Whole Brain Radiotherapy With or Without Temozolomide at Daily Fixed-dose for Brain Metastases Treatment

Study Overview
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Brief Summary
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RATIONALE Fractionated radiotherapy uses high-energy photons to kill, or damage tumor cells. High daily dose temozolomide combined with fractionated radiotherapy may make tumor cells more sensible to treatment. PURPOSE This randomized phase II trial, assess in patients with brain metastases from solid tumors, whether the whole brain radiotherapy (WBRT) plus temozolomide is able to improve the results obtained with WBRT.

Detailed Description
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Primary Outcome Measures Objective Response Rates Secondary Outcome Measures Survival Free of Brain Metastases progression Overall Survival Systemic Side effects Objectives Primary Compare objective response rates in both arms of treatment Secondary Compare survival free of progression in both arms of treatment Compare Overall Survival in both arms of treatment Compare side effects

Official Title
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Phase II Randomized Study: Whole Brain Radiotherapy and Concomitant Temozolomide, Compared With Whole Brain Radiotherapy for Brain Metastases Treatment

Conditions
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Brain Neoplasms

Intervention / Treatment
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* Drug: Temozolomide
* Radiation: Whole brain irradiation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Karnofsky performance status (KPS) ≥ 50 Life expectancy ≥ 12 weeks Histologically confirmed non lymphomatous solid tumors at primary site Brain metastases diagnosed with cranial MRI/CT. Extracranial metastases or primary tumor uncontrolled are allowed Hemoglobin ≥ 10 g/dl Absolute neutrophil count of > 1500/mm3 Platelet count of ≥ 100,000/mm3 Blood urea nitrogen (BUN) ≤ 25 mg/dl, Serum creatinin ≤ 1.5 mg/dl Serum bilirubins ≤ 1.5 mg/dl, Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) ≤ twice the upper normal limit Exclusion Criteria Pregnant or breast feeding woman History of allergic reaction to iodinated contrast media Inability to swallow Systemic chemotherapy in previous 3 weeks Oral chemotherapy in previous 2 weeks Prior surgery, chemotherapy, or radiotherapy for a brain neoplasm Meningeal carcinomatosis

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Whole brain irradiation plus Temozolomide<br>Whole brain irradiation at a dose of 30 Gy in 10 daily fractions over 2 weeks, and a fixed dose of oral Temozolomide, 1h before each fraction of whole brain irradiation, 200 mg on Monday, Wednesday, Friday; 300 mg on Tuesday, and Thursday. Without adjuvant cycles of Temozolomide. | Drug: Temozolomide<br> <br> * Other names: Temodal;Radiation: Whole brain irradiation<br> <br> * Other names: Whole brain radiotherapy;|
| Active Comparator: Whole brain irradiation<br>Whole brain irradiation at a dose of 30 Gy in 10 daily fractions over 2 weeks | Radiation: Whole brain irradiation<br> <br> * Other names: Whole brain radiotherapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rates. Assessed With Cranial MRI | Objective Response (OR) encompassed the number of participants with Complete Response (CR) and the number of participants with Partial Response (PR). CR is the disappearance of all brain metastases, assessed between two or more cranial MRI. PR is at least a 30% decrease in the sum of the longest diameter of the brain metastases, taking as reference the baseline sum longest diameter, assessed between two or more cranial MRI. Objective Response Rate (ORR) is the ratio between the number of participants with objective response and the total number of participants. | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival Free of Brain Metastases Progression (PFS of BM) | Progression free survival of brain metastases is the survival of participants without progressive brain metastases or without neurological symptoms. The progressive brain metastases (PBM) were evaluated with cranial MRI. The PBM were defined as an increase of at least 20% in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new metastases. | at 90 days | 
| Overall Survival | Overall survival:Time in months measured from treatment initiation until the date of death or the date of last follow-up. | 1 year | 
| Number of Grade 3-4 Adverse Events (AE) That Are Definitely or Probably Related to Both Groups of Treatment. | AE, evaluated and graded according to the NCI common terminology criteria (NCI-CTCAE) v3.0 Grade 3 Severe AE. Grade 4 Life-threatening or disabling AE. | 4 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Brain metastases, Temozolomide, Whole-brain radiotherapy, Phase II trial