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

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


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

Resource links provided by the National Library of Medicine

Drug Information available for: Temozolomide Erlotinib hydrochloride Erlotinib

Genetic and Rare Diseases Information Center resources: Glioblastoma Gliosarcoma Glioma Neuroepithelioma

U.S. FDA Resources

Arms and Interventions

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

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

Primary Outcome Measures :

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.

Secondary Outcome Measures :

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.

Eligibility Criteria

Information from the National Library of Medicine

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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

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

Show 139 Study Locations

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators


Principal Investigator:	Paul Brown	North Central Cancer Treatment Group

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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; North Central Cancer Treatment Group Study N0177. 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. 2008 Dec 1;26(34):5603-9. doi: 10.1200/JCO.2008.18.0612. Epub 2008 Oct 27.


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

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