Trial Outcomes & Findings for Safety and Tolerability of Low-Dose Temozolomide During Whole Brain Radiation in Patients With Cerebral Metastases From Non-Small-Cell Lung Cancer (Study P04071)(TERMINATED) (NCT NCT00266812)
NCT ID: NCT00266812
Last Updated: 2017-06-08
Results Overview
The occurrence of progression will be compared between the study groups by Kaplan-Meier curves. Responsiveness to temozolomide will be evaluated by brain Magnetic Resonance Imanging (MRI)/Computed Tomography (CT), thorax CT, and Quality of Life (QoL) assessments. Progression-free is defined as \<25% increase in tumor size on CT or MRI.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
35 participants
Primary outcome timeframe
6 months
Results posted on
2017-06-08
Participant Flow
Participant milestones
| Measure |
Chemotherapy With Temozolomide and Radiotherapy
Oral temozolomide 75mg/m2/day for 14 days, during radiation treatment, and later on temozolomide 100mg/m2/day at 14 days on/14 days off, until unacceptable toxicity or evidence of disease progression for up to 6 cycles from initial treatment. Radiotherapy (as in Intervention 2).
|
Radiotherapy Alone
2 regimens are allowed: a) 20 fractions of 2 Gray each, on days 1 to 5, 8 to 12, 15 to 19, and 22 to 26; b) 10 fractions of 3 Gray each, administered on days 1 to 5 and 8 to 12.
|
|---|---|---|
|
Overall Study
STARTED
|
22
|
13
|
|
Overall Study
COMPLETED
|
1
|
2
|
|
Overall Study
NOT COMPLETED
|
21
|
11
|
Reasons for withdrawal
| Measure |
Chemotherapy With Temozolomide and Radiotherapy
Oral temozolomide 75mg/m2/day for 14 days, during radiation treatment, and later on temozolomide 100mg/m2/day at 14 days on/14 days off, until unacceptable toxicity or evidence of disease progression for up to 6 cycles from initial treatment. Radiotherapy (as in Intervention 2).
|
Radiotherapy Alone
2 regimens are allowed: a) 20 fractions of 2 Gray each, on days 1 to 5, 8 to 12, 15 to 19, and 22 to 26; b) 10 fractions of 3 Gray each, administered on days 1 to 5 and 8 to 12.
|
|---|---|---|
|
Overall Study
Disease Progression
|
9
|
3
|
|
Overall Study
Death
|
5
|
4
|
|
Overall Study
Adverse Event
|
3
|
1
|
|
Overall Study
Protocol Violation
|
0
|
1
|
|
Overall Study
Withdrawal by Subject
|
0
|
2
|
|
Overall Study
Discontinued before starting study drug
|
4
|
0
|
Baseline Characteristics
Safety and Tolerability of Low-Dose Temozolomide During Whole Brain Radiation in Patients With Cerebral Metastases From Non-Small-Cell Lung Cancer (Study P04071)(TERMINATED)
Baseline characteristics by cohort
| Measure |
Chemotherapy With Temozolomide and Radiotherapy
n=22 Participants
Oral temozolomide 75mg/m2/day for 14 days, during radiation treatment, and later on temozolomide 100mg/m2/day at 14 days on/14 days off, until unacceptable toxicity or evidence of disease progression for up to 6 cycles from initial treatment. Radiotherapy (as in Intervention 2).
|
Radiotherapy Alone
n=13 Participants
2 regimens are allowed: a) 20 fractions of 2 Gray each, on days 1 to 5, 8 to 12, 15 to 19, and 22 to 26; b) 10 fractions of 3 Gray each, administered on days 1 to 5 and 8 to 12.
|
Total
n=35 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
65.12 years
STANDARD_DEVIATION 12.72 • n=5 Participants
|
63.02 years
STANDARD_DEVIATION 8.76 • n=7 Participants
|
64.3 years
STANDARD_DEVIATION 11.3 • n=5 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
13 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
21 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 6 monthsPopulation: Intent to treat (ITT) population (31 of the 35 patients enrolled; 4 participants discontinued prior to start of treatment) was analyzed.
The occurrence of progression will be compared between the study groups by Kaplan-Meier curves. Responsiveness to temozolomide will be evaluated by brain Magnetic Resonance Imanging (MRI)/Computed Tomography (CT), thorax CT, and Quality of Life (QoL) assessments. Progression-free is defined as \<25% increase in tumor size on CT or MRI.
Outcome measures
| Measure |
Chemotherapy With Temozolomide and Radiotherapy
n=18 Participants
Oral temozolomide 75mg/m2/day for 14 days, during radiation treatment, and later on temozolomide 100mg/m2/day at 14 days on/14 days off, until unacceptable toxicity or evidence of disease progression for up to 6 cycles from initial treatment. Radiotherapy (as in Intervention 2).
|
Radiotherapy Alone
n=13 Participants
2 regimens are allowed: a) 20 fractions of 2 Gray each, on days 1 to 5, 8 to 12, 15 to 19, and 22 to 26; b) 10 fractions of 3 Gray each, administered on days 1 to 5 and 8 to 12.
|
|---|---|---|
|
Number of Participants With Progression-free Survival (6 Month)
|
8 Participants
|
8 Participants
|
Adverse Events
Chemotherapy With Temozolomide and Radiotherapy
Serious events: 8 serious events
Other events: 15 other events
Deaths: 0 deaths
Radiotherapy Alone
Serious events: 4 serious events
Other events: 8 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Chemotherapy With Temozolomide and Radiotherapy
n=18 participants at risk
Oral temozolomide 75mg/m2/day for 14 days, during radiation treatment, and later on temozolomide 100mg/m2/day at 14 days on/14 days off, until unacceptable toxicity or evidence of disease progression for up to 6 cycles from initial treatment. Radiotherapy (as in Intervention 2).
|
Radiotherapy Alone
n=13 participants at risk
2 regimens are allowed: a) 20 fractions of 2 Gray each, on days 1 to 5, 8 to 12, 15 to 19, and 22 to 26; b) 10 fractions of 3 Gray each, administered on days 1 to 5 and 8 to 12.
|
|---|---|---|
|
Gastrointestinal disorders
DIARRHOEA
|
0.00%
0/18
|
7.7%
1/13 • Number of events 1
|
|
Gastrointestinal disorders
NAUSEA
|
5.6%
1/18 • Number of events 1
|
0.00%
0/13
|
|
Gastrointestinal disorders
VOMITING
|
5.6%
1/18 • Number of events 1
|
0.00%
0/13
|
|
General disorders
ASTHENIA
|
5.6%
1/18 • Number of events 1
|
0.00%
0/13
|
|
General disorders
DEATH
|
11.1%
2/18 • Number of events 2
|
7.7%
1/13 • Number of events 1
|
|
General disorders
GENERAL PHYSICAL HEALTH DETERIORATION
|
5.6%
1/18 • Number of events 1
|
0.00%
0/13
|
|
Infections and infestations
PNEUMONIA
|
5.6%
1/18 • Number of events 1
|
0.00%
0/13
|
|
Musculoskeletal and connective tissue disorders
BACK PAIN
|
5.6%
1/18 • Number of events 1
|
0.00%
0/13
|
|
Musculoskeletal and connective tissue disorders
PAIN IN EXTREMITY
|
5.6%
1/18 • Number of events 1
|
0.00%
0/13
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
NEOPLASM PROGRESSION
|
5.6%
1/18 • Number of events 1
|
0.00%
0/13
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
NEOPLASM RECURRENCE
|
5.6%
1/18 • Number of events 1
|
0.00%
0/13
|
|
Respiratory, thoracic and mediastinal disorders
HYDROPNEUMOTHORAX
|
5.6%
1/18 • Number of events 1
|
0.00%
0/13
|
|
Respiratory, thoracic and mediastinal disorders
RESPIRATORY FAILURE
|
0.00%
0/18
|
7.7%
1/13 • Number of events 1
|
|
Surgical and medical procedures
HOSPITALISATION
|
5.6%
1/18 • Number of events 1
|
7.7%
1/13 • Number of events 1
|
|
Vascular disorders
THROMBOSIS
|
5.6%
1/18 • Number of events 1
|
0.00%
0/13
|
Other adverse events
| Measure |
Chemotherapy With Temozolomide and Radiotherapy
n=18 participants at risk
Oral temozolomide 75mg/m2/day for 14 days, during radiation treatment, and later on temozolomide 100mg/m2/day at 14 days on/14 days off, until unacceptable toxicity or evidence of disease progression for up to 6 cycles from initial treatment. Radiotherapy (as in Intervention 2).
|
Radiotherapy Alone
n=13 participants at risk
2 regimens are allowed: a) 20 fractions of 2 Gray each, on days 1 to 5, 8 to 12, 15 to 19, and 22 to 26; b) 10 fractions of 3 Gray each, administered on days 1 to 5 and 8 to 12.
|
|---|---|---|
|
Blood and lymphatic system disorders
LEUKOPENIA
|
5.6%
1/18 • Number of events 1
|
0.00%
0/13
|
|
Blood and lymphatic system disorders
LYMPHOPENIA
|
5.6%
1/18 • Number of events 1
|
0.00%
0/13
|
|
Blood and lymphatic system disorders
THROMBOCYTOPENIA
|
5.6%
1/18 • Number of events 1
|
0.00%
0/13
|
|
Cardiac disorders
TACHYCARDIA
|
5.6%
1/18 • Number of events 1
|
0.00%
0/13
|
|
Ear and labyrinth disorders
VERTIGO
|
0.00%
0/18
|
7.7%
1/13 • Number of events 1
|
|
Gastrointestinal disorders
DIARRHOEA
|
5.6%
1/18 • Number of events 1
|
0.00%
0/13
|
|
Gastrointestinal disorders
NAUSEA
|
16.7%
3/18 • Number of events 3
|
0.00%
0/13
|
|
Gastrointestinal disorders
STOMATITIS
|
5.6%
1/18 • Number of events 1
|
0.00%
0/13
|
|
Gastrointestinal disorders
TOOTHACHE
|
5.6%
1/18 • Number of events 1
|
0.00%
0/13
|
|
Gastrointestinal disorders
VOMITING
|
16.7%
3/18 • Number of events 3
|
0.00%
0/13
|
|
General disorders
ASTHENIA
|
5.6%
1/18 • Number of events 1
|
0.00%
0/13
|
|
General disorders
CHEST PAIN
|
5.6%
1/18 • Number of events 2
|
0.00%
0/13
|
|
General disorders
DEATH
|
5.6%
1/18 • Number of events 1
|
7.7%
1/13 • Number of events 1
|
|
General disorders
FATIGUE
|
5.6%
1/18 • Number of events 1
|
0.00%
0/13
|
|
General disorders
GENERAL PHYSICAL HEALTH DETERIORATION
|
11.1%
2/18 • Number of events 2
|
0.00%
0/13
|
|
General disorders
PAIN
|
5.6%
1/18 • Number of events 1
|
0.00%
0/13
|
|
Infections and infestations
FEBRILE INFECTION
|
0.00%
0/18
|
7.7%
1/13 • Number of events 1
|
|
Infections and infestations
HERPES ZOSTER
|
5.6%
1/18 • Number of events 1
|
0.00%
0/13
|
|
Infections and infestations
ORAL CANDIDIASIS
|
5.6%
1/18 • Number of events 1
|
0.00%
0/13
|
|
Infections and infestations
PYODERMA
|
5.6%
1/18 • Number of events 1
|
0.00%
0/13
|
|
Infections and infestations
SEPSIS
|
5.6%
1/18 • Number of events 1
|
0.00%
0/13
|
|
Injury, poisoning and procedural complications
CONTUSION
|
5.6%
1/18 • Number of events 1
|
0.00%
0/13
|
|
Injury, poisoning and procedural complications
FALL
|
5.6%
1/18 • Number of events 1
|
0.00%
0/13
|
|
Investigations
WEIGHT DECREASED
|
5.6%
1/18 • Number of events 1
|
0.00%
0/13
|
|
Metabolism and nutrition disorders
ANOREXIA
|
0.00%
0/18
|
7.7%
1/13 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
ARTHRITIS
|
0.00%
0/18
|
7.7%
1/13 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
MUSCULAR WEAKNESS
|
5.6%
1/18 • Number of events 1
|
0.00%
0/13
|
|
Nervous system disorders
AGEUSIA
|
5.6%
1/18 • Number of events 1
|
0.00%
0/13
|
|
Nervous system disorders
COORDINATION ABNORMAL
|
5.6%
1/18 • Number of events 1
|
0.00%
0/13
|
|
Nervous system disorders
DEPRESSED LEVEL OF CONSCIOUSNESS
|
5.6%
1/18 • Number of events 2
|
0.00%
0/13
|
|
Nervous system disorders
DIZZINESS
|
5.6%
1/18 • Number of events 1
|
0.00%
0/13
|
|
Nervous system disorders
DYSGEUSIA
|
5.6%
1/18 • Number of events 1
|
0.00%
0/13
|
|
Nervous system disorders
MOTOR DYSFUNCTION
|
11.1%
2/18 • Number of events 2
|
0.00%
0/13
|
|
Nervous system disorders
PARAESTHESIA
|
5.6%
1/18 • Number of events 1
|
0.00%
0/13
|
|
Psychiatric disorders
CONFUSIONAL STATE
|
5.6%
1/18 • Number of events 2
|
0.00%
0/13
|
|
Psychiatric disorders
DEPRESSED MOOD
|
22.2%
4/18 • Number of events 4
|
7.7%
1/13 • Number of events 1
|
|
Psychiatric disorders
DEPRESSION
|
0.00%
0/18
|
15.4%
2/13 • Number of events 2
|
|
Psychiatric disorders
DYSSOMNIA
|
0.00%
0/18
|
7.7%
1/13 • Number of events 1
|
|
Psychiatric disorders
PERSONALITY CHANGE
|
5.6%
1/18 • Number of events 1
|
0.00%
0/13
|
|
Psychiatric disorders
SLEEP DISORDER
|
11.1%
2/18 • Number of events 2
|
7.7%
1/13 • Number of events 1
|
|
Renal and urinary disorders
INCONTINENCE
|
5.6%
1/18 • Number of events 1
|
0.00%
0/13
|
|
Respiratory, thoracic and mediastinal disorders
COUGH
|
5.6%
1/18 • Number of events 1
|
7.7%
1/13 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
DYSPNOEA
|
16.7%
3/18 • Number of events 3
|
7.7%
1/13 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
EPISTAXIS
|
0.00%
0/18
|
7.7%
1/13 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
PULMONARY EMBOLISM
|
5.6%
1/18 • Number of events 1
|
0.00%
0/13
|
|
Skin and subcutaneous tissue disorders
ALOPECIA
|
5.6%
1/18 • Number of events 1
|
7.7%
1/13 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
ECZEMA ASTEATOTIC
|
5.6%
1/18 • Number of events 1
|
0.00%
0/13
|
|
Skin and subcutaneous tissue disorders
ERYTHEMA
|
0.00%
0/18
|
7.7%
1/13 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
PRURITUS
|
0.00%
0/18
|
7.7%
1/13 • Number of events 1
|
|
Vascular disorders
CIRCULATORY COLLAPSE
|
0.00%
0/18
|
7.7%
1/13 • Number of events 1
|
|
Vascular disorders
DEEP VEIN THROMBOSIS
|
5.6%
1/18 • Number of events 1
|
0.00%
0/13
|
Additional Information
Senior Vice President, Global Clinical Development
Merck, Sharp & Dohme Corp
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER