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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
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Study Description
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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.

Condition or disease Intervention/treatment Phase
Adult Giant Cell Glioblastoma Adult Glioblastoma Adult Gliosarcoma Drug: erlotinib hydrochloride Radiation: 3-dimensional conformal radiation therapy Drug: temozolomide Phase 2

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 171 participants
Allocation: N/A
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

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
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.
 Drug: erlotinib hydrochloride
Given orally
Other Names:
  • CP-358,774
  • erlotinib
  • OSI-774

Radiation: 3-dimensional conformal radiation therapy
Other Names:
  • 3D conformal radiation therapy
  • 3D-CRT

Drug: temozolomide
Given orally
Other Names:
  • SCH 52365
  • Temodal
  • Temodar
  • TMZ


Outcome Measures
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Primary Outcome Measures :
  1. Survival [ Time Frame: At 52 weeks ]
  2. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

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


Locations
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Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Paul Brown North Central Cancer Treatment Group
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00039494    
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:
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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
Erlotinib Hydrochloride
Temozolomide
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Alkylating
Alkylating Agents