Erlotinib and Temozolomide With Radiation Therapy in Treating Patients With Glioblastoma Multiforme or Other Brain Tumors
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ClinicalTrials.gov Identifier: NCT00039494 |
Recruitment Status :
Completed
First Posted : January 27, 2003
Last Update Posted : August 2, 2013
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Condition or disease | Intervention/treatment | Phase |
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Adult Giant Cell Glioblastoma Adult Glioblastoma Adult Gliosarcoma | Drug: erlotinib hydrochloride Radiation: 3-dimensional conformal radiation therapy Drug: temozolomide | Phase 2 |
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 (Clinical Trial) |
Estimated Enrollment : | 171 participants |
Intervention Model: | Single Group Assignment |
Masking: | None (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 |
Study Start Date : | December 2002 |
Actual Primary Completion Date : | July 2007 |

Arm | Intervention/treatment |
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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.
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Drug: erlotinib hydrochloride
Given orally
Other Names:
Radiation: 3-dimensional conformal radiation therapy Other Names:
Drug: temozolomide Given orally
Other Names:
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- Survival [ Time Frame: At 52 weeks ]
- Overall survival distribution [ Time Frame: From start of study therapy to death due to any cause, up to 15 years ]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.
- Time-to-disease progression [ Time Frame: From start of study therapy to documentation of disease progression, up to 15 years ]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 ]Frequency tables will be reviewed to determine toxicity patterns.

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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
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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

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00039494

Principal Investigator: | Paul Brown | North Central Cancer Treatment Group |
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 ( U.S. NIH Grant/Contract ) |
First Posted: | January 27, 2003 Key Record Dates |
Last Update Posted: | August 2, 2013 |
Last Verified: | August 2013 |
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 Temozolomide Erlotinib Hydrochloride Dacarbazine Antineoplastic Agents Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antineoplastic Agents, Alkylating Alkylating Agents |