Erlotinib and Temozolomide With Radiation Therapy in Treating Patients With Glioblastoma Multiforme or Other Brain Tumors - Full Text View

Sponsor:	North Central Cancer Treatment Group
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00039494

Purpose

RATIONALE: 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.

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.

Condition	Intervention	Phase
Brain and Central Nervous System Tumors	Drug: erlotinib hydrochloride Drug: temozolomide Radiation: radiation therapy	Phase II

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	A Phase I/II Study of OSI-774 and Temozolomide In Combination With Radiation Therapy In Glioblastoma Multiforme

Resource links provided by NLM:

MedlinePlus related topics: Brain Cancer Cancer

Drug Information available for: Temozolomide Erlotinib hydrochloride Erlotinib

U.S. FDA Resources

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

Primary Outcome Measures:

Survival at 52 weeks [ Designated as safety issue: No ]

Secondary Outcome Measures:

Time- to-disease progression [ Designated as safety issue: No ]
Toxicity [ Designated as safety issue: Yes ]

Estimated Enrollment:	171
Study Start Date:	December 2002
Estimated Primary Completion Date:	June 2004 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Pilot study

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.
Determine the safety and tolerability of this regimen in these patients.
Determine the toxic effects of this regimen in these patients.
Determine the efficacy of this regimen, in terms of 1-year survival, in these patients.

Phase II

Determine the response rate and time to progression in patients treated with this regimen.
Determine the 6-month progression-free survival of patients treated with this regimen.
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.

PROJECTED ACCRUAL: A total of 12-78 patients (6-36 not receiving concurrent enzyme-inducing anticonvulsant drugs [EIADs] and 6-42 receiving concurrent EIADs) will be accrued for the pilot portion of this study within 4-12 months. A total of 93 patients will be accrued for the phase II portion of this study within 11 months.

Eligibility

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

Criteria

DISEASE CHARACTERISTICS:

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

PATIENT CHARACTERISTICS:

Age:

18 and over

Performance status:

ECOG 0-2 OR
Karnofsky 60-100%

Life expectancy:

At least 6 months

Hematopoietic:

Absolute neutrophil count at least 1,500/mm^3
Platelet count at least 100,000/mm^3
Hemoglobin ≥ 9 g/dL

Hepatic:

Total bilirubin ≤ upper limit of normal (ULN)
AST no greater than 2.5 times ULN

Renal:

Creatinine no greater than 1.5 times ULN

Cardiovascular:

No symptomatic congestive heart failure
No unstable angina pectoris
No cardiac arrhythmia

Gastrointestinal:

No inability to take oral medications
No requirement for IV alimentation
No active uncontrolled peptic ulcer disease

Ophthalmic:

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)

Other:

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

PRIOR CONCURRENT THERAPY:

Biologic therapy:

Not specified

Chemotherapy:

No prior chemotherapy for any brain tumor
No prior temozolomide

Endocrine therapy:

Not specified

Radiotherapy:

No prior radiotherapy for any brain tumor

Surgery:

See Disease Characteristics
More than 21 days since prior major surgery (excluding neurosurgical biopsy or brain tumor resection)
No prior surgical procedures affecting absorption

Other:

No concurrent combination antiretroviral therapy for HIV-positive patients
No concurrent warfarin
No other concurrent investigational agents

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00039494

Hide Study Locations

Locations

United States, Arizona
Mayo Clinic Scottsdale
Scottsdale, Arizona, United States, 85259-5499
United States, Florida
Mayo Clinic - Jacksonville
Jacksonville, Florida, United States, 32224
United States, Iowa
Mercy Cancer Center at Mercy Medical Center - North Iowa
Mason City, Iowa, United States, 50401
United States, Kansas
Associates in Womens Health, PA - North Review
Wichita, Kansas, United States, 67208
Cancer Center of Kansas - Fort Scott
Fort Scott, Kansas, United States, 66701
Cancer Center of Kansas, PA - Kingman
Kingman, Kansas, United States, 67068
Cancer Center of Kansas, PA - Newton
Newton, Kansas, United States, 67114
Cancer Center of Kansas, PA - Chanute
Chanute, Kansas, United States, 66720
Cancer Center of Kansas, PA - Dodge City
Dodge City, Kansas, United States, 67801
Cancer Center of Kansas, PA - El Dorado
El Dorado, Kansas, United States, 67042
Cancer Center of Kansas, PA - Medical Arts Tower
Wichita, Kansas, United States, 67208
Cancer Center of Kansas, PA - Wichita
Wichita, Kansas, United States, 67214
Cancer Center of Kansas, PA - Parsons
Parsons, Kansas, United States, 67357
Cancer Center of Kansas, PA - Pratt
Pratt, Kansas, United States, 67124
Cancer Center of Kansas, PA - Salina
Salina, Kansas, United States, 67042
Cancer Center of Kansas, PA - Wellington
Wellington, Kansas, United States, 67152
CCOP - Wichita
Wichita, Kansas, United States, 67214
Cancer Center of Kansas-Independence
Independence, Kansas, United States, 67301
Cancer Center of Kansas, PA - Winfield
Winfield, Kansas, United States, 67156
Hospital District Sixth of Harper County
Anthony, Kansas, United States, 67003
Lawrence Memorial Hospital
Lawrence, Kansas, United States, 66044
Southwest Medical Center
Liberal, Kansas, United States, 67901
Via Christi Cancer Center at Via Christi Regional Medical Center
Wichita, Kansas, United States, 67214
Wesley Medical Center
Wichita, Kansas, United States, 67214
United States, Minnesota
CCOP - Metro-Minnesota
Saint Louis Park, Minnesota, United States, 55416
CentraCare Clinic - River Campus
Saint Cloud, Minnesota, United States, 56303
Coborn Cancer Center
Saint Cloud, Minnesota, United States, 56303
Fairview Ridges Hospital
Burnsville, Minnesota, United States, 55337
Fairview Southdale Hospital
Edina, Minnesota, United States, 55435
HealthEast Cancer Care at St. John's Hospital
Maplewood, Minnesota, United States, 55109
Hennepin County Medical Center - Minneapolis
Minneapolis, Minnesota, United States, 55415
Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center
Robbinsdale, Minnesota, United States, 55422-2900
Mercy and Unity Cancer Center at Unity Hospital
Fridley, Minnesota, United States, 55432

Alexandria, Minnesota, United States, 56308
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905
Meeker County Memorial Hospital
Lichfield, Minnesota, United States, 55355
Mercy and Unity Cancer Center at Mercy Hospital
Coon Rapids, Minnesota, United States, 55433
Hutchinson Area Health Care
Hutchinson, Minnesota, United States, 55350
Minnesota Oncology Hematology, PA - Maplewood
Maplewood, Minnesota, United States, 55109
Minnesota Oncology Hematology, PA - Woodbury
Woodbury, Minnesota, United States, 55125
Park Nicollet Cancer Center
Saint Louis Park, Minnesota, United States, 55416
Regions Hospital Cancer Care Center
St. Paul, Minnesota, United States, 55101
United Hospital
Saint Paul, Minnesota, United States, 55102
St. Francis Cancer Center at St. Francis Medical Center
Shakopee, Minnesota, United States, 55379
Ridgeview Medical Center
Waconia, Minnesota, United States, 55387
Virginia Piper Cancer Institute at Abbott - Northwestern Hospital
Minneapolis, Minnesota, United States, 55407
United States, North Dakota
Bismarck Cancer Center
Bismarck, North Dakota, United States, 58501
Medcenter One Hospital Cancer Care Center
Bismarck, North Dakota, United States, 58501
Mid Dakota Clinic, PC
Bismarck, North Dakota, United States, 58501
St. Alexius Medical Center Cancer Center
Bismarck, North Dakota, United States, 58502
United States, Virginia
University of Virginia Cancer Center
Charlottesville, Virginia, United States, 22908

Sponsors and Collaborators

North Central Cancer Treatment Group

National Cancer Institute (NCI)

Investigators

Study Chair:

Paul D. Brown, MD

Mayo Clinic

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

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. Phase I/II Trial 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 Oct 27; [Epub ahead of print]

Krishnan S, Brown PD, Ballman KV, Fiveash JB, Uhm JH, Giannini C, Jaeckle KA, Geoffroy FJ, Nabors LB, Buckner JC. Phase I trial of erlotinib with radiation therapy in patients with glioblastoma multiforme: Results of north central cancer treatment group protocol n0177. Int J Radiat Oncol Biol Phys. 2006 Apr 18; [Epub ahead of print]

Responsible Party:	North Central Cancer Treatment Group ( Jan C. Buckner )
Study ID Numbers:	CDR0000069388, NCCTG-N0177
Study First Received:	June 6, 2002
Last Updated:	November 10, 2009
ClinicalTrials.gov Identifier:	NCT00039494 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):

adult glioblastoma
adult giant cell glioblastoma
adult gliosarcoma

Additional relevant MeSH terms:

Erlotinib
Glioblastoma
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Astrocytoma
Antineoplastic Agents
Nervous System Diseases
Neoplasms, Nerve Tissue
Enzyme Inhibitors
Central Nervous System Neoplasms
Protein Kinase Inhibitors
Temozolomide

Pharmacologic Actions
Neuroectodermal Tumors
Neoplasms
Neoplasms by Site
Therapeutic Uses
Neoplasms, Germ Cell and Embryonal
Antineoplastic Agents, Alkylating
Glioma
Neoplasms, Neuroepithelial
Alkylating Agents
Nervous System Neoplasms
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on November 30, 2009