Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Closed	18 and over	NCI	NCCTG-N0177 NCT00039494, N0177

Objectives

Pilot study

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

Phase II

1. Determine the response rate and time to progression in patients treated with this regimen.
2. Determine the 6-month progression-free survival of patients treated with this regimen.
3. Determine the toxic effects of this regimen in these patients.

Entry 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

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

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/mm³
• Platelet count at least 100,000/mm³
• 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

Expected Enrollment

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.

Outcomes

Survival at 52 weeks

Time- to-disease progression
Toxicity

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.

Brown PD, Krishnan S, Sarkaria JN, et al.: 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 26 (34): 5603-9, 2008.[PUBMED Abstract]

Krishnan S, Brown PD, Ballman KV, et al.: 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 65 (4): 1192-9, 2006.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

North Central Cancer Treatment Group

Paul Brown, MD, Protocol chair		Ph: 507-538-7623 Email: cancerclinicaltrials@mayo.edu

Registry Information
Official Title		A Phase I/II Study of OSI-774 and Temozolomide In Combination With Radiation Therapy In Glioblastoma Multiforme
Trial Start Date		2002-12-13
Trial Completion Date		2004-06-17 (estimated)
Registered in ClinicalTrials.gov		NCT00039494
Date Submitted to PDQ		2002-04-19
Information Last Verified		2009-09-15
NCI Grant/Contract Number		CA25224

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