Breast CancerPhase 2NCT00617539
Irinotecan and Temozolomide in Treating Patients With Breast Cancer Who Have Received Previous Treatment for Brain Metastases
A Phase 2 study testing irinotecan hydrochloride and temozolomide in people with Breast Cancer and Metastatic Cancer, run by University of California, San Francisco at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Breast Cancer, Metastatic Cancer
- What is being tested?
- irinotecan hydrochloride and temozolomide
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2005to Jan 2014
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
DISEASE CHARACTERISTICS:
- Histologically or cytologically confirmed breast cancer with radiographically confirmed metastases to the brain
- Extracranial metastases allowed
- Must have demonstrated progression of brain metastases after prior treatment for brain metastases, including any of the following:
- External beam radiotherapy
- Brachytherapy
- Stereotactic radiosurgery
- Surgery
- Chemotherapy
- Treatments with investigational drugs, biologics, or devices
- Disease progression in the CNS must meet ≥ 1 of the following criteria:
- New lesions in the CNS on an imaging study (contrast-enhanced CT scan or MRI)
- Progressive lesions on an imaging study (contrast-enhanced CT scan or MRI)
- 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:
- Curatively treated basal or squamous cell carcinoma of the skin
- Carcinoma in situ of the cervix
- Other malignancies considered disease-free
- 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:
- Cardiac pacemaker
- Implanted cardiac defibrillator
- Brain aneurysm clips
- Cochlear implant
- Ocular foreign body
- Shrapnel
- No active or uncontrolled infection
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- Recovered from the side effects of prior chemotherapy, surgery, or radiotherapy for extracranial disease or brain metastases
- Concurrent trastuzumab, bisphosphonate, and/or corticosteroid therapy allowed
- At least 1 week since prior or on current stable dose of corticosteroid therapy
- Patients on an enzyme-inducing anti-epileptic agent (EIAE) or valproic acid are eligible if they are switched to an alternate non-EIAE medication
- Concurrent coumadin allowed
- No prophylactic use of filgrastim (G-CSF) during first course of treatment
Trial locations and contacts
1 site in 1 country.
United States1 site
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, 94115
About this study
Official title: A Phase II Study of Irinotecan and Temozolomide in Breast Cancer Patients With Brian Metastases That Have Progressed After Stereotactic Radiosurgery or Whole Brain Radiation
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.
Read the detailed description
OBJECTIVES:
Primary
- To evaluate the objective response rate systemically and in the CNS to the combination of irinotecan hydrochloride and temozolomide among patients with breast cancer and progressive brain metastases that have progressed after previous treatment for brain metastases.
- To determine the toxicities associated with the combination of irinotecan hydrochloride and temozolomide in breast cancer patients with progressive brain metastases.
Secondary
- To evaluate the time to first progression at any site (CNS or extra-CNS) in patients treated with the combination of irinotecan hydrochloride and temozolomide.
- To evaluate the overall survival of patients treated with the combination of irinotecan hydrochloride and temozolomide for brain metastases.
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.
- Conditions
- Breast Cancer, Metastatic Cancer
- Being tested
- irinotecan hydrochloride, temozolomide
- Keywords
- recurrent breast cancer, stage IV breast cancer, male breast cancer, tumors metastatic to brain
- Medical subject headings
- Breast Neoplasms, Neoplasm Metastasis, Breast Neoplasms, Male, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| irinotecan and temozolomide | Experimental | Not described Receives: Drug: irinotecan hydrochloride; Drug: temozolomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: From 1 day 1 (first day of treatment) every 8 weeks until scan shows disease progression or up to 2 years
Secondary outcomes (3)
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.
Measured: 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
Measured: 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
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Feb 2008 (estimated)
- Study startFeb 2005
- Primary completionJan 2013
- Study completionJan 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Michelle Melisko, MD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00617539
- Sponsor's protocol ID
- 05751
- Other IDs
- UCSF-05751
- Status last verified
- Mar 2018
- First submitted
- 15 Feb 2008
- Last updated
- 20 Apr 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 20 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Irinotecan and Temozolomide in Breast Cancer Patients With Brian Metastases That Have Progressed After Stereotactic Radiosurgery or Whole Brain Radiation
- ClinicalTrials.gov ID
- NCT00617539
- Acronym / sponsor ID
- 05751
- Conditions
- Breast Cancer, Metastatic Cancer
- Keywords
- recurrent breast cancer, stage IV breast cancer, male breast cancer, tumors metastatic to brain
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Feb 2005
- Primary completion
- Jan 2013 (actual)
- Study completion
- Jan 2014 (actual)
- First posted
- 18 Feb 2008 (estimated)
- Results
- Posted 20 Apr 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
OBJECTIVES:
Primary
- To evaluate the objective response rate systemically and in the CNS to the combination of irinotecan hydrochloride and temozolomide among patients with breast cancer and progressive brain metastases that have progressed after previous treatment for brain metastases.
- To determine the toxicities associated with the combination of irinotecan hydrochloride and temozolomide in breast cancer patients with progressive brain metastases.
Secondary
- To evaluate the time to first progression at any site (CNS or extra-CNS) in patients treated with the combination of irinotecan hydrochloride and temozolomide.
- To evaluate the overall survival of patients treated with the combination of irinotecan hydrochloride and temozolomide for brain metastases.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| irinotecan and temozolomide | Experimental | Drug: irinotecan hydrochloride, Drug: temozolomide |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| irinotecan hydrochloride | Drug | irinotecan and temozolomide |
| temozolomide | Drug | irinotecan and temozolomide |
Primary outcome
Number of Patients With Objective Treatment Response (Complete or Partial) in the CNS
Time frame: 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
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.
Number of Patients Experiencing a Clinical Benefit
Time frame: From 1 day 1 (first day of treatment) every 8 weeks until scan shows disease progression or up to 2 years
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.
3 secondary outcomes
Time to First Progression in CNS
Time frame: 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 frame: 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
Time frame: 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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Apr 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michelle Melisko, MD principal investigator
University of California, San Francisco
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing irinotecan hydrochloride and temozolomide in people with Breast Cancer and Metastatic Cancer, run by University of California, San Francisco at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Apr 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Patients With Objective Treatment Response (Complete or Partial) in the CNS (time frame: 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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Apr 2018.