Clinical trial NCT00039494: Erlotinib and Temozolomide With Radiation Therapy in Treating Patients With Glioblastoma Multiforme or Other Brain Tumors
Official title: A Pilot and Phase II Study of OSI-774 and Temozolomide in Combination With Radiation Therapy in Glioblastoma Multiforme
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Adult Giant Cell Glioblastoma
Adult Glioblastoma
Adult Gliosarcoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-01-27
Enrollment: 171
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Survival
timeFrame: At 52 weeks
measure: Overall survival distribution
timeFrame: From start of study therapy to death due to any cause, up to 15 years
Secondary outcomes:
measure: Time-to-disease progression
timeFrame: From start of study therapy to documentation of disease progression, up to 15 years
measure: Maximum toxicity grade, assessed by Common Terminology Criteria for Adverse Events (CTCAE)
timeFrame: Up to 15 years
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Mobile Infirmary Medical Center
state: Alabama
city: Scottsdale
country: United States
facility: Mayo Clinic in Arizona
state: Arizona
city: Jacksonville
country: United States
facility: Mayo Clinic in Florida
state: Florida
city: Athens
country: United States
facility: Northeast Georgia Cancer Care LLC
state: Georgia
city: Aurora
country: United States
facility: Rush - Copley Medical Center
state: Illinois
city: Bloomington
country: United States
facility: Saint Joseph Medical Center
state: Illinois
city: Canton
country: United States
facility: Graham Hospital Association
state: Illinois
city: Carthage
country: United States
facility: Memorial Hospital
state: Illinois
city: Effingham
country: United States
facility: Saint Anthony Memorial Hospital
state: Illinois
city: Eureka
country: United States
facility: Eureka Hospital
state: Illinois
city: Galesburg
country: United States
facility: Galesburg Cottage Hospital
state: Illinois
city: Galesburg
country: United States
facility: Illinois CancerCare Galesburg
state: Illinois
city: Galesburg
country: United States
facility: Western Illinois Cancer Treatment Center
state: Illinois
city: Havana
country: United States
facility: Mason District Hospital
state: Illinois
city: Hopedale
country: United States
facility: Hopedale Medical Complex - Hospital
state: Illinois
city: Joliet
country: United States
facility: Joliet Oncology-Hematology Associates Limited
state: Illinois
city: Kewanee
country: United States
facility: Kewanee Hospital
state: Illinois
city: Macomb
country: United States
facility: Mcdonough District Hospital
state: Illinois
city: Moline
country: United States
facility: Garneau, Stewart C MD (UIA Investigator)
state: Illinois
city: Moline
country: United States
facility: Porubcin, Michael MD (UIA Investigator)
state: Illinois
city: Moline
country: United States
facility: Sharis, Christine M MD (UIA Investigator)
state: Illinois
city: Moline
country: United States
facility: Stoffel, Thomas J MD (UIA Investigator)
state: Illinois
city: Moline
country: United States
facility: Vigliotti, Antonio, P.G. M.D. (UIA Investigator)
state: Illinois
city: Normal
country: United States
facility: Bromenn Regional Medical Center
state: Illinois
city: Normal
country: United States
facility: Community Cancer Center Foundation
state: Illinois
city: Ottawa
country: United States
facility: Illinois CancerCare-Ottawa Clinic
state: Illinois
city: Ottawa
country: United States
facility: Ottawa Regional Hospital and Healthcare Center
state: Illinois
city: Pekin
country: United States
facility: Pekin Cancer Treatment Center
state: Illinois
city: Pekin
country: United States
facility: Pekin Hospital
state: Illinois
city: Peoria
country: United States
facility: Methodist Medical Center of Illinois
state: Illinois
city: Peoria
country: United States
facility: Proctor Hospital
state: Illinois
city: Peoria
country: United States
facility: Illinois CancerCare-Peoria
state: Illinois
city: Peoria
country: United States
facility: Illinois Oncology Research Association CCOP
state: Illinois
city: Peoria
country: United States
facility: OSF Saint Francis Medical Center
state: Illinois
city: Peru
country: United States
facility: Illinois Valley Hospital
state: Illinois
city: Princeton
country: United States
facility: Perry Memorial Hospital
state: Illinois
city: Spring Valley
country: United States
facility: Saint Margaret's Hospital
state: Illinois
city: Spring Valley
country: United States
facility: Valley Cancer Center
state: Illinois
city: Urbana
country: United States
facility: Carle Clinic-Urbana Main
state: Illinois
city: Michigan City
country: United States
facility: Saint Anthony Memorial Health Center
state: Indiana
city: Ames
country: United States
facility: McFarland Clinic
state: Iowa
city: Bettendorf
country: United States
facility: Constantinou, Costas L MD (UIA Investigator)
state: Iowa
city: Carroll
country: United States
facility: Saint Anthony Regional Hospital
state: Iowa
city: Cedar Rapids
country: United States
facility: Saint Luke's Hospital
state: Iowa
city: Cedar Rapids
country: United States
facility: Cedar Rapids Oncology Association
state: Iowa
city: Cedar Rapids
country: United States
facility: Mercy Hospital
state: Iowa
city: Cedar Rapids
country: United States
facility: Oncology Associates at Mercy Medical Center
state: Iowa
city: Clive
country: United States
facility: Medical Oncology and Hematology Associates-West Des Moines
state: Iowa
city: Council Bluffs
country: United States
facility: Alegent Health Mercy Hospital
state: Iowa
city: Des Moines
country: United States
facility: Mercy Capitol
state: Iowa
city: Des Moines
country: United States
facility: Iowa Methodist Medical Center
state: Iowa
city: Des Moines
country: United States
facility: Iowa Oncology Research Association CCOP
state: Iowa
city: Des Moines
country: United States
facility: Medical Oncology and Hematology Associates-Des Moines
state: Iowa
city: Des Moines
country: United States
facility: Medical Oncology and Hematology Associates
state: Iowa
city: Des Moines
country: United States
facility: Mercy Medical Center - Des Moines
state: Iowa
city: Des Moines
country: United States
facility: Iowa Lutheran Hospital
state: Iowa
city: Missouri Valley
country: United States
facility: Community Memorial Hospital
state: Iowa
city: Onawa
country: United States
facility: Burgess Memorial Hospital
state: Iowa
city: Sioux City
country: United States
facility: Siouxland Regional Cancer Center
state: Iowa
city: Sioux City
country: United States
facility: Siouxland Hematology Oncology Associates
state: Iowa
city: Sioux City
country: United States
facility: Mercy Medical Center-Sioux City
state: Iowa
city: Sioux City
country: United States
facility: Saint Luke's Regional Medical Center
state: Iowa
city: Anthony
country: United States
facility: Hospital District Sixth of Harper County
state: Kansas
city: Chanute
country: United States
facility: Cancer Center of Kansas - Chanute
state: Kansas
city: Dodge City
country: United States
facility: Cancer Center of Kansas - Dodge City
state: Kansas
city: El Dorado
country: United States
facility: Cancer Center of Kansas - El Dorado
state: Kansas
city: Fort Scott
country: United States
facility: Cancer Center of Kansas - Fort Scott
state: Kansas
city: Independence
country: United States
facility: Cancer Center of Kansas-Independence
state: Kansas
city: Kingman
country: United States
facility: Cancer Center of Kansas-Kingman
state: Kansas
city: Lawrence
country: United States
facility: Lawrence Memorial Hospital
state: Kansas
city: Newton
country: United States
facility: Cancer Center of Kansas - Newton
state: Kansas
city: Parsons
country: United States
facility: Cancer Center of Kansas - Parsons
state: Kansas
city: Pratt
country: United States
facility: Cancer Center of Kansas - Pratt
state: Kansas
city: Salina
country: United States
facility: Cancer Center of Kansas - Salina
state: Kansas
city: Wellington
country: United States
facility: Cancer Center of Kansas - Wellington
state: Kansas
city: Wichita
country: United States
facility: Associates In Womens Health
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas-Wichita Medical Arts Tower
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas - Main Office
state: Kansas
city: Wichita
country: United States
facility: Via Christi Regional Medical Center
state: Kansas
city: Wichita
country: United States
facility: Wesley Medical Center
state: Kansas
city: Wichita
country: United States
facility: Wichita CCOP
state: Kansas
city: Winfield
country: United States
facility: Cancer Center of Kansas - Winfield
state: Kansas
city: Ann Arbor
country: United States
facility: Saint Joseph Mercy Hospital
state: Michigan
city: Ann Arbor
country: United States
facility: Michigan Cancer Research Consortium Community Clinical Oncology Program
state: Michigan
city: Dearborn
country: United States
facility: Oakwood Hospital
state: Michigan
city: Detroit
country: United States
facility: Saint John Hospital and Medical Center
state: Michigan
city: Flint
country: United States
facility: Hurley Medical Center
state: Michigan
city: Flint
country: United States
facility: Genesys Regional Medical Center-West Flint Campus
state: Michigan
city: Jackson
country: United States
facility: Allegiance Health
state: Michigan
city: Lansing
country: United States
facility: Sparrow Hospital
state: Michigan
city: Saginaw
country: United States
facility: Saint Mary's of Michigan
state: Michigan
city: Warren
country: United States
facility: Saint John Macomb-Oakland Hospital
state: Michigan
city: Alexandria
country: United States
facility: Harris, John Gilbert MD (UIA Investigator)
state: Minnesota
city: Alexandria
country: United States
facility: Medini, Eitan MD (UIA Investigator)
state: Minnesota
city: Bemidji
country: United States
facility: Sanford Clinic North-Bemidgi
state: Minnesota
city: Brainerd
country: United States
facility: Brainerd Medical Center Inc
state: Minnesota
city: Brainerd
country: United States
facility: Essentia Health Saint Joseph's Medical Center
state: Minnesota
city: Duluth
country: United States
facility: Essentia Health Duluth Clinic CCOP
state: Minnesota
city: Duluth
country: United States
facility: Essentia Health Saint Mary's Medical Center
state: Minnesota
city: Duluth
country: United States
facility: Miller-Dwan Hospital
state: Minnesota
city: Fergus Falls
country: United States
facility: Etzell, Paul S MD (UIA Investigator)
state: Minnesota
city: Fergus Falls
country: United States
facility: Swenson, Wade II, MD (UIA Investigator)
state: Minnesota
city: Litchfield
country: United States
facility: Meeker County Memorial Hospital
state: Minnesota
city: Minneapolis
country: United States
facility: Virginia Piper Cancer Institute
state: Minnesota
city: Montevideo
country: United States
facility: Chippewa County - Montevideo Hospital
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Cloud
country: United States
facility: CentraCare Clinic
state: Minnesota
city: Saint Cloud
country: United States
facility: Saint Cloud Hospital
state: Minnesota
city: Saint Paul
country: United States
facility: Saint Joseph's Hospital - Healtheast
state: Minnesota
city: Sartell
country: United States
facility: Adult and Pediatric Urology PLLP
state: Minnesota
city: Woodbury
country: United States
facility: Woodwinds Health Campus
state: Minnesota
city: Billings
country: United States
facility: Montana Cancer Consortium CCOP
state: Montana
city: Billings
country: United States
facility: Northern Rockies Radiation Oncology Center
state: Montana
city: Billings
country: United States
facility: Saint Vincent Healthcare
state: Montana
city: Billings
country: United States
facility: Hematology-Oncology Centers of the Northern Rockies PC
state: Montana
city: Billings
country: United States
facility: Billings Clinic
state: Montana
city: Billings
country: United States
facility: Deaconess Medical Center
state: Montana
city: Bozeman
country: United States
facility: Bozeman Deaconess Cancer Center
state: Montana
city: Bozeman
country: United States
facility: Bozeman Deaconess Hospital
state: Montana
city: Bozeman
country: United States
facility: Internal Medicine of Bozeman
state: Montana
city: Butte
country: United States
facility: Saint James Community Hospital and Cancer Treatment Center
state: Montana
city: Helena
country: United States
facility: Saint Peter's Community Hospital
state: Montana
city: Kalispell
country: United States
facility: Glacier Oncology PLLC
state: Montana
city: Missoula
country: United States
facility: Community Medical Hospital
state: Montana
city: Missoula
country: United States
facility: Montana Cancer Specialists
state: Montana
city: Missoula
country: United States
facility: Saint Patrick Hospital - Community Hospital
state: Montana
city: Fremont
country: United States
facility: Fremont Area Medical Center
state: Nebraska
city: Lincoln
country: United States
facility: Bryan LGH Medical Center West
state: Nebraska
city: Lincoln
country: United States
facility: Bryan LGH Medical Center East
state: Nebraska
city: Lincoln
country: United States
facility: Saint Elizabeth Regional Medical Center
state: Nebraska
city: Papillion
country: United States
facility: Midlands Community Hospital
state: Nebraska
city: Bismarck
country: United States
facility: Bismarck Cancer Center
state: North Dakota
city: Bismarck
country: United States
facility: Mid Dakota Clinic
state: North Dakota
city: Bismarck
country: United States
facility: Saint Alexius Medical Center
state: North Dakota
city: Bismarck
country: United States
facility: Sanford Bismarck Medical Center
state: North Dakota
city: Fargo
country: United States
facility: Sanford Clinic North-Fargo
state: North Dakota
city: Fargo
country: United States
facility: Sanford Medical Center-Fargo
state: North Dakota
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Sheridan
country: United States
facility: Welch Cancer Center
state: Wyoming
Study officials:
affiliation: North Central Cancer Treatment Group
name: Paul Brown
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.