Erlotinib and Temozolomide With Radiation Therapy in Treating Patients With Glioblastoma Multiforme or Other Brain Tumors
- Conditions
- Adult Giant Cell GlioblastomaAdult GlioblastomaAdult Gliosarcoma
- Interventions
- Registration Number
- NCT00039494
- Lead Sponsor
- National Cancer Institute (NCI)
- Brief Summary
This pilot phase II trial is studying the side effects and best dose of erlotinib when given with temozolomide and radiation therapy and to see how well they work in treating patients with glioblastoma multiforme or other brain tumors. Radiation therapy uses high-energy x-rays to damage tumor cells. Erlotinib may interfere with the growth of tumor cells, slow the growth of the tumor, and make the tumor cells more sensitive to radiation therapy. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining erlotinib and temozolomide with radiation therapy may kill more tumor cells.
- Detailed Description
PILOT STUDY OBJECTIVES:
I. Determine the maximum tolerated dose of erlotinib administered with temozolomide and radiotherapy in patients with glioblastoma multiforme or other grade 4 brain tumors who are currently on enzyme-inducing anticonvulsant (EIAC) therapy vs no EIAC therapy.
II. Determine the safety and tolerability of this regimen in these patients. III. Determine the toxic effects of this regimen in these patients. IV. Determine the efficacy of this regimen, in terms of 1-year survival, in these patients.
PHASE II OBJECTIVES:
I. Determine the response rate and time to progression in patients treated with this regimen.
II. Determine the 6-month progression-free survival of patients treated with this regimen.
III. Determine the toxic effects of this regimen in these patients.
OUTLINE: This is a multicenter, dose-escalation pilot study of erlotinib followed by a phase II study. Patients are stratified according to concurrent enzyme-inducing anticonvulsant drug use (yes vs no).
PILOT STUDY: Patients receive oral erlotinib once daily. After 1 week of erlotinib alone, patients also receive oral temozolomide once daily for 6 weeks and undergo concurrent radiotherapy 5 days a week for 6 weeks. After completion of radiotherapy, patients continue to receive erlotinib once daily alone in the absence of disease progression or unacceptable toxicity. Beginning 4 weeks after the completion of radiotherapy, patients also receive oral temozolomide once daily for 5 days. Temozolomide treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
PHASE II: Once the MTD of erlotinib is determined, additional patients are treated with erlotinib at the MTD, temozolomide, and radiotherapy as above.
Patients are followed every 3 months for 5 years and then annually for 10 years.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 171
-
Histologically confirmed diagnosis of 1 of the following:
- Glioblastoma multiforme (grade 4 astrocytoma)
- Gliosarcomas
- Other grade 4 astrocytoma variants (e.g., giant cell)
-
Must be enrolled at least 1 week, but no more than 4 weeks, after prior biopsy or surgery
-
Performance status - ECOG 0-2
-
Performance status - Karnofsky 60-100%
-
At least 6 months
-
Absolute neutrophil count at least 1,500/mm^3
-
Platelet count at least 100,000/mm^3
-
Hemoglobin ≥ 9 g/dL
-
Total bilirubin ≤ upper limit of normal (ULN)
-
AST no greater than 2.5 times ULN
-
Creatinine no greater than 1.5 times ULN
-
No symptomatic congestive heart failure
-
No unstable angina pectoris
-
No cardiac arrhythmia
-
No inability to take oral medications
-
No requirement for IV alimentation
-
No active uncontrolled peptic ulcer disease
-
No abnormalities of the cornea (e.g., dry eye syndrome or Sjögren's syndrome)
-
No congenital abnormality (e.g., Fuch's dystrophy)
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No abnormal slit-lamp examination using a vital dye (e.g., fluorescein or Bengal-Rose)
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No abnormal corneal sensitivity test (e.g., Schirmer test or similar tear production test)
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No prior allergy or intolerance to dacarbazine
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No other active malignancy requiring treatment
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No other concurrent uncontrolled illness
-
No ongoing or active infection
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No psychiatric illness or social situation that would preclude study compliance
-
Not pregnant or nursing
-
Negative pregnancy test
-
Fertile patients must use effective contraception
-
No prior chemotherapy for any brain tumor
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No prior temozolomide
-
No prior radiotherapy for any brain tumor
-
No other concurrent investigational agents
-
More than 21 days since prior major surgery (excluding neurosurgical biopsy or brain tumor resection)
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No prior surgical procedures affecting absorption
-
No concurrent combination antiretroviral therapy for HIV-positive patients
-
No concurrent warfarin
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Treatment (erlotinib hydrochloride, radiation, temozolomide) erlotinib hydrochloride Patients receive oral erlotinib once daily. After 1 week of erlotinib alone, patients also receive oral temozolomide once daily for 6 weeks and undergo concurrent radiotherapy 5 days a week for 6 weeks. After completion of radiotherapy, patients continue to receive erlotinib once daily alone in the absence of disease progression or unacceptable toxicity. Beginning 4 weeks after the completion of radiotherapy, patients also receive oral temozolomide once daily for 5 days. Temozolomide treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Treatment (erlotinib hydrochloride, radiation, temozolomide) 3-dimensional conformal radiation therapy Patients receive oral erlotinib once daily. After 1 week of erlotinib alone, patients also receive oral temozolomide once daily for 6 weeks and undergo concurrent radiotherapy 5 days a week for 6 weeks. After completion of radiotherapy, patients continue to receive erlotinib once daily alone in the absence of disease progression or unacceptable toxicity. Beginning 4 weeks after the completion of radiotherapy, patients also receive oral temozolomide once daily for 5 days. Temozolomide treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Treatment (erlotinib hydrochloride, radiation, temozolomide) temozolomide Patients receive oral erlotinib once daily. After 1 week of erlotinib alone, patients also receive oral temozolomide once daily for 6 weeks and undergo concurrent radiotherapy 5 days a week for 6 weeks. After completion of radiotherapy, patients continue to receive erlotinib once daily alone in the absence of disease progression or unacceptable toxicity. Beginning 4 weeks after the completion of radiotherapy, patients also receive oral temozolomide once daily for 5 days. Temozolomide treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
- Primary Outcome Measures
Name Time Method Survival At 52 weeks Overall survival distribution From start of study therapy to death due to any cause, up to 15 years The overall survival distribution will be estimated using the method of Kaplan-Meier. The success probability, i.e., 12-month survival percentage, will be estimated as the number of evaluable patients still alive at 366 days divided by the total number of evaluable patients followed for at least 366 days.
- Secondary Outcome Measures
Name Time Method Time-to-disease progression From start of study therapy to documentation of disease progression, up to 15 years The time-to-progression distribution will be estimated using the Kaplan-Meier method.
Maximum toxicity grade, assessed by Common Terminology Criteria for Adverse Events (CTCAE) Up to 15 years Frequency tables will be reviewed to determine toxicity patterns.
Trial Locations
- Locations (139)
Graham Hospital Association
🇺🇸Canton, Illinois, United States
Mcdonough District Hospital
🇺🇸Macomb, Illinois, United States
Siouxland Regional Cancer Center
🇺🇸Sioux City, Iowa, United States
Siouxland Hematology Oncology Associates
🇺🇸Sioux City, Iowa, United States
Mercy Medical Center-Sioux City
🇺🇸Sioux City, Iowa, United States
Saint Luke's Regional Medical Center
🇺🇸Sioux City, Iowa, United States
Saint Joseph's Hospital - Healtheast
🇺🇸Saint Paul, Minnesota, United States
Genesys Regional Medical Center-West Flint Campus
🇺🇸Flint, Michigan, United States
Meeker County Memorial Hospital
🇺🇸Litchfield, Minnesota, United States
Saint Cloud Hospital
🇺🇸Saint Cloud, Minnesota, United States
Woodwinds Health Campus
🇺🇸Woodbury, Minnesota, United States
Glacier Oncology PLLC
🇺🇸Kalispell, Montana, United States
Saint Elizabeth Regional Medical Center
🇺🇸Lincoln, Nebraska, United States
Bryan LGH Medical Center West
🇺🇸Lincoln, Nebraska, United States
Hematology-Oncology Centers of the Northern Rockies PC
🇺🇸Billings, Montana, United States
Montana Cancer Specialists
🇺🇸Missoula, Montana, United States
Welch Cancer Center
🇺🇸Sheridan, Wyoming, United States
Cancer Center of Kansas-Independence
🇺🇸Independence, Kansas, United States
Cancer Center of Kansas - Salina
🇺🇸Salina, Kansas, United States
Cancer Center of Kansas - Winfield
🇺🇸Winfield, Kansas, United States
Cancer Center of Kansas-Wichita Medical Arts Tower
🇺🇸Wichita, Kansas, United States
Cancer Center of Kansas - Main Office
🇺🇸Wichita, Kansas, United States
Via Christi Regional Medical Center
🇺🇸Wichita, Kansas, United States
Wesley Medical Center
🇺🇸Wichita, Kansas, United States
Virginia Piper Cancer Institute
🇺🇸Minneapolis, Minnesota, United States
Cancer Center of Kansas - Pratt
🇺🇸Pratt, Kansas, United States
OSF Saint Francis Medical Center
🇺🇸Peoria, Illinois, United States
Saint Anthony Memorial Health Center
🇺🇸Michigan City, Indiana, United States
Mayo Clinic in Florida
🇺🇸Jacksonville, Florida, United States
Saint John Macomb-Oakland Hospital
🇺🇸Warren, Michigan, United States
Carle Clinic-Urbana Main
🇺🇸Urbana, Illinois, United States
Illinois Oncology Research Association CCOP
🇺🇸Peoria, Illinois, United States
Illinois CancerCare-Ottawa Clinic
🇺🇸Ottawa, Illinois, United States
Valley Cancer Center
🇺🇸Spring Valley, Illinois, United States
Rush - Copley Medical Center
🇺🇸Aurora, Illinois, United States
Illinois Valley Hospital
🇺🇸Peru, Illinois, United States
Saint Anthony Memorial Hospital
🇺🇸Effingham, Illinois, United States
Constantinou, Costas L MD (UIA Investigator)
🇺🇸Bettendorf, Iowa, United States
Cancer Center of Kansas - Fort Scott
🇺🇸Fort Scott, Kansas, United States
Mayo Clinic in Arizona
🇺🇸Scottsdale, Arizona, United States
Saint Joseph Medical Center
🇺🇸Bloomington, Illinois, United States
Stoffel, Thomas J MD (UIA Investigator)
🇺🇸Moline, Illinois, United States
Perry Memorial Hospital
🇺🇸Princeton, Illinois, United States
Sparrow Hospital
🇺🇸Lansing, Michigan, United States
Associates In Womens Health
🇺🇸Wichita, Kansas, United States
Saint Margaret's Hospital
🇺🇸Spring Valley, Illinois, United States
Saint Anthony Regional Hospital
🇺🇸Carroll, Iowa, United States
Cancer Center of Kansas - Dodge City
🇺🇸Dodge City, Kansas, United States
Cancer Center of Kansas - El Dorado
🇺🇸El Dorado, Kansas, United States
Hurley Medical Center
🇺🇸Flint, Michigan, United States
Wichita CCOP
🇺🇸Wichita, Kansas, United States
McFarland Clinic
🇺🇸Ames, Iowa, United States
Oakwood Hospital
🇺🇸Dearborn, Michigan, United States
Hospital District Sixth of Harper County
🇺🇸Anthony, Kansas, United States
Cancer Center of Kansas - Chanute
🇺🇸Chanute, Kansas, United States
Cancer Center of Kansas-Kingman
🇺🇸Kingman, Kansas, United States
Lawrence Memorial Hospital
🇺🇸Lawrence, Kansas, United States
Cancer Center of Kansas - Newton
🇺🇸Newton, Kansas, United States
Etzell, Paul S MD (UIA Investigator)
🇺🇸Fergus Falls, Minnesota, United States
Medini, Eitan MD (UIA Investigator)
🇺🇸Alexandria, Minnesota, United States
Allegiance Health
🇺🇸Jackson, Michigan, United States
Essentia Health Saint Mary's Medical Center
🇺🇸Duluth, Minnesota, United States
Mid Dakota Clinic
🇺🇸Bismarck, North Dakota, United States
Saint Mary's of Michigan
🇺🇸Saginaw, Michigan, United States
Saint Luke's Hospital
🇺🇸Cedar Rapids, Iowa, United States
Burgess Memorial Hospital
🇺🇸Onawa, Iowa, United States
Oncology Associates at Mercy Medical Center
🇺🇸Cedar Rapids, Iowa, United States
Sharis, Christine M MD (UIA Investigator)
🇺🇸Moline, Illinois, United States
Medical Oncology and Hematology Associates-West Des Moines
🇺🇸Clive, Iowa, United States
Mobile Infirmary Medical Center
🇺🇸Mobile, Alabama, United States
Northeast Georgia Cancer Care LLC
🇺🇸Athens, Georgia, United States
Memorial Hospital
🇺🇸Carthage, Illinois, United States
Eureka Hospital
🇺🇸Eureka, Illinois, United States
Galesburg Cottage Hospital
🇺🇸Galesburg, Illinois, United States
Western Illinois Cancer Treatment Center
🇺🇸Galesburg, Illinois, United States
Illinois CancerCare Galesburg
🇺🇸Galesburg, Illinois, United States
Kewanee Hospital
🇺🇸Kewanee, Illinois, United States
Mason District Hospital
🇺🇸Havana, Illinois, United States
Hopedale Medical Complex - Hospital
🇺🇸Hopedale, Illinois, United States
Joliet Oncology-Hematology Associates Limited
🇺🇸Joliet, Illinois, United States
Garneau, Stewart C MD (UIA Investigator)
🇺🇸Moline, Illinois, United States
Porubcin, Michael MD (UIA Investigator)
🇺🇸Moline, Illinois, United States
Vigliotti, Antonio, P.G. M.D. (UIA Investigator)
🇺🇸Moline, Illinois, United States
Bromenn Regional Medical Center
🇺🇸Normal, Illinois, United States
Community Cancer Center Foundation
🇺🇸Normal, Illinois, United States
Ottawa Regional Hospital and Healthcare Center
🇺🇸Ottawa, Illinois, United States
Pekin Cancer Treatment Center
🇺🇸Pekin, Illinois, United States
Pekin Hospital
🇺🇸Pekin, Illinois, United States
Methodist Medical Center of Illinois
🇺🇸Peoria, Illinois, United States
Proctor Hospital
🇺🇸Peoria, Illinois, United States
Illinois CancerCare-Peoria
🇺🇸Peoria, Illinois, United States
Cedar Rapids Oncology Association
🇺🇸Cedar Rapids, Iowa, United States
Alegent Health Mercy Hospital
🇺🇸Council Bluffs, Iowa, United States
Mercy Hospital
🇺🇸Cedar Rapids, Iowa, United States
Community Memorial Hospital
🇺🇸Missouri Valley, Iowa, United States
Essentia Health Saint Joseph's Medical Center
🇺🇸Brainerd, Minnesota, United States
Harris, John Gilbert MD (UIA Investigator)
🇺🇸Alexandria, Minnesota, United States
Brainerd Medical Center Inc
🇺🇸Brainerd, Minnesota, United States
Essentia Health Duluth Clinic CCOP
🇺🇸Duluth, Minnesota, United States
Miller-Dwan Hospital
🇺🇸Duluth, Minnesota, United States
Sanford Clinic North-Bemidgi
🇺🇸Bemidji, Minnesota, United States
Swenson, Wade II, MD (UIA Investigator)
🇺🇸Fergus Falls, Minnesota, United States
CentraCare Clinic
🇺🇸Saint Cloud, Minnesota, United States
Chippewa County - Montevideo Hospital
🇺🇸Montevideo, Minnesota, United States
Montana Cancer Consortium CCOP
🇺🇸Billings, Montana, United States
Northern Rockies Radiation Oncology Center
🇺🇸Billings, Montana, United States
Adult and Pediatric Urology PLLP
🇺🇸Sartell, Minnesota, United States
Bozeman Deaconess Cancer Center
🇺🇸Bozeman, Montana, United States
Saint Vincent Healthcare
🇺🇸Billings, Montana, United States
Deaconess Medical Center
🇺🇸Billings, Montana, United States
Billings Clinic
🇺🇸Billings, Montana, United States
Internal Medicine of Bozeman
🇺🇸Bozeman, Montana, United States
Saint Peter's Community Hospital
🇺🇸Helena, Montana, United States
Bozeman Deaconess Hospital
🇺🇸Bozeman, Montana, United States
Saint James Community Hospital and Cancer Treatment Center
🇺🇸Butte, Montana, United States
Fremont Area Medical Center
🇺🇸Fremont, Nebraska, United States
Community Medical Hospital
🇺🇸Missoula, Montana, United States
Saint Patrick Hospital - Community Hospital
🇺🇸Missoula, Montana, United States
Midlands Community Hospital
🇺🇸Papillion, Nebraska, United States
Bryan LGH Medical Center East
🇺🇸Lincoln, Nebraska, United States
Saint Alexius Medical Center
🇺🇸Bismarck, North Dakota, United States
Bismarck Cancer Center
🇺🇸Bismarck, North Dakota, United States
University of Virginia
🇺🇸Charlottesville, Virginia, United States
Sanford Bismarck Medical Center
🇺🇸Bismarck, North Dakota, United States
Sanford Clinic North-Fargo
🇺🇸Fargo, North Dakota, United States
Sanford Medical Center-Fargo
🇺🇸Fargo, North Dakota, United States
Mercy Capitol
🇺🇸Des Moines, Iowa, United States
Iowa Methodist Medical Center
🇺🇸Des Moines, Iowa, United States
Iowa Oncology Research Association CCOP
🇺🇸Des Moines, Iowa, United States
Medical Oncology and Hematology Associates-Des Moines
🇺🇸Des Moines, Iowa, United States
Medical Oncology and Hematology Associates
🇺🇸Des Moines, Iowa, United States
Mercy Medical Center - Des Moines
🇺🇸Des Moines, Iowa, United States
Iowa Lutheran Hospital
🇺🇸Des Moines, Iowa, United States
Saint Joseph Mercy Hospital
🇺🇸Ann Arbor, Michigan, United States
Michigan Cancer Research Consortium Community Clinical Oncology Program
🇺🇸Ann Arbor, Michigan, United States
Saint John Hospital and Medical Center
🇺🇸Detroit, Michigan, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Cancer Center of Kansas - Parsons
🇺🇸Parsons, Kansas, United States
Cancer Center of Kansas - Wellington
🇺🇸Wellington, Kansas, United States