these regimens. IV. Compare the 6-month performance status of patients treated with these regimens.

V. Compare 6-month steroid dependence in patients treated with these regimens. VI. Compare cause of death (neurologic vs other) in patients treated with these regimens.

VII. Determine the effects of non-protocol chemotherapy in these patients.

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.

  Eligibility

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

Inclusion Criteria:

  • 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
  • Performance status - Zubrod 0-1
  • Hemoglobin ≥ 8 g/dL
  • Absolute neutrophil count ≥ 1,000/mm^3
  • Platelet count ≥ 100,000/mm^3
  • 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
  • Creatinine < 1.5 times ULN
  • No clinically active interstitial lung disease

    • Chronic stable asymptomatic radiographic changes allowed
  • 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
  • No concurrent immunotherapy
  • No concurrent biologic therapy, excluding growth factors and epoetin alfa
  • 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)
  • 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
  • No other concurrent therapy for brain metastases unless a recurrence is detected
  • 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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00096265

  Hide Study Locations
Locations
United States, California
Providence Saint Joseph Medical Center/Disney Family Cancer Center
Burbank, California, United States, 91505
Pomona Valley Hospital Medical Center
Pomona, California, United States, 91767
United States, Colorado
Saint Mary's Hospital and Regional Medical Center
Grand Junction, Colorado, United States, 81502
United States, Delaware
Christiana Care Health System-Christiana Hospital
Newark, Delaware, United States, 19718
United States, Florida
Edna Williams Cancer Center at the Baptist Cancer Institute
Jacksonville, Florida, United States, 32207
Cancer Specialists of North Florida-Southside
Jacksonville, Florida, United States, 32207
Cancer Specialists of North Florida-Beaches
Jacksonville Beach, Florida, United States, 32250
Cancer Specialists of North Florida-Baptist South
Jascksonville, Florida, United States, 32258
Cancer Specialists of North Florida-Orange Park
Orange Park, Florida, United States, 32073
UF Cancer Center at Orlando Health
Orlando, Florida, United States, 32806
Cancer Specialists of North Florida-Putnam
Palatka, Florida, United States, 32177
Cancer Specialists of North Florida-Saint Augustine
Saint Augustine, Florida, United States, 32086
Tallahassee Memorial HealthCare
Tallahassee, Florida, United States, 32308
United States, Georgia
John B Amos Cancer Center
Columbus, Georgia, United States, 31904
United States, Illinois
Northwest Community Hospital
Arlington Heights, Illinois, United States, 60005
Northwestern University
Chicago, Illinois, United States, 60611
United States, Indiana
Franciscan Saint Margaret Health-Hammond Campus
Hammond, Indiana, United States, 46320
IU Health Methodist Hospital
Indianapolis, Indiana, United States, 46202
United States, Maryland
University of Maryland/Greenebaum Cancer Center
Baltimore, Maryland, United States, 21201
United States, Massachusetts
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, United States, 02114
United States, Michigan
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
West Michigan Cancer Center
Kalamazoo, Michigan, United States, 49007
United States, Minnesota
Fairview Ridges Hospital
Burnsville, Minnesota, United States, 55337
Mercy Hospital
Coon Rapids, Minnesota, United States, 55433
Fairview-Southdale Hospital
Edina, Minnesota, United States, 55435
Unity Hospital
Fridley, Minnesota, United States, 55432
University of Minnesota Medical Center-Fairview
Minneapolis, Minnesota, United States, 55455
Abbott-Northwestern Hospital
Minneapolis, Minnesota, United States, 55407
North Memorial Medical Health Center
Robbinsdale, Minnesota, United States, 55422
Metro-Minnesota CCOP
Saint Louis Park, Minnesota, United States, 55416
Park Nicollet Clinic - Saint Louis Park
Saint Louis Park, Minnesota, United States, 55416
United Hospital
Saint Paul, Minnesota, United States, 55102
Ridgeview Medical Center
Waconia, Minnesota, United States, 55387
United States, Missouri
Saint Louis University Hospital
Saint Louis, Missouri, United States, 63110
United States, Nevada
Nevada Cancer Research Foundation CCOP
Las Vegas, Nevada, United States, 89106
United States, New Jersey
UMDNJ - Robert Wood Johnson University Hospital
New Brunswick, New Jersey, United States, 08903
Riverview Medical Center/Booker Cancer Center
Red Bank, New Jersey, United States, 07701
Sparta Cancer Treatment Center
Sparta, New Jersey, United States, 07871
United States, New York
University of Rochester
Rochester, New York, United States, 14642
United States, North Carolina
Mission Hospital-Memorial Campus
Asheville, North Carolina, United States, 28801
United States, Ohio
Summa Akron City Hospital/Cooper Cancer Center
Akron, Ohio, United States, 44304
Cleveland Clinic Foundation
Cleveland, Ohio, United States, 44195
United States, Pennsylvania
Delaware County Memorial Hospital
Drexel Hill, Pennsylvania, United States, 19026
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111
Radiation Therapy Oncology Group
Philadelphia, Pennsylvania, United States, 19103
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, United States, 19107
United States, Tennessee
Thompson Cancer Survival Center
Knoxville, Tennessee, United States, 37916
United States, Texas
University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75390
United States, Utah
Intermountain Medical Center
Murray, Utah, United States, 84157
McKay-Dee Hospital Center
Ogden, Utah, United States, 84403
LDS Hospital
Salt Lake City, Utah, United States, 84143
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, United States, 84112
United States, Virginia
Sentara Hospitals
Norfolk, Virginia, United States, 23507
United States, Washington
Virginia Mason CCOP
Seattle, Washington, United States, 98101
United States, Wisconsin
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, United States, 53792
Canada, Ontario
The Ottawa Hospital Cancer Centre (Ottawa Health Research Institute) Civic Campus
Ottawa, Ontario, Canada, K1Y 4E9
Canada, Quebec
McGill University Department of Oncology
Montreal, Quebec, Canada, H2W 1S6
Sponsors and Collaborators
Investigators
Principal Investigator: Paul Sperduto Radiation Therapy Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00096265     History of Changes
Other Study ID Numbers: NCI-2009-00720, NCI-2009-00720, CDR0000389490, RTOG 0320, RTOG 0320, RTOG-0320, U10CA021661
Study First Received: November 9, 2004
Results First Received: March 5, 2013
Last Updated: May 5, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Neoplasm Metastasis
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Neoplastic Processes
Pathologic Processes
Temozolomide
Dacarbazine
Erlotinib
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 August 27, 2014