Trial Outcomes & Findings for Whole Brain Radiotherapy With or Without Temozolomide at Daily Fixed-dose for Brain Metastases Treatment (NCT NCT01015534)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

55 participants

Primary outcome timeframe

90 days

Results posted on

2013-05-08

Participant Flow

Participants were recruited from patients from Instituto Nacional de Cancerología de México, from January 2006 to September 2008.

Seventy-two patients were assessed for eligibility. Twelve patients did not meet inclusion criteria. Five patients declined to participate. Fifty-five patients were enrolled.

Participant milestones

Participant milestones
Measure	Whole Brain Irradiation and Temozolomide Whole brain irradiation, 1 fraction of 3 Gy x 5 days of each week for 2 weeks, Monday to Friday and a fixed dose of oral temozolomide, 1h before each daily fraction of Whole brain irradiation, 200 mg on Monday, Wednesday, Friday; 300 mg on Tuesday, and Thursday. Without extra cycles of Temozolomide.	Whole Brain Irradiation Whole brain irradiation, 1 fraction of 3 Gy x 5 days each week for 2 weeks, Monday to Friday.
Overall Study STARTED	28	27
Overall Study COMPLETED	27	27
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Whole Brain Irradiation and Temozolomide n=28 Participants Whole brain irradiation, 1 fraction of 3 Gy x 5 days of each week for 2 weeks, Monday to Friday and a fixed dose of oral temozolomide, 1h before each daily fraction of Whole brain irradiation, 200 mg on Monday, Wednesday, Friday; 300 mg on Tuesday, and Thursday. Without extra cycles of Temozolomide.	Whole Brain Irradiation n=27 Participants Whole brain irradiation, 1 fraction of 3 Gy x 5 days each week for 2 weeks, Monday to Friday.	Total n=55 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	25 Participants n=5 Participants	19 Participants n=7 Participants	44 Participants n=5 Participants
Age, Categorical >=65 years	3 Participants n=5 Participants	8 Participants n=7 Participants	11 Participants n=5 Participants
Age Continuous	49.5 years STANDARD_DEVIATION 13.4 • n=5 Participants	53.8 years STANDARD_DEVIATION 13.7 • n=7 Participants	51.7 years STANDARD_DEVIATION 13.55 • n=5 Participants
Sex: Female, Male Female	25 Participants n=5 Participants	22 Participants n=7 Participants	47 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants
Region of Enrollment Mexico	28 participants n=5 Participants	27 participants n=7 Participants	55 participants n=5 Participants

PRIMARY outcome

Timeframe: 90 days

Population: Data on all enrolled participants were included in an intention-to-treat analysis.

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.

Outcome measures

Outcome measures
Measure	Whole Brain Irradiation n=27 Participants Whole brain irradiation, at a dose of 30 Gy in 10 daily fractions over 2 weeks	Whole Brain Irradiation and Temozolomide n=28 Participants 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.
Objective Response Rates. Assessed With Cranial MRI	48.1 Percentage of participants with OR Interval 29.2 to 66.9	78.6 Percentage of participants with OR Interval 63.4 to 93.8

SECONDARY outcome

Timeframe: at 90 days

Population: Data on all enrolled participants were included in an intention-to-treat analysis.

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.

Outcome measures

Outcome measures
Measure	Whole Brain Irradiation n=27 Participants Whole brain irradiation, at a dose of 30 Gy in 10 daily fractions over 2 weeks	Whole Brain Irradiation and Temozolomide n=28 Participants 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.
Survival Free of Brain Metastases Progression (PFS of BM)	83.7 Percentage of Participants Interval 69.0 to 98.4	88.7 Percentage of Participants Interval 76.7 to 100.0

SECONDARY outcome

Timeframe: 1 year

Population: Data on all enrolled participants were included in an intention-to-treat analysis.

Overall survival:Time in months measured from treatment initiation until the date of death or the date of last follow-up.

Outcome measures

Outcome measures
Measure	Whole Brain Irradiation n=27 Participants Whole brain irradiation, at a dose of 30 Gy in 10 daily fractions over 2 weeks	Whole Brain Irradiation and Temozolomide n=28 Participants 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.
Overall Survival	8.1 Months of Overall Survival Interval 5.9 to 10.1	8 Months of Overall Survival Interval 4.9 to 11.1

SECONDARY outcome

Timeframe: 4 months

Population: Participants were assessed with a Complete blood count at the end of the first and second weeks of treatment. A standard biochemical profile was performed at the end of the second week of treatment, at 2 weeks after completion and at 2 months thereafter. Participants also were evaluated clinically with the same periodicity .

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.

Outcome measures

Outcome measures
Measure	Whole Brain Irradiation n=27 Participants Whole brain irradiation, at a dose of 30 Gy in 10 daily fractions over 2 weeks	Whole Brain Irradiation and Temozolomide n=28 Participants 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.
Number of Grade 3-4 Adverse Events (AE) That Are Definitely or Probably Related to Both Groups of Treatment. Leukopenia	0 Events	1 Events
Number of Grade 3-4 Adverse Events (AE) That Are Definitely or Probably Related to Both Groups of Treatment. Lymphopenia	6 Events	11 Events
Number of Grade 3-4 Adverse Events (AE) That Are Definitely or Probably Related to Both Groups of Treatment. Nausea-Vomiting	0 Events	1 Events
Number of Grade 3-4 Adverse Events (AE) That Are Definitely or Probably Related to Both Groups of Treatment. Neutropenia	1 Events	1 Events
Number of Grade 3-4 Adverse Events (AE) That Are Definitely or Probably Related to Both Groups of Treatment. Platelets	0 Events	3 Events

Adverse Events

Whole Brain Irradiation and Temozolomide

Serious events: 17 serious events

Other events: 11 other events

Deaths: 0 deaths

Whole Brain Irradiation

Serious events: 7 serious events

Other events: 13 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Whole Brain Irradiation and Temozolomide n=28 participants at risk Whole brain irradiation, 1 fraction of 3 Gy x 5 days of each week for 2 weeks, Monday to Friday and a fixed dose of oral temozolomide, 1h before each daily fraction of Whole brain irradiation, 200 mg on Monday, Wednesday, Friday; 300 mg on Tuesday, and Thursday. Without extra cycles of Temozolomide.	Whole Brain Irradiation n=27 participants at risk Whole brain irradiation, 1 fraction of 3 Gy x 5 days each week for 2 weeks, Monday to Friday.
Blood and lymphatic system disorders Lymphopenia	39.3% 11/28 • Number of events 11 • 3 months Patients were assessed as follows: with a Complete blood count at the end of the first and second week of treatment. A standard biochemical profile at the end of the second week of treatment, at 2 weeks after completion and at 2 months thereafter. Also were evaluated clinically with the same periodicity.	22.2% 6/27 • Number of events 6 • 3 months Patients were assessed as follows: with a Complete blood count at the end of the first and second week of treatment. A standard biochemical profile at the end of the second week of treatment, at 2 weeks after completion and at 2 months thereafter. Also were evaluated clinically with the same periodicity.
Blood and lymphatic system disorders Leukopenia	3.6% 1/28 • Number of events 1 • 3 months Patients were assessed as follows: with a Complete blood count at the end of the first and second week of treatment. A standard biochemical profile at the end of the second week of treatment, at 2 weeks after completion and at 2 months thereafter. Also were evaluated clinically with the same periodicity.	0.00% 0/27 • 3 months Patients were assessed as follows: with a Complete blood count at the end of the first and second week of treatment. A standard biochemical profile at the end of the second week of treatment, at 2 weeks after completion and at 2 months thereafter. Also were evaluated clinically with the same periodicity.
Blood and lymphatic system disorders Platelets	10.7% 3/28 • Number of events 3 • 3 months Patients were assessed as follows: with a Complete blood count at the end of the first and second week of treatment. A standard biochemical profile at the end of the second week of treatment, at 2 weeks after completion and at 2 months thereafter. Also were evaluated clinically with the same periodicity.	0.00% 0/27 • 3 months Patients were assessed as follows: with a Complete blood count at the end of the first and second week of treatment. A standard biochemical profile at the end of the second week of treatment, at 2 weeks after completion and at 2 months thereafter. Also were evaluated clinically with the same periodicity.
Blood and lymphatic system disorders Neutrophils	3.6% 1/28 • Number of events 1 • 3 months Patients were assessed as follows: with a Complete blood count at the end of the first and second week of treatment. A standard biochemical profile at the end of the second week of treatment, at 2 weeks after completion and at 2 months thereafter. Also were evaluated clinically with the same periodicity.	3.7% 1/27 • Number of events 1 • 3 months Patients were assessed as follows: with a Complete blood count at the end of the first and second week of treatment. A standard biochemical profile at the end of the second week of treatment, at 2 weeks after completion and at 2 months thereafter. Also were evaluated clinically with the same periodicity.
Hepatobiliary disorders Nausea-Vomiting	3.6% 1/28 • Number of events 1 • 3 months Patients were assessed as follows: with a Complete blood count at the end of the first and second week of treatment. A standard biochemical profile at the end of the second week of treatment, at 2 weeks after completion and at 2 months thereafter. Also were evaluated clinically with the same periodicity.	0.00% 0/27 • 3 months Patients were assessed as follows: with a Complete blood count at the end of the first and second week of treatment. A standard biochemical profile at the end of the second week of treatment, at 2 weeks after completion and at 2 months thereafter. Also were evaluated clinically with the same periodicity.

Other adverse events

Other adverse events
Measure	Whole Brain Irradiation and Temozolomide n=28 participants at risk Whole brain irradiation, 1 fraction of 3 Gy x 5 days of each week for 2 weeks, Monday to Friday and a fixed dose of oral temozolomide, 1h before each daily fraction of Whole brain irradiation, 200 mg on Monday, Wednesday, Friday; 300 mg on Tuesday, and Thursday. Without extra cycles of Temozolomide.	Whole Brain Irradiation n=27 participants at risk Whole brain irradiation, 1 fraction of 3 Gy x 5 days each week for 2 weeks, Monday to Friday.
Blood and lymphatic system disorders Lymphopenia	17.9% 5/28 • Number of events 5 • 3 months Patients were assessed as follows: with a Complete blood count at the end of the first and second week of treatment. A standard biochemical profile at the end of the second week of treatment, at 2 weeks after completion and at 2 months thereafter. Also were evaluated clinically with the same periodicity.	40.7% 11/27 • Number of events 11 • 3 months Patients were assessed as follows: with a Complete blood count at the end of the first and second week of treatment. A standard biochemical profile at the end of the second week of treatment, at 2 weeks after completion and at 2 months thereafter. Also were evaluated clinically with the same periodicity.
Blood and lymphatic system disorders platelets	10.7% 3/28 • Number of events 3 • 3 months Patients were assessed as follows: with a Complete blood count at the end of the first and second week of treatment. A standard biochemical profile at the end of the second week of treatment, at 2 weeks after completion and at 2 months thereafter. Also were evaluated clinically with the same periodicity.	3.7% 1/27 • Number of events 1 • 3 months Patients were assessed as follows: with a Complete blood count at the end of the first and second week of treatment. A standard biochemical profile at the end of the second week of treatment, at 2 weeks after completion and at 2 months thereafter. Also were evaluated clinically with the same periodicity.
Metabolism and nutrition disorders Alanine aminotransferase - Aspartate aminotransferase	10.7% 3/28 • Number of events 3 • 3 months Patients were assessed as follows: with a Complete blood count at the end of the first and second week of treatment. A standard biochemical profile at the end of the second week of treatment, at 2 weeks after completion and at 2 months thereafter. Also were evaluated clinically with the same periodicity.	3.7% 1/27 • Number of events 1 • 3 months Patients were assessed as follows: with a Complete blood count at the end of the first and second week of treatment. A standard biochemical profile at the end of the second week of treatment, at 2 weeks after completion and at 2 months thereafter. Also were evaluated clinically with the same periodicity.

Additional Information

Carlos Gamboa Vignolle/ Radiation Oncologist

Instituto Nacional de Cancerologia de Mexico

Phone: 0155556280400

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place