Know Cancer

or
forgot password

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


Phase 3
18 Years
N/A
Not Enrolling
Both
Recurrent Non-small Cell Lung Cancer, Stage IV Non-small Cell Lung Cancer, Tumors Metastatic to Brain

Thank you

Trial Information

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


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.


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)

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Overall Survival

Outcome Description:

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.

Outcome Time Frame:

From randomizaton to date of death for last follow-up. Analysis occurs after all patients have been potentiall followed for 9 months.

Safety Issue:

No

Principal Investigator

Paul Sperduto

Investigator Role:

Principal Investigator

Investigator Affiliation:

American College of Radiology Imaging Network

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2009-00720

NCT ID:

NCT00096265

Start Date:

October 2004

Completion Date:

Related Keywords:

  • Recurrent Non-Small Cell Lung Cancer
  • Stage IV Non-Small Cell Lung Cancer
  • Tumors Metastatic to Brain
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms
  • Neoplasm Metastasis

Name

Location

Akron City HospitalAkron, Ohio  44304
Cleveland Clinic FoundationCleveland, Ohio  44195
Fox Chase Cancer CenterPhiladelphia, Pennsylvania  19111
West Michigan Cancer CenterKalamazoo, Michigan  49007-3731
Fairview Ridges HospitalBurnsville, Minnesota  55337
United HospitalSt. Paul, Minnesota  55102
Ridgeview Medical CenterWaconia, Minnesota  55387
Massachusetts General Hospital Cancer CenterBoston, Massachusetts  02114
Northwest Community HospitalArlington Heights, Illinois  60005
Delaware County Memorial HospitalDrexel Hill, Pennsylvania  19026
LDS HospitalSalt Lake City, Utah  84143
Tallahassee Memorial HealthcareTallahassee, Florida  32308
University of Wisconsin Hospital and ClinicsMadison, Wisconsin  53792-0001
Thompson Cancer Survival CenterKnoxville, Tennessee  37916
McKay-Dee Hospital CenterOgden, Utah  84403
Mercy HospitalCoon Rapids, Minnesota  55433
Fairview-Southdale HospitalEdina, Minnesota  55435
Abbott-Northwestern HospitalMinneapolis, Minnesota  55407
Pomona Valley Hospital Medical CenterPomona, California  91767
Northwestern UniversityChicago, Illinois  60611
Saint Louis University HospitalSt. Louis, Missouri  63110-0250
University of RochesterRochester, New York  14642
Wayne State UniversityDetroit, Michigan  48202
University of Texas Southwestern Medical CenterDallas, Texas  
Virginia Mason CCOPSeattle, Washington  98101
Huntsman Cancer Institute/University of UtahSalt Lake City, Utah  84112
Metro-Minnesota CCOPSt. Louis Park, Minnesota  
Thomas Jefferson University HospitalPhiladelphia, Pennsylvania  19131
Providence Saint Joseph Medical CenterBurbank, California  91505-4866
Saint Mary's Hospital and Regional Medical CenterGrand Junction, Colorado  81502
Edna Williams Cancer Center at the Baptist Cancer InstituteJacksonville, Florida  32207
M D Anderson Cancer Center- OrlandoOrlando, Florida  32806
John B Amos Cancer CenterColumbus, Georgia  31904
Unity HospitalFridley, Minnesota  55432
North Memorial Medical Health CenterRobbinsdale, Minnesota  55422
Park Nicollet Clinic - Saint Louis ParkSaint Louis Park, Minnesota  55416
Nevada Cancer Research Foundation CCOPLas Vegas, Nevada  89106
Sparta Cancer Treatment CenterSparta, New Jersey  07871
Mission Hospitals IncAsheville, North Carolina  28801
University of Maryland Greenebaum Cancer CenterBaltimore, Maryland  21201
Intermountain Medical CenterMurray, Utah  84157
University of Minnesota Medical Center-FairviewMinneapolis, Minnesota  55455
UMDNJ - Robert Wood Johnson University HospitalNew Brunswick, New Jersey  08903
Christiana Care Health System-Christiana HospitalNewark, Delaware  19718
Riverview Medical Center/Booker Cancer CenterRed Bank, New Jersey  07701
Cancer Specialists of North Florida-SouthsideJacksonville, Florida  32207
Cancer Specialists of North Florida-BeachesJacksonville Beach, Florida  32250
Cancer Specialists of North Florida-Baptist SouthJascksonville, Florida  32258
Cancer Specialists of North Florida-Orange ParkOrange Park, Florida  32073
Cancer Specialists of North Florida-PutnamPalatka, Florida  32177
Cancer Specialists of North Florida-Saint AugustineSaint Augustine, Florida  32086
Saint Margaret Mercy Healthcare Centers- North CampusHammond, Indiana  46320
IU Health Methodist HospitalIndianapolis, Indiana  46202
Sentara HospitalsNorfolk, Virginia  23507