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

Study Overview
=================
Brief Summary
-----------------
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.

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.

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

Conditions
-----------------
CNS Tumor, Adult

Intervention / Treatment
-----------------
* Drug: erlotinib hydrochloride
* Drug: temozolomide
* Radiation: radiation therapy


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Radiation Therapy, Temozolomide, and Erlotinib<br> | Drug: erlotinib hydrochloride<br>* 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.<br>* Other names: Tarceva;Drug: temozolomide<br>* 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.<br>* Other names: Temodar;Radiation: radiation therapy<br>* 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.<br>* Other names: RT;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival |  | at 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
adult glioblastoma, adult giant cell glioblastoma, adult gliosarcoma