Erlotinib and Temozolomide With Radiation Therapy in Treating Patients With Glioblastoma Multiforme or Other Brain Tumors

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00039494
First received: June 6, 2002
Last updated: August 1, 2013
Last verified: August 2013
  Purpose

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.


Condition Intervention Phase
Adult Giant Cell Glioblastoma
Adult Glioblastoma
Adult Gliosarcoma
Drug: erlotinib hydrochloride
Radiation: 3-dimensional conformal radiation therapy
Drug: temozolomide
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot and Phase II Study of OSI-774 and Temozolomide in Combination With Radiation Therapy in Glioblastoma Multiforme

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Survival [ Time Frame: At 52 weeks ] [ Designated as safety issue: No ]
  • Overall survival distribution [ Time Frame: From start of study therapy to death due to any cause, up to 15 years ] [ Designated as safety issue: No ]
    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:
  • Time-to-disease progression [ Time Frame: From start of study therapy to documentation of disease progression, up to 15 years ] [ Designated as safety issue: No ]
    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) [ Time Frame: Up to 15 years ] [ Designated as safety issue: Yes ]
    Frequency tables will be reviewed to determine toxicity patterns.


Estimated Enrollment: 171
Study Start Date: December 2002
Primary Completion Date: July 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (erlotinib hydrochloride, radiation, 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.
Drug: erlotinib hydrochloride
Given orally
Other Names:
  • CP-358,774
  • erlotinib
  • OSI-774
Radiation: 3-dimensional conformal radiation therapy
Other Names:
  • 3D conformal radiation therapy
  • 3D-CRT
Drug: temozolomide
Given orally
Other Names:
  • SCH 52365
  • Temodal
  • Temodar
  • TMZ

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.

  Eligibility

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

Inclusion Criteria:

  • 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)
  • No abnormal slit-lamp examination using a vital dye (e.g., fluorescein or Bengal-Rose)
  • No abnormal corneal sensitivity test (e.g., Schirmer test or similar tear production test)
  • No prior allergy or intolerance to dacarbazine
  • No other active malignancy requiring treatment
  • No other concurrent uncontrolled illness
  • No ongoing or active infection
  • 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
  • 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)
  • No prior surgical procedures affecting absorption
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No concurrent warfarin
  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: NCT00039494

  Hide Study Locations
Locations
United States, Alabama
Mobile Infirmary Medical Center
Mobile, Alabama, United States, 36607
United States, Arizona
Mayo Clinic in Arizona
Scottsdale, Arizona, United States, 85259
United States, Florida
Mayo Clinic in Florida
Jacksonville, Florida, United States, 32224-9980
United States, Georgia
Northeast Georgia Cancer Care LLC
Athens, Georgia, United States, 30607
United States, Illinois
Rush - Copley Medical Center
Aurora, Illinois, United States, 60504
Saint Joseph Medical Center
Bloomington, Illinois, United States, 61701
Graham Hospital Association
Canton, Illinois, United States, 61520
Memorial Hospital
Carthage, Illinois, United States, 62321
Saint Anthony Memorial Hospital
Effingham, Illinois, United States, 62401
Eureka Hospital
Eureka, Illinois, United States, 61530
Western Illinois Cancer Treatment Center
Galesburg, Illinois, United States, 61401
Galesburg Cottage Hospital
Galesburg, Illinois, United States, 61401
Illinois CancerCare Galesburg
Galesburg, Illinois, United States, 61401
Mason District Hospital
Havana, Illinois, United States, 62644
Hopedale Medical Complex - Hospital
Hopedale, Illinois, United States, 61747
Joliet Oncology-Hematology Associates Limited
Joliet, Illinois, United States, 60435
Kewanee Hospital
Kewanee, Illinois, United States, 61443
Mcdonough District Hospital
Macomb, Illinois, United States, 61455
Garneau, Stewart C MD (UIA Investigator)
Moline, Illinois, United States, 61265
Stoffel, Thomas J MD (UIA Investigator)
Moline, Illinois, United States, 61265
Porubcin, Michael MD (UIA Investigator)
Moline, Illinois, United States, 61265
Sharis, Christine M MD (UIA Investigator)
Moline, Illinois, United States, 61265
Vigliotti, Antonio, P.G. M.D. (UIA Investigator)
Moline, Illinois, United States, 61265
Bromenn Regional Medical Center
Normal, Illinois, United States, 61761
Community Cancer Center Foundation
Normal, Illinois, United States, 61761
Ottawa Regional Hospital and Healthcare Center
Ottawa, Illinois, United States, 61350
Illinois CancerCare-Ottawa Clinic
Ottawa, Illinois, United States, 61350
Pekin Cancer Treatment Center
Pekin, Illinois, United States, 61554
Pekin Hospital
Pekin, Illinois, United States, 61554
Illinois Oncology Research Association CCOP
Peoria, Illinois, United States, 61615
Illinois CancerCare-Peoria
Peoria, Illinois, United States, 61615
Methodist Medical Center of Illinois
Peoria, Illinois, United States, 61603
OSF Saint Francis Medical Center
Peoria, Illinois, United States, 61637
Proctor Hospital
Peoria, Illinois, United States, 61614
Illinois Valley Hospital
Peru, Illinois, United States, 61354
Perry Memorial Hospital
Princeton, Illinois, United States, 61356
Valley Cancer Center
Spring Valley, Illinois, United States, 61362
Saint Margaret's Hospital
Spring Valley, Illinois, United States, 61362
Carle Clinic-Urbana Main
Urbana, Illinois, United States, 61801
United States, Indiana
Saint Anthony Memorial Health Center
Michigan City, Indiana, United States, 46360
United States, Iowa
McFarland Clinic
Ames, Iowa, United States, 50010
Constantinou, Costas L MD (UIA Investigator)
Bettendorf, Iowa, United States, 52722
Saint Anthony Regional Hospital
Carroll, Iowa, United States, 51401
Cedar Rapids Oncology Association
Cedar Rapids, Iowa, United States, 52403
Oncology Associates at Mercy Medical Center
Cedar Rapids, Iowa, United States, 52403
Mercy Hospital
Cedar Rapids, Iowa, United States, 52403
Saint Luke's Hospital
Cedar Rapids, Iowa, United States, 52402
Medical Oncology and Hematology Associates-West Des Moines
Clive, Iowa, United States, 50325
Alegent Health Mercy Hospital
Council Bluffs, Iowa, United States, 51503
Medical Oncology and Hematology Associates-Des Moines
Des Moines, Iowa, United States, 50309
Mercy Medical Center - Des Moines
Des Moines, Iowa, United States, 50314
Medical Oncology and Hematology Associates
Des Moines, Iowa, United States, 50314
Mercy Capitol
Des Moines, Iowa, United States, 50307
Iowa Methodist Medical Center
Des Moines, Iowa, United States, 50309
Iowa Oncology Research Association CCOP
Des Moines, Iowa, United States, 50309
Iowa Lutheran Hospital
Des Moines, Iowa, United States, 50316
Community Memorial Hospital
Missouri Valley, Iowa, United States, 51555
Burgess Memorial Hospital
Onawa, Iowa, United States, 51040
Saint Luke's Regional Medical Center
Sioux City, Iowa, United States, 51104
Siouxland Regional Cancer Center
Sioux City, Iowa, United States, 51101-1733
Siouxland Hematology Oncology Associates
Sioux City, Iowa, United States, 51101
Mercy Medical Center-Sioux City
Sioux City, Iowa, United States, 51104
United States, Kansas
Hospital District Sixth of Harper County
Anthony, Kansas, United States, 67003
Cancer Center of Kansas - Chanute
Chanute, Kansas, United States, 66720
Cancer Center of Kansas - Dodge City
Dodge City, Kansas, United States, 67801
Cancer Center of Kansas - El Dorado
El Dorado, Kansas, United States, 67042
Cancer Center of Kansas - Fort Scott
Fort Scott, Kansas, United States, 66701
Cancer Center of Kansas-Independence
Independence, Kansas, United States, 67301
Cancer Center of Kansas-Kingman
Kingman, Kansas, United States, 67068
Lawrence Memorial Hospital
Lawrence, Kansas, United States, 66044
Cancer Center of Kansas - Newton
Newton, Kansas, United States, 67114
Cancer Center of Kansas - Parsons
Parsons, Kansas, United States, 67357
Cancer Center of Kansas - Pratt
Pratt, Kansas, United States, 67124
Cancer Center of Kansas - Salina
Salina, Kansas, United States, 67401
Cancer Center of Kansas - Wellington
Wellington, Kansas, United States, 67152
Cancer Center of Kansas - Main Office
Wichita, Kansas, United States, 67214
Cancer Center of Kansas-Wichita Medical Arts Tower
Wichita, Kansas, United States, 67208
Wichita CCOP
Wichita, Kansas, United States, 67214
Associates In Womens Health
Wichita, Kansas, United States, 67208
Via Christi Regional Medical Center
Wichita, Kansas, United States, 67214
Wesley Medical Center
Wichita, Kansas, United States, 67214
Cancer Center of Kansas - Winfield
Winfield, Kansas, United States, 67156
United States, Michigan
Saint Joseph Mercy Hospital
Ann Arbor, Michigan, United States, 48106-0995
Michigan Cancer Research Consortium Community Clinical Oncology Program
Ann Arbor, Michigan, United States, 48106
Oakwood Hospital
Dearborn, Michigan, United States, 48124
Saint John Hospital and Medical Center
Detroit, Michigan, United States, 48236
Genesys Regional Medical Center-West Flint Campus
Flint, Michigan, United States, 48532
Hurley Medical Center
Flint, Michigan, United States, 48502
Allegiance Health
Jackson, Michigan, United States, 49201
Sparrow Hospital
Lansing, Michigan, United States, 48912
Saint Mary's of Michigan
Saginaw, Michigan, United States, 48601
Saint John Macomb-Oakland Hospital
Warren, Michigan, United States, 48093
United States, Minnesota
Medini, Eitan MD (UIA Investigator)
Alexandria, Minnesota, United States, 56308
Harris, John Gilbert MD (UIA Investigator)
Alexandria, Minnesota, United States, 56308
Sanford Clinic North-Bemidgi
Bemidji, Minnesota, United States, 56601
Brainerd Medical Center Inc
Brainerd, Minnesota, United States, 56401
Essentia Health Saint Joseph's Medical Center
Brainerd, Minnesota, United States, 56401
Essentia Health Duluth Clinic CCOP
Duluth, Minnesota, United States, 55805
Essentia Health Saint Mary's Medical Center
Duluth, Minnesota, United States, 55805
Miller-Dwan Hospital
Duluth, Minnesota, United States, 55805
Swenson, Wade II, MD (UIA Investigator)
Fergus Falls, Minnesota, United States, 56537
Etzell, Paul S MD (UIA Investigator)
Fergus Falls, Minnesota, United States, 56537
Meeker County Memorial Hospital
Litchfield, Minnesota, United States, 55355
Virginia Piper Cancer Institute
Minneapolis, Minnesota, United States, 55407
Chippewa County - Montevideo Hospital
Montevideo, Minnesota, United States, 56265
Mayo Clinic
Rochester, Minnesota, United States, 55905
CentraCare Clinic
Saint Cloud, Minnesota, United States, 56303
Saint Cloud Hospital
Saint Cloud, Minnesota, United States, 56303
Saint Joseph's Hospital - Healtheast
Saint Paul, Minnesota, United States, 55102
Adult and Pediatric Urology PLLP
Sartell, Minnesota, United States, 56377
Woodwinds Health Campus
Woodbury, Minnesota, United States, 55125
United States, Montana
Saint Vincent Healthcare
Billings, Montana, United States, 59101
Billings Clinic
Billings, Montana, United States, 59107-7000
Deaconess Medical Center
Billings, Montana, United States, 59107
Northern Rockies Radiation Oncology Center
Billings, Montana, United States, 59101
Montana Cancer Consortium CCOP
Billings, Montana, United States, 59101
Hematology-Oncology Centers of the Northern Rockies PC
Billings, Montana, United States, 59102
Bozeman Deaconess Cancer Center
Bozeman, Montana, United States, 59715
Bozeman Deaconess Hospital
Bozeman, Montana, United States, 59715
Internal Medicine of Bozeman
Bozeman, Montana, United States, 59715
Saint James Community Hospital and Cancer Treatment Center
Butte, Montana, United States, 59701
Saint Peter's Community Hospital
Helena, Montana, United States, 59601
Glacier Oncology PLLC
Kalispell, Montana, United States, 59901
Community Medical Hospital
Missoula, Montana, United States, 59801
Montana Cancer Specialists
Missoula, Montana, United States, 59802
Saint Patrick Hospital - Community Hospital
Missoula, Montana, United States, 59802
United States, Nebraska
Fremont Area Medical Center
Fremont, Nebraska, United States, 68025
Bryan LGH Medical Center East
Lincoln, Nebraska, United States, 68506
Bryan LGH Medical Center West
Lincoln, Nebraska, United States, 68502
Saint Elizabeth Regional Medical Center
Lincoln, Nebraska, United States, 68510
Midlands Community Hospital
Papillion, Nebraska, United States, 68046
United States, North Dakota
Bismarck Cancer Center
Bismarck, North Dakota, United States, 58501
Mid Dakota Clinic
Bismarck, North Dakota, United States, 58501
Saint Alexius Medical Center
Bismarck, North Dakota, United States, 58501
Sanford Bismarck Medical Center
Bismarck, North Dakota, United States, 58501
Sanford Clinic North-Fargo
Fargo, North Dakota, United States, 58122
Sanford Medical Center-Fargo
Fargo, North Dakota, United States, 58122
United States, Virginia
University of Virginia
Charlottesville, Virginia, United States, 22908
United States, Wyoming
Welch Cancer Center
Sheridan, Wyoming, United States, 82801
Sponsors and Collaborators
Investigators
Principal Investigator: Paul Brown North Central Cancer Treatment Group
  More Information

No publications provided by National Cancer Institute (NCI)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00039494     History of Changes
Other Study ID Numbers: NCI-2009-00640, N0177, CDR0000069388, NCCTG-N0177, U10CA025224
Study First Received: June 6, 2002
Last Updated: August 1, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Glioblastoma
Gliosarcoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Erlotinib
Temozolomide
Dacarbazine
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents, Alkylating
Alkylating Agents
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 16, 2014