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

Show 51 Study Locations

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