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

Adult Glioblastoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00039494
• Other study ID #: NCI-2009-00640
• Secondary ID: N0177CDR00000693
• Status: Completed
• Phase: Phase 2
• First received: June 6, 2002
• Last updated: August 1, 2013
• Start date: December 2002

Study information

• Verified date: August 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 171
• Est. primary completion date: July 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adult Giant Cell Glioblastoma
• Adult Glioblastoma
• Adult Gliosarcoma
• Glioblastoma
• Gliosarcoma

Intervention

Drug:
• erlotinib hydrochloride
Given orally

Radiation:
• 3-dimensional conformal radiation therapy

Drug:
• temozolomide
Given orally

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Survival		At 52 weeks	No
Primary	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	No
Secondary	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	No
Secondary	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	Yes