Trial Outcomes & Findings for Irinotecan and Temozolomide in Treating Patients With Breast Cancer Who Have Received Previous Treatment for Brain Metastases (NCT NCT00617539)
NCT ID: NCT00617539
Last Updated: 2018-04-20
Results Overview
Imaging was performed at 8-week intervals to assess response to treatment. Patients with known or suspected leptomeningeal disease were deemed to have a complete response if CSF cytology converted to negative (if positive at baseline) and all meningeal enhancement or nodularity of brain and/or spine MRI resolved. A modified RECIST 1.0 criteria was used to assess CNS response for patients with new or progressing brain metastases. In this modified RECIST criteria, CNS lesions \<1cm were not considered measurable, but were considered evaluable for response and progression. Progressive disease for patients with lesions \<1 cm was defined as follows: growth of a lesion from less than or equal to 5 mm to greater than or equal to 10mm; or, growth of a 6-9 mm lesion by at least 5 mm in the case of non-target parenchymal brain metastases.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
30 participants
Primary outcome timeframe
Baseline scan prior to study entry was performed within 14 days of cycle 1 day 1, then every 8 weeks from then until disease progression or up to 2 years
Results posted on
2018-04-20
Participant Flow
Participant milestones
| Measure |
Irinotecan and Temozolomide
125 mg/m\^2 irinotecan hydrochloride administered intravenously on days 1 and 15 of a 28 day cycle
100 mg/m\^2 temozolomide orally for seven days on days 1-7 and days 15-21 of a 28 day cycle
|
|---|---|
|
Overall Study
STARTED
|
30
|
|
Overall Study
COMPLETED
|
30
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Irinotecan and Temozolomide in Treating Patients With Breast Cancer Who Have Received Previous Treatment for Brain Metastases
Baseline characteristics by cohort
| Measure |
Irinotecan and Temozolomide
n=30 Participants
125 mg/m\^2 irinotecan hydrochloride administered intravenously on days 1 and 15 of a 28 day cycle 100 mg/m\^2 temozolomide orally for seven days on days 1-7 and days 15-21 of a 28 day cycle
|
|---|---|
|
Age, Continuous
|
53.5 years
n=93 Participants
|
|
Sex: Female, Male
Female
|
30 Participants
n=93 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=93 Participants
|
|
Region of Enrollment
United States
|
30 Participants
n=93 Participants
|
PRIMARY outcome
Timeframe: Baseline scan prior to study entry was performed within 14 days of cycle 1 day 1, then every 8 weeks from then until disease progression or up to 2 yearsImaging was performed at 8-week intervals to assess response to treatment. Patients with known or suspected leptomeningeal disease were deemed to have a complete response if CSF cytology converted to negative (if positive at baseline) and all meningeal enhancement or nodularity of brain and/or spine MRI resolved. A modified RECIST 1.0 criteria was used to assess CNS response for patients with new or progressing brain metastases. In this modified RECIST criteria, CNS lesions \<1cm were not considered measurable, but were considered evaluable for response and progression. Progressive disease for patients with lesions \<1 cm was defined as follows: growth of a lesion from less than or equal to 5 mm to greater than or equal to 10mm; or, growth of a 6-9 mm lesion by at least 5 mm in the case of non-target parenchymal brain metastases.
Outcome measures
| Measure |
Irinotecan and Temozolomide
n=30 Participants
irinotecan hydrochloride administered intravenously (IV) at a starting dose of 125 mg/m2 on days 1 and 15 of a 28 day cycle
temozolomide orally for seven days at a starting dose of 100 mg/m2 on days 1-7 and days 15-21 of a 28 day cycle
|
|---|---|
|
Number of Patients With Objective Treatment Response (Complete or Partial) in the CNS
|
2 Participants
|
PRIMARY outcome
Timeframe: From 1 day 1 (first day of treatment) every 8 weeks until scan shows disease progression or up to 2 yearsThe number of patients experiencing a clinical benefit is the sum of patients with an objective response plus patients with stable disease at ≥ 16 weeks from cycle 1 day 1 (first day of treatment). If a patient did not come back for a follow up scan after clinical deterioration, then they were only considered stable up to the time of the last scan they had per protocol.
Outcome measures
| Measure |
Irinotecan and Temozolomide
n=30 Participants
irinotecan hydrochloride administered intravenously (IV) at a starting dose of 125 mg/m2 on days 1 and 15 of a 28 day cycle
temozolomide orally for seven days at a starting dose of 100 mg/m2 on days 1-7 and days 15-21 of a 28 day cycle
|
|---|---|
|
Number of Patients Experiencing a Clinical Benefit
|
7 Participants
|
SECONDARY outcome
Timeframe: Baseline scan prior to study entry was performed within 14 days of cycle 1 day 1, then every 8 weeks from then until disease progression or up to 2 yearsImaging at 8-week intervals to assess response to treatment. A modified RECIST 1.0 criteria was used to assess response and time to progression in the CNS for patients with progressing brain metastases. In this modified RECIST criteria, CNS lesions \<1cm were not considered measurable, but were considered evaluable for response and progression. Progressive disease for patients with lesions \<1 cm was defined as follows: growth of a lesion from less than or equal to 5 mm to greater than or equal to 10mm; or, growth of a 6-9 mm lesion by at least 5 mm in the case of non-target parenchymal brain metastases. If patient did not come back for a follow up scan after clinical deterioration, patient was only considered stable up to the time of the last scan per protocol and time to progression would be from cycle 1 day 1 to the last scan they completed that was stable.
Outcome measures
| Measure |
Irinotecan and Temozolomide
n=30 Participants
irinotecan hydrochloride administered intravenously (IV) at a starting dose of 125 mg/m2 on days 1 and 15 of a 28 day cycle
temozolomide orally for seven days at a starting dose of 100 mg/m2 on days 1-7 and days 15-21 of a 28 day cycle
|
|---|---|
|
Time to First Progression in CNS
|
70 Days
Interval 13.0 to 444.0
|
SECONDARY outcome
Timeframe: Time from initiation of study participation until death or up to 3 yearsTime from initiation of study participation until death
Outcome measures
| Measure |
Irinotecan and Temozolomide
n=30 Participants
irinotecan hydrochloride administered intravenously (IV) at a starting dose of 125 mg/m2 on days 1 and 15 of a 28 day cycle
temozolomide orally for seven days at a starting dose of 100 mg/m2 on days 1-7 and days 15-21 of a 28 day cycle
|
|---|---|
|
Overall Time of Survival
|
146 Days
Interval 20.0 to 1043.0
|
SECONDARY outcome
Timeframe: CTCs drawn on cycle 1 day 1, collection at 8 week intervals on patients who did not progress on their 8 week scans up to 2 yearsPopulation: Of 20 patients with CTCs measured at baseline, 14 were also measured at 8 weeks
CTCs were measured in blood using the Cellsearch(R) assay in 14 of the 20 patients measured at baseline
Outcome measures
| Measure |
Irinotecan and Temozolomide
n=14 Participants
irinotecan hydrochloride administered intravenously (IV) at a starting dose of 125 mg/m2 on days 1 and 15 of a 28 day cycle
temozolomide orally for seven days at a starting dose of 100 mg/m2 on days 1-7 and days 15-21 of a 28 day cycle
|
|---|---|
|
Number of Patients Whose Circulating Tumor Cells (CTCs) Decreased From >5 to <5 CTCs Per 7.5 mL
|
1 participants
|
Adverse Events
Irinotecan and Temozolomide
Serious events: 16 serious events
Other events: 30 other events
Deaths: 14 deaths
Serious adverse events
| Measure |
Irinotecan and Temozolomide
n=30 participants at risk
irinotecan hydrochloride administered intravenously at a starting dose of 125 mg/m2 on days 1 and 15 of a 28 day cycle, and temozolomide orally for seven days at a starting dose of 100 mg/m2 on days 1-7 and days 15-21 every 28 days.
|
|---|---|
|
Infections and infestations
Infection
|
13.3%
4/30 • During study treatment (up to 3 years)
Only one mortality during study treatment window. All other mortalities occured during the long term follow up and are not reported in the All-Cause Mortality module.
|
|
Renal and urinary disorders
Hyponatremia
|
13.3%
4/30 • During study treatment (up to 3 years)
Only one mortality during study treatment window. All other mortalities occured during the long term follow up and are not reported in the All-Cause Mortality module.
|
|
General disorders
Fatigue
|
10.0%
3/30 • During study treatment (up to 3 years)
Only one mortality during study treatment window. All other mortalities occured during the long term follow up and are not reported in the All-Cause Mortality module.
|
|
Gastrointestinal disorders
Vomiting
|
6.7%
2/30 • During study treatment (up to 3 years)
Only one mortality during study treatment window. All other mortalities occured during the long term follow up and are not reported in the All-Cause Mortality module.
|
|
Gastrointestinal disorders
Nausea
|
3.3%
1/30 • During study treatment (up to 3 years)
Only one mortality during study treatment window. All other mortalities occured during the long term follow up and are not reported in the All-Cause Mortality module.
|
|
Gastrointestinal disorders
Diarrhea
|
3.3%
1/30 • During study treatment (up to 3 years)
Only one mortality during study treatment window. All other mortalities occured during the long term follow up and are not reported in the All-Cause Mortality module.
|
|
Hepatobiliary disorders
Transaminitis
|
3.3%
1/30 • During study treatment (up to 3 years)
Only one mortality during study treatment window. All other mortalities occured during the long term follow up and are not reported in the All-Cause Mortality module.
|
|
Nervous system disorders
Neuropathy
|
3.3%
1/30 • During study treatment (up to 3 years)
Only one mortality during study treatment window. All other mortalities occured during the long term follow up and are not reported in the All-Cause Mortality module.
|
|
Blood and lymphatic system disorders
Lymphopenia
|
53.3%
16/30 • During study treatment (up to 3 years)
Only one mortality during study treatment window. All other mortalities occured during the long term follow up and are not reported in the All-Cause Mortality module.
|
|
Blood and lymphatic system disorders
Leukopenia
|
16.7%
5/30 • During study treatment (up to 3 years)
Only one mortality during study treatment window. All other mortalities occured during the long term follow up and are not reported in the All-Cause Mortality module.
|
|
Blood and lymphatic system disorders
Neutropenia
|
16.7%
5/30 • During study treatment (up to 3 years)
Only one mortality during study treatment window. All other mortalities occured during the long term follow up and are not reported in the All-Cause Mortality module.
|
|
Blood and lymphatic system disorders
Anemia
|
10.0%
3/30 • During study treatment (up to 3 years)
Only one mortality during study treatment window. All other mortalities occured during the long term follow up and are not reported in the All-Cause Mortality module.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
10.0%
3/30 • During study treatment (up to 3 years)
Only one mortality during study treatment window. All other mortalities occured during the long term follow up and are not reported in the All-Cause Mortality module.
|
|
General disorders
Dehydration
|
6.7%
2/30 • During study treatment (up to 3 years)
Only one mortality during study treatment window. All other mortalities occured during the long term follow up and are not reported in the All-Cause Mortality module.
|
|
General disorders
Alkaline phosphatase increased
|
3.3%
1/30 • During study treatment (up to 3 years)
Only one mortality during study treatment window. All other mortalities occured during the long term follow up and are not reported in the All-Cause Mortality module.
|
|
Nervous system disorders
Mental status change
|
3.3%
1/30 • During study treatment (up to 3 years)
Only one mortality during study treatment window. All other mortalities occured during the long term follow up and are not reported in the All-Cause Mortality module.
|
|
Gastrointestinal disorders
Dysphagia
|
3.3%
1/30 • During study treatment (up to 3 years)
Only one mortality during study treatment window. All other mortalities occured during the long term follow up and are not reported in the All-Cause Mortality module.
|
|
General disorders
Weakness
|
3.3%
1/30 • During study treatment (up to 3 years)
Only one mortality during study treatment window. All other mortalities occured during the long term follow up and are not reported in the All-Cause Mortality module.
|
Other adverse events
| Measure |
Irinotecan and Temozolomide
n=30 participants at risk
irinotecan hydrochloride administered intravenously at a starting dose of 125 mg/m2 on days 1 and 15 of a 28 day cycle, and temozolomide orally for seven days at a starting dose of 100 mg/m2 on days 1-7 and days 15-21 every 28 days.
|
|---|---|
|
Infections and infestations
Infection
|
16.7%
5/30 • During study treatment (up to 3 years)
Only one mortality during study treatment window. All other mortalities occured during the long term follow up and are not reported in the All-Cause Mortality module.
|
|
Renal and urinary disorders
Hyponatremia
|
3.3%
1/30 • During study treatment (up to 3 years)
Only one mortality during study treatment window. All other mortalities occured during the long term follow up and are not reported in the All-Cause Mortality module.
|
|
General disorders
Fatigue
|
50.0%
15/30 • During study treatment (up to 3 years)
Only one mortality during study treatment window. All other mortalities occured during the long term follow up and are not reported in the All-Cause Mortality module.
|
|
Gastrointestinal disorders
Vomiting
|
50.0%
15/30 • During study treatment (up to 3 years)
Only one mortality during study treatment window. All other mortalities occured during the long term follow up and are not reported in the All-Cause Mortality module.
|
|
Gastrointestinal disorders
Nausea
|
73.3%
22/30 • During study treatment (up to 3 years)
Only one mortality during study treatment window. All other mortalities occured during the long term follow up and are not reported in the All-Cause Mortality module.
|
|
Gastrointestinal disorders
Diarrhea
|
50.0%
15/30 • During study treatment (up to 3 years)
Only one mortality during study treatment window. All other mortalities occured during the long term follow up and are not reported in the All-Cause Mortality module.
|
|
Hepatobiliary disorders
Transaminitis
|
16.7%
5/30 • During study treatment (up to 3 years)
Only one mortality during study treatment window. All other mortalities occured during the long term follow up and are not reported in the All-Cause Mortality module.
|
|
Nervous system disorders
Neuropathy
|
23.3%
7/30 • During study treatment (up to 3 years)
Only one mortality during study treatment window. All other mortalities occured during the long term follow up and are not reported in the All-Cause Mortality module.
|
|
Endocrine disorders
Hypocalcemia
|
26.7%
8/30 • During study treatment (up to 3 years)
Only one mortality during study treatment window. All other mortalities occured during the long term follow up and are not reported in the All-Cause Mortality module.
|
|
Gastrointestinal disorders
Mucositis
|
26.7%
8/30 • During study treatment (up to 3 years)
Only one mortality during study treatment window. All other mortalities occured during the long term follow up and are not reported in the All-Cause Mortality module.
|
|
Gastrointestinal disorders
Constipation
|
26.7%
8/30 • During study treatment (up to 3 years)
Only one mortality during study treatment window. All other mortalities occured during the long term follow up and are not reported in the All-Cause Mortality module.
|
|
Renal and urinary disorders
Hypokalemia
|
20.0%
6/30 • During study treatment (up to 3 years)
Only one mortality during study treatment window. All other mortalities occured during the long term follow up and are not reported in the All-Cause Mortality module.
|
|
General disorders
Anorexia
|
20.0%
6/30 • During study treatment (up to 3 years)
Only one mortality during study treatment window. All other mortalities occured during the long term follow up and are not reported in the All-Cause Mortality module.
|
|
Nervous system disorders
Dizziness
|
16.7%
5/30 • During study treatment (up to 3 years)
Only one mortality during study treatment window. All other mortalities occured during the long term follow up and are not reported in the All-Cause Mortality module.
|
|
Skin and subcutaneous tissue disorders
Rash
|
30.0%
9/30 • During study treatment (up to 3 years)
Only one mortality during study treatment window. All other mortalities occured during the long term follow up and are not reported in the All-Cause Mortality module.
|
|
Gastrointestinal disorders
Dyspepsia
|
20.0%
6/30 • During study treatment (up to 3 years)
Only one mortality during study treatment window. All other mortalities occured during the long term follow up and are not reported in the All-Cause Mortality module.
|
|
Blood and lymphatic system disorders
Lymphopenia
|
16.7%
5/30 • During study treatment (up to 3 years)
Only one mortality during study treatment window. All other mortalities occured during the long term follow up and are not reported in the All-Cause Mortality module.
|
|
Blood and lymphatic system disorders
Leukopenia
|
23.3%
7/30 • During study treatment (up to 3 years)
Only one mortality during study treatment window. All other mortalities occured during the long term follow up and are not reported in the All-Cause Mortality module.
|
|
Blood and lymphatic system disorders
Neutropenia
|
26.7%
8/30 • During study treatment (up to 3 years)
Only one mortality during study treatment window. All other mortalities occured during the long term follow up and are not reported in the All-Cause Mortality module.
|
|
Blood and lymphatic system disorders
Anemia
|
46.7%
14/30 • During study treatment (up to 3 years)
Only one mortality during study treatment window. All other mortalities occured during the long term follow up and are not reported in the All-Cause Mortality module.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
23.3%
7/30 • During study treatment (up to 3 years)
Only one mortality during study treatment window. All other mortalities occured during the long term follow up and are not reported in the All-Cause Mortality module.
|
|
General disorders
Dehydration
|
10.0%
3/30 • During study treatment (up to 3 years)
Only one mortality during study treatment window. All other mortalities occured during the long term follow up and are not reported in the All-Cause Mortality module.
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
13.3%
4/30 • During study treatment (up to 3 years)
Only one mortality during study treatment window. All other mortalities occured during the long term follow up and are not reported in the All-Cause Mortality module.
|
|
General disorders
Fever
|
10.0%
3/30 • During study treatment (up to 3 years)
Only one mortality during study treatment window. All other mortalities occured during the long term follow up and are not reported in the All-Cause Mortality module.
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
10.0%
3/30 • During study treatment (up to 3 years)
Only one mortality during study treatment window. All other mortalities occured during the long term follow up and are not reported in the All-Cause Mortality module.
|
|
Hepatobiliary disorders
Hyperbilirubinemia
|
10.0%
3/30 • During study treatment (up to 3 years)
Only one mortality during study treatment window. All other mortalities occured during the long term follow up and are not reported in the All-Cause Mortality module.
|
|
Metabolism and nutrition disorders
Alkaline phosphatase increased
|
6.7%
2/30 • During study treatment (up to 3 years)
Only one mortality during study treatment window. All other mortalities occured during the long term follow up and are not reported in the All-Cause Mortality module.
|
|
General disorders
Weakness
|
6.7%
2/30 • During study treatment (up to 3 years)
Only one mortality during study treatment window. All other mortalities occured during the long term follow up and are not reported in the All-Cause Mortality module.
|
|
Gastrointestinal disorders
Xerostomia
|
6.7%
2/30 • During study treatment (up to 3 years)
Only one mortality during study treatment window. All other mortalities occured during the long term follow up and are not reported in the All-Cause Mortality module.
|
|
General disorders
Abdominal pain
|
3.3%
1/30 • During study treatment (up to 3 years)
Only one mortality during study treatment window. All other mortalities occured during the long term follow up and are not reported in the All-Cause Mortality module.
|
|
Blood and lymphatic system disorders
Bruising
|
3.3%
1/30 • During study treatment (up to 3 years)
Only one mortality during study treatment window. All other mortalities occured during the long term follow up and are not reported in the All-Cause Mortality module.
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
3.3%
1/30 • During study treatment (up to 3 years)
Only one mortality during study treatment window. All other mortalities occured during the long term follow up and are not reported in the All-Cause Mortality module.
|
|
Gastrointestinal disorders
Flatulence
|
3.3%
1/30 • During study treatment (up to 3 years)
Only one mortality during study treatment window. All other mortalities occured during the long term follow up and are not reported in the All-Cause Mortality module.
|
|
General disorders
Hypomagnesemia
|
3.3%
1/30 • During study treatment (up to 3 years)
Only one mortality during study treatment window. All other mortalities occured during the long term follow up and are not reported in the All-Cause Mortality module.
|
|
Renal and urinary disorders
Creatinine increased
|
3.3%
1/30 • During study treatment (up to 3 years)
Only one mortality during study treatment window. All other mortalities occured during the long term follow up and are not reported in the All-Cause Mortality module.
|
Additional Information
Michelle Melisko, MD
University of California San Francisco
Phone: 415-353-7070
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place