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

NCT ID: NCT00096265

Last Updated: 2018-03-09

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 126 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-10-06
• Study Completion Date: 2012-04-01

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.

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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

3-Dimensional Conformal Radiation Therapy

Intervention Type: RADIATION

Patients undergo radiation therapy once daily for approximately 3 weeks

Stereotactic Radiosurgery

Intervention Type: RADIATION

Patients undergo surgery after radiation therapy

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.

Group Type: EXPERIMENTAL

3-Dimensional Conformal Radiation Therapy

Intervention Type: RADIATION

Patients undergo radiation therapy once daily for approximately 3 weeks

Stereotactic Radiosurgery

Intervention Type: RADIATION

Patients undergo surgery after radiation therapy

Temozolomide

Intervention Type: DRUG

Given orally

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.

Group Type: EXPERIMENTAL

3-Dimensional Conformal Radiation Therapy

Intervention Type: RADIATION

Patients undergo radiation therapy once daily for approximately 3 weeks

Erlotinib Hydrochloride

Intervention Type: DRUG

Given orally

Stereotactic Radiosurgery

Intervention Type: RADIATION

Patients undergo surgery after radiation therapy

Interventions

3-Dimensional Conformal Radiation Therapy

Patients undergo radiation therapy once daily for approximately 3 weeks

Intervention Type: RADIATION

Erlotinib Hydrochloride

Given orally

Intervention Type: DRUG

Stereotactic Radiosurgery

Patients undergo surgery after radiation therapy

Intervention Type: RADIATION

Temozolomide

Given orally

Intervention Type: DRUG

Other Intervention Names

3-dimensional radiation therapy; 3D CONFORMAL RADIATION THERAPY; 3D CRT; 3D-CRT; Conformal Therapy; Radiation Conformal Therapy; Cp-358,774; OSI-774; Tarceva; Stereotactic External Beam Irradiation; stereotactic external-beam radiation therapy; stereotactic radiation therapy; Stereotactic Radiotherapy; stereotaxic radiation therapy; stereotaxic radiosurgery; 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

Eligibility 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 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
• 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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Radiation Therapy Oncology Group

NETWORK

Sponsor Role: collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Paul Sperduto

Role: PRINCIPAL_INVESTIGATOR

Radiation Therapy Oncology Group

Locations

Arizona Oncology Services Foundation

Scottsdale, Arizona, United States

Scottsdale Health Care-Osborn

Scottsdale, Arizona, United States

Providence Saint Joseph Medical Center/Disney Family Cancer Center

Burbank, California, United States

Kaiser Permanente Los Angeles Medical Center

Los Angeles, California, United States

Pomona Valley Hospital Medical Center

Pomona, California, United States

Saint Mary's Hospital and Regional Medical Center

Grand Junction, Colorado, United States

Christiana Care Health System-Christiana Hospital

Newark, Delaware, United States

Baptist MD Anderson Cancer Center

Jacksonville, Florida, United States

Integrated Community Oncology Network-Southside Cancer Center

Jacksonville, Florida, United States

Baptist Medical Center South

Jacksonville, Florida, United States

Integrated Community Oncology Network-Florida Cancer Center Beaches

Jacksonville Beach, Florida, United States

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, United States

21st Century Oncology-Orange Park

Orange Park, Florida, United States

UF Cancer Center at Orlando Health

Orlando, Florida, United States

21st Century Oncology-Palatka

Palatka, Florida, United States

Bay Medical Center

Panama City, Florida, United States

Integrated Community Oncology Network-Flager Cancer Center

Saint Augustine, Florida, United States

Tallahassee Memorial HealthCare

Tallahassee, Florida, United States

John B Amos Cancer Center

Columbus, Georgia, United States

Saint Alphonsus Cancer Care Center-Boise

Boise, Idaho, United States

Northwest Community Hospital

Arlington Heights, Illinois, United States

Northwestern University

Chicago, Illinois, United States

Ingalls Memorial Hospital

Harvey, Illinois, United States

Saint John's Hospital

Springfield, Illinois, United States

Parkview Hospital Randallia

Fort Wayne, Indiana, United States

Franciscan Saint Margaret Health-Hammond Campus

Hammond, Indiana, United States

IU Health Methodist Hospital

Indianapolis, Indiana, United States

Finley Hospital

Dubuque, Iowa, United States

Norton Suburban Hospital and Medical Campus

Louisville, Kentucky, United States

University of Maryland/Greenebaum Cancer Center

Baltimore, Maryland, United States

Saint Agnes Hospital

Baltimore, Maryland, United States

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, United States

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, United States

West Michigan Cancer Center

Kalamazoo, Michigan, United States

Fairview Ridges Hospital

Burnsville, Minnesota, United States

Mercy Hospital

Coon Rapids, Minnesota, United States

Fairview-Southdale Hospital

Edina, Minnesota, United States

Unity Hospital

Fridley, Minnesota, United States

Abbott-Northwestern Hospital

Minneapolis, Minnesota, United States

University of Minnesota/Masonic Cancer Center

Minneapolis, Minnesota, United States

North Memorial Medical Health Center

Robbinsdale, Minnesota, United States

Coborn Cancer Center at Saint Cloud Hospital

Saint Cloud, Minnesota, United States

Saint Cloud Hospital

Saint Cloud, Minnesota, United States

Metro Minnesota Community Oncology Research Consortium

Saint Louis Park, Minnesota, United States

Park Nicollet Clinic - Saint Louis Park

Saint Louis Park, Minnesota, United States

United Hospital

Saint Paul, Minnesota, United States

Ridgeview Medical Center

Waconia, Minnesota, United States

Saint Louis University Hospital

St Louis, Missouri, United States

Nevada Cancer Research Foundation CCOP

Las Vegas, Nevada, United States

Renown Regional Medical Center

Reno, Nevada, United States

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

New Brunswick, New Jersey, United States

Riverview Medical Center/Booker Cancer Center

Red Bank, New Jersey, United States

Sparta Cancer Treatment Center

Sparta, New Jersey, United States

University of Rochester

Rochester, New York, United States

Mission Hospital-Memorial Campus

Asheville, North Carolina, United States

Summa Akron City Hospital/Cooper Cancer Center

Akron, Ohio, United States

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Natalie Warren Bryant Cancer Center at Saint Francis

Tulsa, Oklahoma, United States

Delaware County Memorial Hospital

Drexel Hill, Pennsylvania, United States

Radiation Therapy Oncology Group

Philadelphia, Pennsylvania, United States

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, United States

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Reading Hospital

West Reading, Pennsylvania, United States

Medical University of South Carolina

Charleston, South Carolina, United States

Thompson Cancer Survival Center

Knoxville, Tennessee, United States

Arlington Cancer Center

Arlington, Texas, United States

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, United States

University of Texas Medical Branch

Galveston, Texas, United States

M D Anderson Cancer Center

Houston, Texas, United States

Intermountain Medical Center

Murray, Utah, United States

McKay-Dee Hospital Center

Ogden, Utah, United States

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, United States

LDS Hospital

Salt Lake City, Utah, United States

Sentara Norfolk General Hospital

Norfolk, Virginia, United States

Virginia Commonwealth University/Massey Cancer Center

Richmond, Virginia, United States

Virginia Mason Medical Center

Seattle, Washington, United States

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, United States

Froedtert and the Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Wheaton Franciscan Cancer Care - All Saints

Racine, Wisconsin, United States

CancerCare Manitoba

Winnipeg, Manitoba, Canada

Ottawa Hospital-Civic Campus

Ottawa, Ontario, Canada

McGill University Department of Oncology

Montreal, Quebec, Canada

Countries

United States; Canada

Other Identifiers

NCI-2009-00720

Identifier Type: REGISTRY

Identifier Source: secondary_id

CDR0000389490

Identifier Type: -

Identifier Source: secondary_id

RTOG 0320

Identifier Type: -

Identifier Source: secondary_id

RTOG 0320

Identifier Type: OTHER

Identifier Source: secondary_id

RTOG-0320

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA021661

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2009-00720

Identifier Type: -

Identifier Source: org_study_id