Trial Outcomes & Findings for Whole-Brain Radiation Therapy and Pemetrexed in Treating Patients With Brain Metastases From Non-Small Cell Lung Cancer (NCT NCT00280748)
NCT ID: NCT00280748
Last Updated: 2017-06-23
Results Overview
Radiographic response will be measured by RECIST, Response Evaluation Criteria In Solid Tumors Criteria, indicating if subject experienced a Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), no response or less response than Partial or Progressive; or Progressive Disease (PD), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
TERMINATED
PHASE2
10 participants
126 days
2017-06-23
Participant Flow
Subjects were recruited from 2 institutions between May 2005 and April 2008.
Participant milestones
| Measure |
Single Arm Study
Single Arm Study
pemetrexed disodium: 500 mg/m2 once every 21 days up to 126 days
radiation therapy: Patients will receive cranial irradiation at 2.5 Gy per fraction, 5 days a week, for 3 weeks to a total dose of 37.5 Gy
|
|---|---|
|
Overall Study
STARTED
|
10
|
|
Overall Study
COMPLETED
|
6
|
|
Overall Study
NOT COMPLETED
|
4
|
Reasons for withdrawal
| Measure |
Single Arm Study
Single Arm Study
pemetrexed disodium: 500 mg/m2 once every 21 days up to 126 days
radiation therapy: Patients will receive cranial irradiation at 2.5 Gy per fraction, 5 days a week, for 3 weeks to a total dose of 37.5 Gy
|
|---|---|
|
Overall Study
Decline in performance
|
3
|
|
Overall Study
Extra-cranial disease progression
|
1
|
Baseline Characteristics
Whole-Brain Radiation Therapy and Pemetrexed in Treating Patients With Brain Metastases From Non-Small Cell Lung Cancer
Baseline characteristics by cohort
| Measure |
Single Arm Study
n=10 Participants
Single Arm Study
pemetrexed disodium: 500 mg/m2 once every 21 days up to 126 days
radiation therapy: Patients will receive cranial irradiation at 2.5 Gy per fraction, 5 days a week, for 3 weeks to a total dose of 37.5 Gy
|
|---|---|
|
Age, Continuous
|
62.5 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
8 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
10 participants
n=5 Participants
|
|
Karnofsky Performance Status
KPS 90-100; minor symptoms of disease
|
3 Participants
n=5 Participants
|
|
Karnofsky Performance Status
KPS 80-90; some symptoms of disease
|
0 Participants
n=5 Participants
|
|
Karnofsky Performance Status
KPS 70-80; unable to carry on all normal activity
|
6 Participants
n=5 Participants
|
|
Karnofsky Performance Status
KPS unknown
|
1 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 126 daysPopulation: Of the 10 patients, four patients were unevaluable due to extra-cranial disease progression or decline in performance status prevent re-evaluation.
Radiographic response will be measured by RECIST, Response Evaluation Criteria In Solid Tumors Criteria, indicating if subject experienced a Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), no response or less response than Partial or Progressive; or Progressive Disease (PD), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Outcome measures
| Measure |
Single Arm Study
n=6 Participants
Single Arm Study
pemetrexed disodium: 500 mg/m2 once every 21 days up to 126 days
radiation therapy: Patients will receive cranial irradiation at 2.5 Gy per fraction, 5 days a week, for 3 weeks to a total dose of 37.5 Gy
|
|---|---|
|
Response of Intracranial Metastases (Complete and Partial Response)
partial response
|
1 Participants
|
|
Response of Intracranial Metastases (Complete and Partial Response)
stable disease
|
3 Participants
|
|
Response of Intracranial Metastases (Complete and Partial Response)
progressive disease
|
2 Participants
|
SECONDARY outcome
Timeframe: maximum 5 monthsPopulation: All patients who received treatment were evaluated
Toxicities was assessed using Common Terminology Criteria for Adverse Events (CTCAE) grading scale. Only toxicities with attribution to chemotherapy of "definite" or "probable" are considered, as determined by treating physician.
Outcome measures
| Measure |
Single Arm Study
n=10 Participants
Single Arm Study
pemetrexed disodium: 500 mg/m2 once every 21 days up to 126 days
radiation therapy: Patients will receive cranial irradiation at 2.5 Gy per fraction, 5 days a week, for 3 weeks to a total dose of 37.5 Gy
|
|---|---|
|
Number of Subjects Experiencing Adverse Events
Acute bronchitis
|
1 Participants
|
|
Number of Subjects Experiencing Adverse Events
Blurred vision
|
1 Participants
|
|
Number of Subjects Experiencing Adverse Events
Dry skin
|
1 Participants
|
|
Number of Subjects Experiencing Adverse Events
Fatigue
|
2 Participants
|
|
Number of Subjects Experiencing Adverse Events
Anemia
|
2 Participants
|
|
Number of Subjects Experiencing Adverse Events
Alpecia
|
2 Participants
|
|
Number of Subjects Experiencing Adverse Events
Nausea
|
6 Participants
|
|
Number of Subjects Experiencing Adverse Events
Anorexia
|
1 Participants
|
|
Number of Subjects Experiencing Adverse Events
Pruritic rash on head
|
1 Participants
|
|
Number of Subjects Experiencing Adverse Events
Cramps
|
1 Participants
|
SECONDARY outcome
Timeframe: 4 yearsPopulation: Four patients were unevaluable due to extra-cranial disease progression or decline in performance status preventing re-evaluation.
Patients were followed for survival from start of treatment until death from any cause (up to 4 years)
Outcome measures
| Measure |
Single Arm Study
n=6 Participants
Single Arm Study
pemetrexed disodium: 500 mg/m2 once every 21 days up to 126 days
radiation therapy: Patients will receive cranial irradiation at 2.5 Gy per fraction, 5 days a week, for 3 weeks to a total dose of 37.5 Gy
|
|---|---|
|
Estimate the Overall Survival of Patients Treated With This Regimen.
|
6.0 months
Interval 1.7 to 8.3
|
SECONDARY outcome
Timeframe: baseline functional status onlyFunctional status evaluated using the Karnofsky functional status scale. The Karnofsky Performance Scale (KPS) Index allows patients to be classified as to their functional impairment. This can be used to compare effectiveness of different therapies and to assess the prognosis in individual patients. The lower the Karnofsky score, the worse the survival for most serious illnesses. The Karnofsky score runs from 100 to 0, where 100 is "perfect" health and 0 is death.
Outcome measures
| Measure |
Single Arm Study
n=10 Participants
Single Arm Study
pemetrexed disodium: 500 mg/m2 once every 21 days up to 126 days
radiation therapy: Patients will receive cranial irradiation at 2.5 Gy per fraction, 5 days a week, for 3 weeks to a total dose of 37.5 Gy
|
|---|---|
|
Evaluate the Functional Status of Patients Treated With This Regimen.
KPS 90-100; minor symptoms of disease
|
3 Participants
|
|
Evaluate the Functional Status of Patients Treated With This Regimen.
KPS 80-90; some symptoms of disease
|
0 Participants
|
|
Evaluate the Functional Status of Patients Treated With This Regimen.
KPS 70-80; unable to carry on all normal activity
|
6 Participants
|
|
Evaluate the Functional Status of Patients Treated With This Regimen.
KPS unknown
|
1 Participants
|
SECONDARY outcome
Timeframe: At Baseline, 30 days, and at end of treatment (maximum 5 months).Population: This study was terminated due to slow enrollment and the planned statistical analyses could not be performed due to limit sample size. The data represents the results of patients enrolled and treated on the trial.
A classification score defined as follows: 1. Able to work or to perform normal activities: neurological findings minor or absent 2. Able to carry out normal activities with minimal difficulties. Neurological impairment does not require nursing care or hospitalization 3. Seriously limited in performing normal activities. Requiring nursing care or hospitalization. Patients confined to bed or wheelchair or have significant intellectual impairment 4. Unable to perform even minimal normal activities. Requiring hospitalization and constant nursing care and feeding. Patients unable to communicate or in coma.A higher score indicates worse function.
Outcome measures
| Measure |
Single Arm Study
n=10 Participants
Single Arm Study
pemetrexed disodium: 500 mg/m2 once every 21 days up to 126 days
radiation therapy: Patients will receive cranial irradiation at 2.5 Gy per fraction, 5 days a week, for 3 weeks to a total dose of 37.5 Gy
|
|---|---|
|
Neurological Function by Radiation Oncology Group (RTOG) Neurological Function Classification
Pre-Treatment
|
1.6 scores on a scale
Interval 1.0 to 2.0
|
|
Neurological Function by Radiation Oncology Group (RTOG) Neurological Function Classification
Cycle 2
|
1.9 scores on a scale
Interval 1.0 to 3.0
|
|
Neurological Function by Radiation Oncology Group (RTOG) Neurological Function Classification
End of Treatment
|
2.2 scores on a scale
Interval 1.0 to 3.0
|
SECONDARY outcome
Timeframe: Baseline (pre-treatment), 30 days (Cycle 2 Day 1), and maximum 5 months (end of treatment).Population: This study was terminated due to slow enrollment and the planned statistical analyses could not be performed due to limited sample size. The data represents the results of patients enrolled and treated on the trial.
The Mini Mental State Examination is a 30-point questionnaire that is used to measure cognitive impairment. Score totals range from normal cognition (24-30 points), mild impairment (19-23 points), moderate impairment (10-18 points), to severe impairment (≤9 points).
Outcome measures
| Measure |
Single Arm Study
n=10 Participants
Single Arm Study
pemetrexed disodium: 500 mg/m2 once every 21 days up to 126 days
radiation therapy: Patients will receive cranial irradiation at 2.5 Gy per fraction, 5 days a week, for 3 weeks to a total dose of 37.5 Gy
|
|---|---|
|
Neurological Function by Mini Mental State Examination
Pre-Treatment
|
28 score on the scale
Interval 24.0 to 30.0
|
|
Neurological Function by Mini Mental State Examination
Cycle 2 Day 1
|
28.2 score on the scale
Interval 25.0 to 30.0
|
|
Neurological Function by Mini Mental State Examination
End of treatment
|
27.7 score on the scale
Interval 21.0 to 30.0
|
SECONDARY outcome
Timeframe: maximum 5 monthsPopulation: This study was terminated due to slow enrollment and the planned statistical analyses could not be performed due to limit sample size. The data represents the results of patients enrolled and treated on the trial.
Response was measured by Response Evaluation Criteria In Solid Tumors RECIST criteria v1.0. Complete Response (CR) - Disappearance of all lesions Partial Response (PR) - at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter. Stable Disease (SD) - neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum longest diameter since the treatment started. Progressive Disease (PD) - at least a 20% increase 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 lesions or unequivocal progression of existing nontarget lesions.
Outcome measures
| Measure |
Single Arm Study
n=10 Participants
Single Arm Study
pemetrexed disodium: 500 mg/m2 once every 21 days up to 126 days
radiation therapy: Patients will receive cranial irradiation at 2.5 Gy per fraction, 5 days a week, for 3 weeks to a total dose of 37.5 Gy
|
|---|---|
|
Response of Patients With Extracranial Disease Treated With Pemetrexed
partial response
|
2 Participants
|
|
Response of Patients With Extracranial Disease Treated With Pemetrexed
stable disease
|
3 Participants
|
|
Response of Patients With Extracranial Disease Treated With Pemetrexed
progressive disease
|
1 Participants
|
|
Response of Patients With Extracranial Disease Treated With Pemetrexed
missing data
|
4 Participants
|
Adverse Events
Single Arm Study
Serious adverse events
| Measure |
Single Arm Study
n=10 participants at risk
Single Arm Study
pemetrexed disodium: 500 mg/m2 once every 21 days up to 126 days
radiation therapy: Patients will receive cranial irradiation at 2.5 Gy per fraction, 5 days a week, for 3 weeks to a total dose of 37.5 Gy
|
|---|---|
|
Vascular disorders
pulmonary embolus
|
10.0%
1/10 • Number of events 1 • Adverse events were monitored up to 30 days after end of treatment
|
|
Nervous system disorders
Dizziness
|
10.0%
1/10 • Number of events 1 • Adverse events were monitored up to 30 days after end of treatment
|
|
Nervous system disorders
hallucinations
|
10.0%
1/10 • Number of events 1 • Adverse events were monitored up to 30 days after end of treatment
|
Other adverse events
| Measure |
Single Arm Study
n=10 participants at risk
Single Arm Study
pemetrexed disodium: 500 mg/m2 once every 21 days up to 126 days
radiation therapy: Patients will receive cranial irradiation at 2.5 Gy per fraction, 5 days a week, for 3 weeks to a total dose of 37.5 Gy
|
|---|---|
|
General disorders
Right maxillary pain with drainage
|
10.0%
1/10 • Number of events 1 • Adverse events were monitored up to 30 days after end of treatment
|
|
Blood and lymphatic system disorders
Anemia
|
20.0%
2/10 • Number of events 2 • Adverse events were monitored up to 30 days after end of treatment
|
|
Blood and lymphatic system disorders
face/upper/lower extremity swelling
|
10.0%
1/10 • Number of events 1 • Adverse events were monitored up to 30 days after end of treatment
|
|
Blood and lymphatic system disorders
swelling-lower extremities
|
10.0%
1/10 • Number of events 1 • Adverse events were monitored up to 30 days after end of treatment
|
|
Eye disorders
Blurred vision
|
10.0%
1/10 • Number of events 1 • Adverse events were monitored up to 30 days after end of treatment
|
|
Eye disorders
Dry Eyes
|
10.0%
1/10 • Number of events 1 • Adverse events were monitored up to 30 days after end of treatment
|
|
Gastrointestinal disorders
Anorexia
|
40.0%
4/10 • Number of events 4 • Adverse events were monitored up to 30 days after end of treatment
|
|
Gastrointestinal disorders
Constipation
|
20.0%
2/10 • Number of events 2 • Adverse events were monitored up to 30 days after end of treatment
|
|
Gastrointestinal disorders
Diarrhea
|
10.0%
1/10 • Number of events 1 • Adverse events were monitored up to 30 days after end of treatment
|
|
Gastrointestinal disorders
Flatulence
|
10.0%
1/10 • Number of events 1 • Adverse events were monitored up to 30 days after end of treatment
|
|
Gastrointestinal disorders
Hemmorroids
|
10.0%
1/10 • Number of events 1 • Adverse events were monitored up to 30 days after end of treatment
|
|
Gastrointestinal disorders
Mucositis
|
10.0%
1/10 • Number of events 1 • Adverse events were monitored up to 30 days after end of treatment
|
|
Gastrointestinal disorders
Nausea
|
80.0%
8/10 • Number of events 8 • Adverse events were monitored up to 30 days after end of treatment
|
|
Gastrointestinal disorders
Vomiting
|
10.0%
1/10 • Number of events 1 • Adverse events were monitored up to 30 days after end of treatment
|
|
General disorders
abdominal pain
|
10.0%
1/10 • Number of events 1 • Adverse events were monitored up to 30 days after end of treatment
|
|
General disorders
chest pain
|
10.0%
1/10 • Number of events 1 • Adverse events were monitored up to 30 days after end of treatment
|
|
General disorders
Headache
|
20.0%
2/10 • Number of events 2 • Adverse events were monitored up to 30 days after end of treatment
|
|
General disorders
Hip pain
|
10.0%
1/10 • Number of events 1 • Adverse events were monitored up to 30 days after end of treatment
|
|
General disorders
left lower quadrant pain
|
10.0%
1/10 • Number of events 1 • Adverse events were monitored up to 30 days after end of treatment
|
|
General disorders
Pain
|
10.0%
1/10 • Number of events 1 • Adverse events were monitored up to 30 days after end of treatment
|
|
General disorders
rib cage pain
|
10.0%
1/10 • Number of events 1 • Adverse events were monitored up to 30 days after end of treatment
|
|
General disorders
right foot 4th toes numbness
|
10.0%
1/10 • Number of events 1 • Adverse events were monitored up to 30 days after end of treatment
|
|
Infections and infestations
Acute bronchitis
|
10.0%
1/10 • Number of events 1 • Adverse events were monitored up to 30 days after end of treatment
|
|
Infections and infestations
UTI
|
10.0%
1/10 • Number of events 2 • Adverse events were monitored up to 30 days after end of treatment
|
|
Metabolism and nutrition disorders
difficulty sleeping
|
10.0%
1/10 • Number of events 1 • Adverse events were monitored up to 30 days after end of treatment
|
|
Metabolism and nutrition disorders
fatigue
|
20.0%
2/10 • Number of events 2 • Adverse events were monitored up to 30 days after end of treatment
|
|
Metabolism and nutrition disorders
Hypokalemia
|
10.0%
1/10 • Number of events 1 • Adverse events were monitored up to 30 days after end of treatment
|
|
Metabolism and nutrition disorders
Hyponatremia
|
10.0%
1/10 • Number of events 1 • Adverse events were monitored up to 30 days after end of treatment
|
|
Metabolism and nutrition disorders
weakness
|
20.0%
2/10 • Number of events 2 • Adverse events were monitored up to 30 days after end of treatment
|
|
Metabolism and nutrition disorders
weight loss
|
20.0%
2/10 • Number of events 2 • Adverse events were monitored up to 30 days after end of treatment
|
|
Musculoskeletal and connective tissue disorders
Cramps
|
10.0%
1/10 • Number of events 1 • Adverse events were monitored up to 30 days after end of treatment
|
|
Nervous system disorders
Anxiety
|
20.0%
2/10 • Number of events 2 • Adverse events were monitored up to 30 days after end of treatment
|
|
Nervous system disorders
Confusion
|
30.0%
3/10 • Number of events 3 • Adverse events were monitored up to 30 days after end of treatment
|
|
Nervous system disorders
depression
|
20.0%
2/10 • Number of events 2 • Adverse events were monitored up to 30 days after end of treatment
|
|
Nervous system disorders
Left eye visual disturbance
|
10.0%
1/10 • Number of events 1 • Adverse events were monitored up to 30 days after end of treatment
|
|
Nervous system disorders
memory impairment
|
10.0%
1/10 • Number of events 1 • Adverse events were monitored up to 30 days after end of treatment
|
|
Nervous system disorders
Transient ischemic attack
|
10.0%
1/10 • Number of events 1 • Adverse events were monitored up to 30 days after end of treatment
|
|
Renal and urinary disorders
Dysuria
|
10.0%
1/10 • Number of events 1 • Adverse events were monitored up to 30 days after end of treatment
|
|
Respiratory, thoracic and mediastinal disorders
cough
|
10.0%
1/10 • Number of events 1 • Adverse events were monitored up to 30 days after end of treatment
|
|
Respiratory, thoracic and mediastinal disorders
dyspnea
|
30.0%
3/10 • Number of events 3 • Adverse events were monitored up to 30 days after end of treatment
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
30.0%
3/10 • Number of events 3 • Adverse events were monitored up to 30 days after end of treatment
|
|
Skin and subcutaneous tissue disorders
dry skin
|
10.0%
1/10 • Number of events 1 • Adverse events were monitored up to 30 days after end of treatment
|
|
Skin and subcutaneous tissue disorders
Erythemic/vesicular papule-right temple
|
10.0%
1/10 • Number of events 1 • Adverse events were monitored up to 30 days after end of treatment
|
|
Skin and subcutaneous tissue disorders
insect bite
|
10.0%
1/10 • Number of events 1 • Adverse events were monitored up to 30 days after end of treatment
|
|
Skin and subcutaneous tissue disorders
pruritic rash on head
|
10.0%
1/10 • Number of events 1 • Adverse events were monitored up to 30 days after end of treatment
|
|
Vascular disorders
INR
|
10.0%
1/10 • Number of events 1 • Adverse events were monitored up to 30 days after end of treatment
|
|
Vascular disorders
Nosebleed
|
10.0%
1/10 • Number of events 1 • Adverse events were monitored up to 30 days after end of treatment
|
Additional Information
Robin V. Johnson
UNC Lineberger Comprehensive Cancer Center
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place