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

NCT00096265 | Terminated Phase 3 Results

• 5 other identifiers: NCI-2009-00720CDR0000389490RTOG 0320RTOG-0320U10CA021661
• Study Type: interventional
• Target: 126
• Locations: 2 countries
• Sites: 83

Brief Summary

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.

Conditions

Metastatic Malignant Neoplasm in the Brain; Recurrent Non-Small Cell Lung Carcinoma; Stage IV Non-Small Cell Lung Cancer AJCC v7

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  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.

  From randomization to date of death or last follow-up, up to 48.1 months. Analysis occurs after all patients have been potentially followed for 9 months.

Secondary Outcomes (6)

• Rate of CNS Progression (One Year)

  From randomization to last follow-up, up to 48.1 months. Analysis occurs after all patients have been potentially followed for 9 months.

• Quality-adjusted Survival as Measured by EuroQol 5-dimension Instrument

  From randomization to last follow-up, up to 48.1 months. Analysis occurs after all patients have been potentially followed for 9 months.

• Change in Functional Assessment of Cancer Therapy-Brain (FACT-Br) Score at 3 Months

  From randomization to three months.

• Change in Performance Status at Six Months

  From randomization to six months.

• Change in Steroid Dependence at Six Months

  From randomization to six months.

Study Arms (3)

Arm I

ACTIVE COMPARATOR

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; Radiation: Stereotactic Radiosurgery

Arm II

EXPERIMENTAL

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; Radiation: Stereotactic Radiosurgery; Drug: Temozolomide

Arm III

EXPERIMENTAL

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.

Radiation: 3-Dimensional Conformal Radiation Therapy; Drug: Erlotinib Hydrochloride; Radiation: Stereotactic Radiosurgery

Interventions

3-Dimensional Conformal Radiation Therapy RADIATION

Patients undergo radiation therapy once daily for approximately 3 weeks

Also known as: 3-dimensional radiation therapy, 3D CONFORMAL RADIATION THERAPY, 3D CRT, 3D-CRT, Conformal Therapy, Radiation Conformal Therapy

Arm I; Arm II; Arm III

Erlotinib Hydrochloride DRUG

Given orally

Also known as: Cp-358,774, OSI-774, Tarceva

Arm III

Stereotactic Radiosurgery RADIATION

Patients undergo surgery after radiation therapy

Also known as: Stereotactic External Beam Irradiation, stereotactic external-beam radiation therapy, stereotactic radiation therapy, Stereotactic Radiotherapy, stereotaxic radiation therapy, stereotaxic radiosurgery

Arm I; Arm II; Arm III

Temozolomide DRUG

Given orally

Also known as: CCRG-81045, Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-, M & B 39831, M and B 39831, Methazolastone, RP-46161, SCH 52365, Temcad, Temodal, Temodar, Temomedac

Arm II

Eligibility Criteria

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

You may qualify if:

• 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 not exceed 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead
• Radiation Therapy Oncology Group: collaborator

Study Sites (83)

Arizona Oncology Services Foundation

Scottsdale, Arizona, 85260, United States

Location

Scottsdale Health Care-Osborn

Scottsdale, Arizona, 85260, United States

Location

Providence Saint Joseph Medical Center/Disney Family Cancer Center

Burbank, California, 91505, United States

Location

Kaiser Permanente Los Angeles Medical Center

Los Angeles, California, 90027, United States

Location

Pomona Valley Hospital Medical Center

Pomona, California, 91767, United States

Location

Saint Mary's Hospital and Regional Medical Center

Grand Junction, Colorado, 81501, United States

Location

Christiana Care Health System-Christiana Hospital

Newark, Delaware, 19718, United States

Location

Baptist MD Anderson Cancer Center

Jacksonville, Florida, 32207, United States

Location

Integrated Community Oncology Network-Southside Cancer Center

Jacksonville, Florida, 32207, United States

Location

Baptist Medical Center South

Jacksonville, Florida, 32258, United States

Location

Integrated Community Oncology Network-Florida Cancer Center Beaches

Jacksonville Beach, Florida, 32250, United States

Location

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, 33136, United States

Location

21st Century Oncology-Orange Park

Orange Park, Florida, 32073, United States

Location

UF Cancer Center at Orlando Health

Orlando, Florida, 32806, United States

Location

21st Century Oncology-Palatka

Palatka, Florida, 32177, United States

Location

Bay Medical Center

Panama City, Florida, 32401, United States

Location

Integrated Community Oncology Network-Flager Cancer Center

Saint Augustine, Florida, 32086, United States

Location

Tallahassee Memorial HealthCare

Tallahassee, Florida, 32308, United States

Location

John B Amos Cancer Center

Columbus, Georgia, 31904, United States

Location

Saint Alphonsus Cancer Care Center-Boise

Boise, Idaho, 83706, United States

Location

Northwest Community Hospital

Arlington Heights, Illinois, 60005, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Ingalls Memorial Hospital

Harvey, Illinois, 60426, United States

Location

Saint John's Hospital

Springfield, Illinois, 62702, United States

Location

Parkview Hospital Randallia

Fort Wayne, Indiana, 46805, United States

Location

Franciscan Saint Margaret Health-Hammond Campus

Hammond, Indiana, 46320, United States

Location

IU Health Methodist Hospital

Indianapolis, Indiana, 46202, United States

Location

Finley Hospital

Dubuque, Iowa, 52001, United States

Location

Norton Suburban Hospital and Medical Campus

Louisville, Kentucky, 40207, United States

Location

University of Maryland/Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States

Location

Saint Agnes Hospital

Baltimore, Maryland, 21229, United States

Location

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

West Michigan Cancer Center

Kalamazoo, Michigan, 49007, United States

Location

Fairview Ridges Hospital

Burnsville, Minnesota, 55337, United States

Location

Mercy Hospital

Coon Rapids, Minnesota, 55433, United States

Location

Fairview-Southdale Hospital

Edina, Minnesota, 55435, United States

Location

Unity Hospital

Fridley, Minnesota, 55432, United States

Location

Abbott-Northwestern Hospital

Minneapolis, Minnesota, 55407, United States

Location

University of Minnesota/Masonic Cancer Center

Minneapolis, Minnesota, 55455, United States

Location

North Memorial Medical Health Center

Robbinsdale, Minnesota, 55422, United States

Location

Coborn Cancer Center at Saint Cloud Hospital

Saint Cloud, Minnesota, 56303, United States

Location

Saint Cloud Hospital

Saint Cloud, Minnesota, 56303, United States

Location

Metro Minnesota Community Oncology Research Consortium

Saint Louis Park, Minnesota, 55416, United States

Location

Park Nicollet Clinic - Saint Louis Park

Saint Louis Park, Minnesota, 55416, United States

Location

United Hospital

Saint Paul, Minnesota, 55102, United States

Location

Ridgeview Medical Center

Waconia, Minnesota, 55387, United States

Location

Saint Louis University Hospital

St Louis, Missouri, 63110, United States

Location

Nevada Cancer Research Foundation CCOP

Las Vegas, Nevada, 89106, United States

Location

Renown Regional Medical Center

Reno, Nevada, 89502, United States

Location

Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital

New Brunswick, New Jersey, 08903, United States

Location

Riverview Medical Center/Booker Cancer Center

Red Bank, New Jersey, 07701, United States

Location

Sparta Cancer Treatment Center

Sparta, New Jersey, 07871, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

Mission Hospital-Memorial Campus

Asheville, North Carolina, 28801, United States

Location

Summa Akron City Hospital/Cooper Cancer Center

Akron, Ohio, 44304, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Natalie Warren Bryant Cancer Center at Saint Francis

Tulsa, Oklahoma, 74136, United States

Location

Delaware County Memorial Hospital

Drexel Hill, Pennsylvania, 19026, United States

Location

Radiation Therapy Oncology Group

Philadelphia, Pennsylvania, 19103, United States

Location

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Reading Hospital

West Reading, Pennsylvania, 19611, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Thompson Cancer Survival Center

Knoxville, Tennessee, 37916, United States

Location

Arlington Cancer Center

Arlington, Texas, 76012, United States

Location

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, 75390, United States

Location

University of Texas Medical Branch

Galveston, Texas, 77555-0565, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Intermountain Medical Center

Murray, Utah, 84107, United States

Location

McKay-Dee Hospital Center

Ogden, Utah, 84403, United States

Location

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, 84112, United States

Location

LDS Hospital

Salt Lake City, Utah, 84143, United States

Location

Sentara Norfolk General Hospital

Norfolk, Virginia, 23507, United States

Location

Virginia Commonwealth University/Massey Cancer Center

Richmond, Virginia, 23298, United States

Location

Virginia Mason Medical Center

Seattle, Washington, 98101, United States

Location

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, 53792, United States

Location

Froedtert and the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Wheaton Franciscan Cancer Care - All Saints

Racine, Wisconsin, 53405, United States

Location

CancerCare Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada

Location

Ottawa Hospital-Civic Campus

Ottawa, Ontario, K1Y 4E9, Canada

Location

McGill University Department of Oncology

Montreal, Quebec, H2W 1S6, Canada

Location

MeSH Terms

Conditions

Brain Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

Radiotherapy, Conformal; Erlotinib Hydrochloride; Radiosurgery; Temozolomide

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring

Limitations and Caveats

This study stopped accrual early due to unmet targeted accrual goals with 126 subjects accrued out of 381 planned.

Results Point of Contact

• Title: Wendy Seiferheld
• Organization: Radiation Therapy Oncology Group

wseiferheld@acr.org

Study Officials

• Paul Sperduto

  Radiation Therapy Oncology Group

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 9, 2004
• First Posted: November 9, 2004
• Study Start: October 6, 2004
• Primary Completion: June 14, 2011
• Study Completion: April 1, 2012
• Last Updated: March 9, 2018
• Results First Posted: April 16, 2013

Record last verified: 2018-02

Locations

CA (3); US (80)