search
Back to results

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

Primary Purpose

Brain Neoplasms

Status
Completed
Phase
Phase 2
Locations
Mexico
Study Type
Interventional
Intervention
Temozolomide
Whole brain irradiation
Sponsored by
Instituto Nacional de Cancerologia de Mexico
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Brain Neoplasms focused on measuring Brain metastases, Temozolomide, Whole-brain radiotherapy, Phase II trial

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Instituto Nacional de Cancerología de México

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Whole brain irradiation plus Temozolomide

Whole brain irradiation

Arm Description

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 at a dose of 30 Gy in 10 daily fractions over 2 weeks

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
Overall Survival
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.
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.

Full Information

First Posted
November 17, 2009
Last Updated
March 25, 2013
Sponsor
Instituto Nacional de Cancerologia de Mexico
search

1. Study Identification

Unique Protocol Identification Number
NCT01015534
Brief Title
Whole Brain Radiotherapy With or Without Temozolomide at Daily Fixed-dose for Brain Metastases Treatment
Official Title
Phase II Randomized Study: Whole Brain Radiotherapy and Concomitant Temozolomide, Compared With Whole Brain Radiotherapy for Brain Metastases Treatment
Study Type
Interventional

2. Study Status

Record Verification Date
March 2013
Overall Recruitment Status
Completed
Study Start Date
January 2006 (undefined)
Primary Completion Date
October 2009 (Actual)
Study Completion Date
October 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Instituto Nacional de Cancerologia de Mexico

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Brain Neoplasms
Keywords
Brain metastases, Temozolomide, Whole-brain radiotherapy, Phase II trial

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
55 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Whole brain irradiation plus Temozolomide
Arm Type
Experimental
Arm Description
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.
Arm Title
Whole brain irradiation
Arm Type
Active Comparator
Arm Description
Whole brain irradiation at a dose of 30 Gy in 10 daily fractions over 2 weeks
Intervention Type
Drug
Intervention Name(s)
Temozolomide
Other Intervention Name(s)
Temodar, or, Temodal
Intervention Type
Radiation
Intervention Name(s)
Whole brain irradiation
Other Intervention Name(s)
Whole brain radiotherapy
Primary Outcome Measure Information:
Title
Objective Response Rates. Assessed With Cranial MRI
Description
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.
Time Frame
90 days
Secondary Outcome Measure Information:
Title
Survival Free of Brain Metastases Progression (PFS of BM)
Description
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.
Time Frame
at 90 days
Title
Overall Survival
Description
Overall survival:Time in months measured from treatment initiation until the date of death or the date of last follow-up.
Time Frame
1 year
Title
Number of Grade 3-4 Adverse Events (AE) That Are Definitely or Probably Related to Both Groups of Treatment.
Description
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.
Time Frame
4 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Carlos Gamboa-Vignolle, MD
Organizational Affiliation
Instituto Nacional de Cancerología de México
Official's Role
Principal Investigator
Facility Information:
Facility Name
Instituto Nacional de Cancerología de México
City
México
State/Province
D.F
ZIP/Postal Code
14080
Country
Mexico

12. IPD Sharing Statement

Citations:
PubMed Identifier
16134182
Citation
Jones SF, Greco FA, Gian VG, Miranda FT, Raefsky EL, Hainsworth JD, Willcutt NT, Beschorner AF, Kennerly G, Burris HA 3rd. A Phase I trial of protracted oral fixed-dose temozolomide. Cancer. 2005 Nov 1;104(9):1985-91. doi: 10.1002/cncr.21408.
Results Reference
background
PubMed Identifier
12202665
Citation
Antonadou D, Paraskevaidis M, Sarris G, Coliarakis N, Economou I, Karageorgis P, Throuvalas N. Phase II randomized trial of temozolomide and concurrent radiotherapy in patients with brain metastases. J Clin Oncol. 2002 Sep 1;20(17):3644-50. doi: 10.1200/JCO.2002.04.140.
Results Reference
background
PubMed Identifier
15629610
Citation
Verger E, Gil M, Yaya R, Vinolas N, Villa S, Pujol T, Quinto L, Graus F. Temozolomide and concomitant whole brain radiotherapy in patients with brain metastases: a phase II randomized trial. Int J Radiat Oncol Biol Phys. 2005 Jan 1;61(1):185-91. doi: 10.1016/j.ijrobp.2004.04.061.
Results Reference
background
PubMed Identifier
22257825
Citation
Gamboa-Vignolle C, Ferrari-Carballo T, Arrieta O, Mohar A. Whole-brain irradiation with concomitant daily fixed-dose temozolomide for brain metastases treatment: a randomised phase II trial. Radiother Oncol. 2012 Feb;102(2):187-91. doi: 10.1016/j.radonc.2011.12.004. Epub 2012 Jan 16.
Results Reference
derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs