Radiation Therapy, Temozolomide, and Erlotinib in Treating Patients With Newly Diagnosed Glioblastoma Multiforme

A Phase II Trial of Erlotinib With Temozolomide and Concurrent Radiation Therapy Post-Operatively in Patients With Newly Diagnosed Glioblastoma Multiforme

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving radiation therapy together with temozolomide and erlotinib after surgery may kill any remaining tumor cells.

PURPOSE: This phase II trial is studying how well giving radiation therapy together with temozolomide and erlotinib works in treating patients with newly diagnosed glioblastoma multiforme.

Study Overview

• Status: Completed
• Conditions: CNS Tumor, Adult
• Intervention / Treatment: Drug: erlotinib hydrochloride; Drug: temozolomide; Radiation: radiation therapy

Detailed Description

OBJECTIVES:

• Determine the progression-free survival and overall survival of patients with newly diagnosed glioblastoma multiforme treated with adjuvant radiotherapy, temozolomide, and erlotinib hydrochloride.
• Evaluate the toxicity of this regimen in these patients.

OUTLINE: This is a non-randomized study.

Patients receive oral temozolomide once daily on days 1-42 and undergo concurrent radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40. Four weeks after completion of radiotherapy and temozolomide, patients receive oral temozolomide once daily on days 1-5. Treatment with temozolomide repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients also receive oral erlotinib hydrochloride once daily beginning on day 1 of radiotherapy and continuing in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically proven glioblastoma multiforme

  • Newly diagnosed disease
• Has undergone diagnostic biopsy or surgical resection within the past 28 days

PATIENT CHARACTERISTICS:

• ECOG 0-2
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin > 9 g/L
• Serum creatinine and total serum bilirubin < 1.5 times upper limit of normal (ULN)
• AST or ALT < 2.5 times ULN
• Alkaline phosphatase < 2.5 times ULN
• No other severe underlying disease (including HIV or chronic hepatitis B or C infection)
• Fertile patients must use effective contraception
• Not pregnant or nursing
• No medical condition that could interfere with the oral administration of temozolomide or erlotinib hydrochloride
• No other malignancy within the past 3 years with the exception of surgically cured carcinoma in situ of the cervix, nonmelanoma skin cancer, or adequately treated stage I or II cancer from which the patient is in complete remission
• No active infection
• No other condition that would preclude ability of the patient to be followed closely at the Cleveland Clinic

PRIOR CONCURRENT THERAPY:

• No prior radiotherapy or chemotherapy for this cancer
• No prior cranial radiotherapy
• No concurrent enzyme-inducing anti-epileptic drugs
• No prior temozolomide or erlotinib hydrochloride
• No other concurrent antineoplastic therapy
• No concurrent filgrastim (G-CSF) or sargramostim (GM-CSF) during chemotherapy
• No concurrent electron, particle, or implant boost radiotherapy
• No concurrent radiosurgery

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Radiation Therapy, Temozolomide, and Erlotinib

Drug: erlotinib hydrochloride; Erlotinib is available as 25 mg, 100 mg, and 150 mg tablets. It should be administered orally once daily at the prescribed dose specified in the clinical study protocol per dose escalation schema. Preferably, erlotinib should be taken in the morning with up to 200 mL of water at least 1 hour before or 2 hours after a meal.; Other Names: Tarceva; Drug: temozolomide; TMZ is supplied in white opaque, preservative-free, two piece hard gelatin capsules of the following sizes: 100mg capsules, 20mg capsules, and 5mg capsules. TMZ will be a once a day orally administered (75 mg/m2 x BSA x 42 days)set of capsules taken at least two hours after and one hour before a meal.; Other Names: Temodar; Radiation: radiation therapy; Concomitant focal RT will be delivered once daily at 2 Gy per fraction, 5 d/wk, for a total of 60 Gy. (6 weeks) as mentioned in therapeutic modalities.; Other Names: RT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Progression-free survival	at 6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Progression Free Survival	at 1 yr
Number of patients that experience toxicity (CTCAE V2)	at 6 months
Overall Survival	date of final follow up visit

Collaborators and Investigators

• Sponsor: David Peereboom
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: David M. Peereboom, MD, Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start: October 1, 2005
• Primary Completion (Actual): October 1, 2007
• Study Completion (Actual): September 1, 2012

Study Registration Dates

• First Submitted: January 10, 2006
• First Submitted That Met QC Criteria: January 10, 2006
• First Posted (Estimate): January 11, 2006

Study Record Updates

• Last Update Posted (Estimate): December 6, 2012
• Last Update Submitted That Met QC Criteria: December 5, 2012
• Last Verified: December 1, 2012

More Information

Terms related to this study

• Keywords: adult glioblastoma; adult giant cell glioblastoma; adult gliosarcoma
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nervous System Neoplasms; Glioblastoma; Central Nervous System Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Protein Kinase Inhibitors; Erlotinib Hydrochloride; Temozolomide
• Other Study ID Numbers: CASE3304 (Other Identifier: Case Comprehensive Cancer Center); P30CA043703 (U.S. NIH Grant/Contract); CCF-6320 (Other Identifier: Cleveland Clinic IRB)