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

Phase 2

Completed

Brief Summary: 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: 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

Recruitment & Eligibility

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

Exclusion Criteria

Not provided

Arm && Interventions

Group	Intervention	Description
Whole brain irradiation plus Temozolomide	Whole brain irradiation	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.
Whole brain irradiation	Whole brain irradiation	Whole brain irradiation at a dose of 30 Gy in 10 daily fractions over 2 weeks
Whole brain irradiation plus Temozolomide	Temozolomide	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.

Primary Outcome Measures

Name	Time	Method
Objective Response Rates. Assessed With Cranial MRI	90 days	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.

Secondary Outcome Measures

Name	Time	Method
Survival Free of Brain Metastases Progression (PFS of BM)	at 90 days	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.
Overall Survival	1 year	Overall survival:Time in months measured from treatment initiation until the date of death or the date of last follow-up.
Number of Grade 3-4 Adverse Events (AE) That Are Definitely or Probably Related to Both Groups of Treatment.	4 months	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.