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

A Pilot and Phase II Study of OSI-774 and Temozolomide in Combination With Radiation Therapy in Glioblastoma Multiforme

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.

Study Overview

• Status: Completed
• Conditions: Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma
• Intervention / Treatment: Drug: erlotinib hydrochloride; Radiation: 3-dimensional conformal radiation therapy; Drug: temozolomide

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.

• Study Type: Interventional
• Enrollment (Anticipated): 171
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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: OSI-774; erlotinib; CP-358,774; Radiation: 3-dimensional conformal radiation therapy; Other Names: 3D-CRT; 3D conformal radiation therapy; Drug: temozolomide; Given orally; Other Names: Temodar; SCH 52365; Temodal; TMZ

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival		At 52 weeks
Overall survival distribution	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.	From start of study therapy to death due to any cause, up to 15 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time-to-disease progression	The time-to-progression distribution will be estimated using the Kaplan-Meier method.	From start of study therapy to documentation of disease progression, up to 15 years
Maximum toxicity grade, assessed by Common Terminology Criteria for Adverse Events (CTCAE)	Frequency tables will be reviewed to determine toxicity patterns.	Up to 15 years

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Paul Brown, North Central Cancer Treatment Group

Publications and helpful links

General Publications

• Brown PD, Krishnan S, Sarkaria JN, Wu W, Jaeckle KA, Uhm JH, Geoffroy FJ, Arusell R, Kitange G, Jenkins RB, Kugler JW, Morton RF, Rowland KM Jr, Mischel P, Yong WH, Scheithauer BW, Schiff D, Giannini C, Buckner JC; North Central Cancer Treatment Group Study N0177. Phase I/II trial of erlotinib and temozolomide with radiation therapy in the treatment of newly diagnosed glioblastoma multiforme: North Central Cancer Treatment Group Study N0177. J Clin Oncol. 2008 Dec 1;26(34):5603-9. doi: 10.1200/JCO.2008.18.0612. Epub 2008 Oct 27.

Study record dates

Study Major Dates

• Study Start: December 1, 2002
• Primary Completion (Actual): July 1, 2007

Study Registration Dates

• First Submitted: June 6, 2002
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): August 2, 2013
• Last Update Submitted That Met QC Criteria: August 1, 2013
• Last Verified: August 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Gliosarcoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Protein Kinase Inhibitors; Erlotinib Hydrochloride; Temozolomide
• Other Study ID Numbers: NCI-2009-00640; U10CA025224 (U.S. NIH Grant/Contract); N0177; CDR0000069388; NCCTG-N0177