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| ID | Type | Description | Link |
|---|---|---|---|
| UCSF-05751 |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
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RATIONALE: Drugs used in chemotherapy, such as irinotecan and temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells.
PURPOSE: This phase II trial is studying the side effects of giving irinotecan together with temozolomide and to see how well it works in treating patients with breast cancer who have received previous treatment for brain metastases.
OBJECTIVES:
Primary
Secondary
OUTLINE: Patients receive irinotecan IV on days 1 and 15 and oral temozolomide on days 1-7 and 15-21. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study therapy, patients are followed every 4 weeks.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| irinotecan and temozolomide | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| irinotecan hydrochloride | Drug |
| ||
| temozolomide |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Patients With Objective Treatment Response (Complete or Partial) in the CNS | 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. | 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 |
| Number of Patients Experiencing a Clinical Benefit | The 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. | From 1 day 1 (first day of treatment) every 8 weeks until scan shows disease progression or up to 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| Time to First Progression in CNS | Imaging 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. |
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DISEASE CHARACTERISTICS:
Histologically or cytologically confirmed breast cancer with radiographically confirmed metastases to the brain
Must have demonstrated progression of brain metastases after prior treatment for brain metastases, including any of the following:
Disease progression in the CNS must meet ≥ 1 of the following criteria:
New or progressive lesions that do not meet measurable disease definition allowed
Leptomeningeal disease allowed if concurrent progression or parenchymal brain metastases
Not a candidate for surgical resection and/or further stereotactic radiosurgery
Hormone receptor status not specified
PATIENT CHARACTERISTICS:
Menopausal status not specified
ECOG performance status 0-2
Life expectancy ≥ 1 month
Hemoglobin ≥ 10 g/dL (transfusion allowed)
ANC ≥ 1,500/mm³
Granulocyte count ≥ 1,500/mm³
Platelet count ≥ 100,000/mm³
Creatinine ≤ 1.5 mg/dL
Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
AST and ALT ≤ 3 times ULN
Must be able to swallow and retain oral medications
No other active malignancy except for any of the following:
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No history of immediate or delayed-type hypersensitivity reaction to gadolinium contrast agents or other contraindication to gadolinium contrast
No other known contraindication to MRI including, but not limited to, any of the following:
No active or uncontrolled infection
PRIOR CONCURRENT THERAPY:
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| Name | Affiliation | Role |
|---|---|---|
| Michelle Melisko, MD | University of California, San Francisco | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UCSF Helen Diller Family Comprehensive Cancer Center | San Francisco | California | 94115 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| 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 |
| Overall Time of Survival | Time from initiation of study participation until death | Time from initiation of study participation until death or up to 3 years |
| Number of Patients Whose Circulating Tumor Cells (CTCs) Decreased From >5 to <5 CTCs Per 7.5 mL | CTCs were measured in blood using the Cellsearch(R) assay in 14 of the 20 patients measured at baseline | 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 years |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | 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 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Full Range | years |
| |||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants | No |
| |||||||||||||||||
| Region of Enrollment | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Patients With Objective Treatment Response (Complete or Partial) in the CNS | 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. | Posted | Count of Participants | Participants | 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 |
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| |||||||||||||||||||||||||||
| Secondary | Time to First Progression in CNS | Imaging 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. | Posted | Median | Full Range | Days | 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 |
|
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| Secondary | Overall Time of Survival | Time from initiation of study participation until death | Posted | Median | Full Range | Days | Time from initiation of study participation until death or up to 3 years |
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| |||||||||||||||||||||||||||
| Secondary | Number of Patients Whose Circulating Tumor Cells (CTCs) Decreased From >5 to <5 CTCs Per 7.5 mL | CTCs were measured in blood using the Cellsearch(R) assay in 14 of the 20 patients measured at baseline | Of 20 patients with CTCs measured at baseline, 14 were also measured at 8 weeks | Posted | Number | participants | 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 years |
|
| |||||||||||||||||||||||||||
| Primary | Number of Patients Experiencing a Clinical Benefit | The 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. | Posted | Count of Participants | Participants | From 1 day 1 (first day of treatment) every 8 weeks until scan shows disease progression or up to 2 years |
|
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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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Irinotecan and Temozolomide | 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. | 14 | 30 | 16 | 30 | 30 | 30 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Infection | Infections and infestations | CTCAE (3.0) | Non-systematic Assessment |
| |
| Hyponatremia | Renal and urinary disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Fatigue | General disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Diarrhea | Gastrointestinal disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Transaminitis | Hepatobiliary disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Neuropathy | Nervous system disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Lymphopenia | Blood and lymphatic system disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Anemia | Blood and lymphatic system disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Dehydration | General disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Alkaline phosphatase increased | General disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Mental status change | Nervous system disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Weakness | General disorders | CTCAE (3.0) | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Infection | Infections and infestations | CTCAE (3.0) | Non-systematic Assessment |
| |
| Hyponatremia | Renal and urinary disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Fatigue | General disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Diarrhea | Gastrointestinal disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Transaminitis | Hepatobiliary disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Neuropathy | Nervous system disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Hypocalcemia | Endocrine disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Mucositis | Gastrointestinal disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Hypokalemia | Renal and urinary disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Anorexia | General disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Dizziness | Nervous system disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Lymphopenia | Blood and lymphatic system disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Anemia | Blood and lymphatic system disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Dehydration | General disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Hypoalbuminemia | Metabolism and nutrition disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Fever | General disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Hyperbilirubinemia | Hepatobiliary disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Alkaline phosphatase increased | Metabolism and nutrition disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Weakness | General disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Xerostomia | Gastrointestinal disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Abdominal pain | General disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Bruising | Blood and lymphatic system disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Flatulence | Gastrointestinal disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Hypomagnesemia | General disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Creatinine increased | Renal and urinary disorders | CTCAE (3.0) | Non-systematic Assessment |
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Michelle Melisko, MD | University of California San Francisco | 415-353-7070 | Michelle.Melisko@ucsf.edu |
| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| D009362 | Neoplasm Metastasis |
| D018567 | Breast Neoplasms, Male |
| D001932 | Brain Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D009385 | Neoplastic Processes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D016543 | Central Nervous System Neoplasms |
| D009423 | Nervous System Neoplasms |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| D000077146 | Irinotecan |
| D000077204 | Temozolomide |
| ID | Term |
|---|---|
| D002166 | Camptothecin |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
| D003606 | Dacarbazine |
| D014226 | Triazenes |
| D009930 | Organic Chemicals |
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
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