Central Nervous System MetastasesNCT01939483
A Pilot Study of Irinotecan in Patients With Breast Cancer and CNS Metastases
A study testing irinotecan hydrochloride and laboratory biomarker analysis in people with Central Nervous System Metastases and Male Breast Cancer, run by University of California, Irvine.
Trial summary
This pilot clinical trial studies irinotecan hydrochloride in treating patients with breast cancer and brain metastases that progressed after whole brain radiation therapy or stereotactic radiosurgery. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Central Nervous System Metastases, Male Breast Cancer, Recurrent Breast Cancer
- What is being tested?
- irinotecan hydrochloride and laboratory biomarker analysis
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Dec 2012to Aug 2018
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed diagnosis of breast cancer (irrespective of receptor status), with evidence of CNS disease by computed tomography (CT) or magnetic resonance imaging (MRI), who have progressed after whole brain radiation therapy or stereotactic radiosurgery
- Patients must not be a candidate for surgical resection and/or further stereotactic radiosurgery
- Patients may have had an unlimited number of prior treatments, including any systemic chemotherapy (excluding prior progression of disease with topoisomerase inhibitors as explained below), surgical resection, whole brain radiation, stereotactic radiosurgery, or radioimmunotherapy
- Patient must have MRI of brain obtained within two weeks of study initiation for staging and patients must also receive first dose within two weeks of study enrollment
- Patients must have at least one measurable brain lesion prior to start of treatment (≥ 10 mm on T1-weighted, gadolinium-enhanced MRI)
- Karnofsky performance score greater than 60
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- At least two weeks must have elapsed since prior chemotherapy, three weeks must have elapsed since last surgery, and six weeks since completion of radiation therapy
- Hemoglobin > 9
- Absolute neutrophil count (ANC) > 1500
- Platelet count (plt) > 125
- Creatinine < 1.5
- Total bilirubin < 1.5
- Aspartate aminotransferase and alanine aminotransferase levels within five times the upper limit of normal
- Patients may be on oral corticosteroids at stable dose (no dose change within two weeks of enrollment), and may be on antiepileptic medication (except for cytochrome P450 3A4 (CYP3A4) enzyme-inducing antiepileptic medications)
- Fertile patients must use effective contraception
Who cannot join
- Pregnancy, lactation, immunosuppression other than corticosteroids
- Patient may be on hormonal therapy or Herceptin, but no other concurrent chemotherapy is allowed
- Patients who had progression of their breast cancer after prior administration of irinotecan are excluded
- Patients with leptomeningeal carcinomatosis as the only site of CNS involvement are excluded
- 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
- Patients using valproic acid within the last two weeks and patients with contraindications to anticholinergic agents will be excluded
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- Concurrent administration of CYP3A4 enzyme-inducing antiepileptic medications (e.g. phenytoin) will not be allowed (if patients are taking one of these agents, they must switch to a non- enzyme-inducing antiepileptic medication prior to start of treatment)
- No history of immediate or delayed-type hypersensitivity reaction to gadolinium contrast agents or other contraindication to gadolinium contrast, and no other known contraindication to MRI
- Homozygous for uridine diphosphate (UDP) glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1)*28 allele * All patients will be tested for UGT1A genotype prior to starting treatment and be excluded if they are homozygous for the UGT1A1*28 allele (UGT1A1 7/7 genotype); irinotecan's active metabolite glucuronidation of 7-ethyl-10-hydroxycamptothecin (SN-38) is inactivated through glucuronidation by uridine diphosphate glucuronosyltransferases (UGTs) mainly in the liver and is excreted through the bile ducts; a meta-analysis demonstrated that the UGT1A1*28 genotype is moderately predictive of severe irinotecan induced hematologic toxicity at moderate doses and strongly predictive at high doses, and in 2005, the Food and Drug Administration (FDA) added a warning to the irinotecan packaging label that patients with the UGT1A1*28 genotype were at increased risk for neutropenia
About this study
This pilot clinical trial studies irinotecan hydrochloride in treating patients with breast cancer and brain metastases that progressed after whole brain radiation therapy or stereotactic radiosurgery. Drugs used in chemotherapy, such as irinotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.
Read the detailed description
PRIMARY OBJECTIVES; I. To evaluate the safety and efficacy of irinotecan (irinotecan hydrochloride) in breast cancer patients with brain metastases who progressed after radiation therapy.
II. To estimate central nervous system (CNS) objective response and clinical benefit rate in patients with breast cancer and brain metastases treated with irinotecan.
III. To estimate progression free survival. IV. To estimate overall survival. V. To assess the toxicity of Irinotecan.
OUTLINE:
Patients receive irinotecan hydrochloride intravenously (IV) over 90 minutes on days 1, 8, 15, 22, and 29. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for up to 24 months.
- Conditions
- Central Nervous System Metastases, Male Breast Cancer, Recurrent Breast Cancer, Stage IV Breast Cancer
- Being tested
- irinotecan hydrochloride, laboratory biomarker analysis
- Keywords
- Irinotecan hydrochloride, Irinotecan, CAMPTOSAR
- Medical subject headings
- Breast Neoplasms, Male, Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Also called Campto, Camptosar, camptothecin-11, CPT-11
Given IV
laboratory biomarker analysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (irinotecan hydrochloride) | Experimental | Patients receive irinotecan hydrochloride IV over 90 minutes on days 1, 8, 15, 22, and 29. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity.
This arm also includes laboratory biomarker analysis as an intervention. Receives: Drug: irinotecan hydrochloride; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
CNS objective response (complete response or partial response), defined as at least 20% volumetric reduction of CNS lesions in absence of increasing steroid use, progressive neurologic signs and symptoms, or progressive extra-CNS disease, based on MRI
Measured: Up to 24 months
Response rate of patients who have remained progression-free, based on MRI
Measured: Up to 6 months
Secondary outcomes (4)
Overall survival
The product limit estimator developed by Kaplan and Meier was used to graphically describe the distribution of survival among patients with recurrent disease.
Measured: Time between treatment initiation and death, assessed up to 24 months
Progression free survival (PFS)
The product limit estimator developed by Kaplan and Meier was used to graphically describe the distribution of PFS among patients with recurrent disease.
Measured: Time between treatment initiation and disease progression/relapse/death, assessed up to 24 months
Clinical benefit rate (objective response + stable disease at least 16 weeks)
Measured: Up to 24 months
Frequency of toxicity occurrence, assessed by National Cancer Institute's Common Terminology Criteria (CTC) for Adverse Events version 4.0
Tabulated by type, and worst grade experienced by the patient. Toxicity will initially be summarized within each cohort or patient subgroup, and then collectively summarized.
Measured: Up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Sep 2013 (estimated)
- Study startDec 2012
- Primary completionAug 2017 (estimated)
- Study completionAug 2018 (estimated)
Why it stopped: Slow accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Central Nervous System MetastasesStudies of the same condition, open and under way.
- More trials run by University of California, IrvineThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, Irvine
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Rita Sanghvi, Mehta, University of California, Irvine
- Investigators
- Rita Mehta, MD, Principal investigator, University of California, Irvine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01939483
- Sponsor's protocol ID
- UCI 11-22
- Other IDs
- 2011-8497, NCI-2013-01136
- Status last verified
- Oct 2014
- First submitted
- 6 Sep 2013
- Last updated
- 8 Oct 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of Irinotecan in Patients With Breast Cancer and CNS Metastases
- ClinicalTrials.gov ID
- NCT01939483
- Acronym / sponsor ID
- UCI 11-22
- Conditions
- Central Nervous System Metastases, Male Breast Cancer, Recurrent Breast Cancer, Stage IV Breast Cancer
- Keywords
- Irinotecan hydrochloride, Irinotecan, CAMPTOSAR
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Slow accrual
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of California, IrvineUniversity, hospital or other
- Study start
- Dec 2012
- Primary completion
- Aug 2017 (estimated)
- Study completion
- Aug 2018 (estimated)
- First posted
- 11 Sep 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This pilot clinical trial studies irinotecan hydrochloride in treating patients with breast cancer and brain metastases that progressed after whole brain radiation therapy or stereotactic radiosurgery. Drugs used in chemotherapy, such as irinotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.
Detailed description
PRIMARY OBJECTIVES; I. To evaluate the safety and efficacy of irinotecan (irinotecan hydrochloride) in breast cancer patients with brain metastases who progressed after radiation therapy.
II. To estimate central nervous system (CNS) objective response and clinical benefit rate in patients with breast cancer and brain metastases treated with irinotecan.
III. To estimate progression free survival. IV. To estimate overall survival. V. To assess the toxicity of Irinotecan.
OUTLINE:
Patients receive irinotecan hydrochloride intravenously (IV) over 90 minutes on days 1, 8, 15, 22, and 29. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for up to 24 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (irinotecan hydrochloride) | Experimental | Drug: irinotecan hydrochloride, Other: laboratory biomarker analysisPatients receive irinotecan hydrochloride IV over 90 minutes on days 1, 8, 15, 22, and 29. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity. This arm also includes laboratory biomarker analysis as an intervention. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Histologically confirmed diagnosis of breast cancer (irrespective of receptor status), with evidence of CNS disease by computed tomography (CT) or magnetic resonance imaging (MRI), who have progressed after whole brain radiation therapy or stereotactic radiosurgery
- Patients must not be a candidate for surgical resection and/or further stereotactic radiosurgery
- Patients may have had an unlimited number of prior treatments, including any systemic chemotherapy (excluding prior progression of disease with topoisomerase inhibitors as explained below), surgical resection, whole brain radiation, stereotactic radiosurgery, or radioimmunotherapy
- Patient must have MRI of brain obtained within two weeks of study initiation for staging and patients must also receive first dose within two weeks of study enrollment
- Patients must have at least one measurable brain lesion prior to start of treatment (≥ 10 mm on T1-weighted, gadolinium-enhanced MRI)
Key exclusion criteria (9 listed)
- Pregnancy, lactation, immunosuppression other than corticosteroids
- Patient may be on hormonal therapy or Herceptin, but no other concurrent chemotherapy is allowed
- Patients who had progression of their breast cancer after prior administration of irinotecan are excluded
- Patients with leptomeningeal carcinomatosis as the only site of CNS involvement are excluded
- 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
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 hydrochlorideAlso: Campto, Camptosar, camptothecin-11, CPT-11Given IV | Drug | Treatment (irinotecan hydrochloride) |
| laboratory biomarker analysisCorrelative studies | Other | Treatment (irinotecan hydrochloride) |
Primary outcome
CNS objective response (complete response or partial response), defined as at least 20% volumetric reduction of CNS lesions in absence of increasing steroid use, progressive neurologic signs and symptoms, or progressive extra-CNS disease, based on MRI
Time frame: Up to 24 months
Response rate of patients who have remained progression-free, based on MRI
Time frame: Up to 6 months
4 secondary outcomes
Overall survival
Time frame: Time between treatment initiation and death, assessed up to 24 months
Progression free survival (PFS)
Time frame: Time between treatment initiation and disease progression/relapse/death, assessed up to 24 months
Clinical benefit rate (objective response + stable disease at least 16 weeks)
Time frame: Up to 24 months
Frequency of toxicity occurrence, assessed by National Cancer Institute's Common Terminology Criteria (CTC) for Adverse Events version 4.0
Time frame: Up to 24 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2014.
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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.
Rita Mehta, MD principal investigator
University of California, Irvine
Questions about this trial
What is this clinical trial studying?
A study testing irinotecan hydrochloride and laboratory biomarker analysis in people with Central Nervous System Metastases and Male Breast Cancer, run by University of California, Irvine.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 9 exclusion criteria. 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: withdrawn, as of the sponsor's last update on 8 Oct 2014. Status can change between updates, so confirm with the study contact before making plans.
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.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
CNS objective response (complete response or partial response), defined as at least 20% volumetric reduction of CNS lesions in absence of increasing steroid use, progressive neurologic signs and symptoms, or progressive extra-CNS disease, based on MRI (time frame: Up to 24 months). 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 8 Oct 2014.