Central Nervous System MetastasesPhase 2NCT00992602
Liposomal Cytarabine and High-Dose Methotrexate in Treating Patients With Central Nervous System Metastases From Breast Cancer
A Phase 2 study testing methotrexate, liposomal cytarabine and quality-of-life assessment in people with Central Nervous System Metastases and Leptomeningeal Metastases, run by University of Washington at 1 site in United States.
Trial summary
This phase II trial studies how well giving liposomal cytarabine and high-dose methotrexate works in treating patients with breast cancer that has spread to the central nervous system. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Central Nervous System Metastases, Leptomeningeal Metastases, Recurrent Breast Cancer
- What is being tested?
- methotrexate, liposomal cytarabine and quality-of-life assessment
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2011to Oct 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 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Women who are not pregnant (contraception must be used throughout the study)
- Diagnosis of breast cancer with metastases to CNS (regardless of receptor status); leptomeningeal disease must be present with/without parenchymal brain involvement
- Able to provide informed consent
- No prior treatment with whole brain radiotherapy (WBRT); if patient received stereotactic radiosurgery (SRS) prior to enrollment it must be well documented which lesions were treated and untreated index lesions for follow up must be identified; no treatment with SRS will be permitted while on the study; CNS disease must be documented by MRI and CSF cytology
- Karnofsky Performance Status > 60
- White blood cells (WBC) >= 3.0 K
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- Absolute neutrophil count (ANC) >= 1.5 K
- Platelets (PLT) >= 100 K
- Hematocrit (HCT) >= 30%
- Glomerular filtration rate (GFR) >= 60 mL/min
- Acceptable liver function (see exclusion criteria)
- Any ongoing therapy for systemic disease allows for the addition of systemic HD-MTX and IT Depocyt; in general patients receiving trastuzumab or lapatinib at the time of enrollment will be allowed to continue; bisphosphonates (i.e., zoledronic acid) and denosumab will be allowed; other non-CNS active chemotherapies might be allowed if no known interactions with study drugs are present; this must be reviewed and approved by the primary investigator on a case-by-case basis
- Mini-mental state examination score of 24 or above
Who cannot join
- Serum bilirubin > 1.5 x the upper limit of reference range (ULRR)
- Serum creatinine > 1.5 x ULRR or creatinine clearance =< 60 mL/minute (calculated by Cockcroft-Gault formula)
- Potassium, < 3.7 mmol/L despite supplementation; serum calcium (ionized or adjusted for albumin,) or magnesium out of normal range despite supplementation
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.5 x ULRR
- Alkaline phosphatase (ALP) > 2.5 x ULRR or > 5 x ULRR if judged by the investigator to be related to liver metastases
- Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol
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- Patients with known pleural effusion or ascites
- Prior treatment with whole brain radiotherapy (prior treatment with SRS is allowed under conditions provided in the inclusion criteria)
- Previous allergic or adverse reaction to methotrexate or cytarabine
- Prior treatment with systemic HD-MTX, IT liposomal cytarabine, or IT therapy of any kind
- Prior IT therapy of any kind
- Women who are currently pregnant or breast feeding
- Previous or current malignancies of other histologies within the last 5 years, with the exception of cervical carcinoma in situ and adequately treated basal cell or squamous cell carcinoma of the skin
- Receipt of any investigational agents within 30 days prior to commencing study treatment
- Last dose of prior chemotherapy was less than 4 weeks before the start of study therapy; patients who had no toxicities with prior chemotherapy can start study treatment earlier than 4 weeks
- Stereotactic radiosurgery (SRS) less than 2 weeks before the start of study therapy
- Any unresolved toxicity greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 from previous anti-cancer therapy
- Previous enrollment in the present study
- Major surgery within 4 weeks prior to starting therapy, with the exception of the Ommaya reservoir which can be used for introduction of chemotherapy within 48-72 hours after placement
Trial locations and contacts
1 site in 1 country.
United States1 site
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, 98109
About this study
Official title: Phase II Study of the Combination of High-Dose Methotrexate and Intrathecal Liposomal Cytarabine in Patients With Leptomeningeal Metastases With or Without Parenchymal Brain Involvement
This phase II trial studies how well giving liposomal cytarabine and high-dose methotrexate works in treating patients with breast cancer that has spread to the central nervous system. Drugs used in chemotherapy, such as liposomal cytarabine and methotrexate, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving liposomal cytarabine with high-dose methotrexate may kill more tumor cells.
Read the detailed description
PRIMARY OBJECTIVES:
- To show that treatment with high-dose methotrexate (HD-MTX) in combination with intrathecal (IT) sustained-release cytarabine (liposomal cytarabine) will result in median progression-free survival (PFS) greater than 7 weeks for patients with breast cancer and leptomeningeal metastases with or without parenchymal brain involvement.
SECONDARY OBJECTIVES:
- To describe the overall survival of patients with central nervous system (CNS) metastatic breast cancer treated with the combination of intravenous (IV) HD-MTX and IT Depocyt (liposomal cytarabine).
II. To describe the safety of the combination therapy, in terms of toxicity, adverse events, and the need for dose reductions or schedule modification.
III. To estimate the best overall response rate achieved during treatment with IV HD-MTX and IT Depocyt. Radiographic response will be measured by the Macdonald Criteria using imaging (magnetic resonance imaging [MRI]), and cytologic response will be measured by cerebrospinal fluid (CSF) cytology.
IV. To determine the number of treatment cycles needed to achieve radiographic and cytologic response.
- To describe response duration in patients who achieve at least partial radiographic response and cytologic clearance.
VI. To define time to clinical progression as measured by Karnofsky performance status (KPS) and neurological exam.
VII. To describe functional status and quality of life of patients, through clinical evaluations of neurological status and patient-reported quality of life (QOL) measured by the Functional Assessment of Chronic Illness Therapy (FACIT) brain and/or CNS questionnaires.
VIII. To correlate response rates with the extent of patient's systemic disease and tumor receptor status (estrogen receptor [ER], progesterone receptor [PR], human epidermal growth factor receptor 2 [Her2]/neu and/or breast cancer, early onset [BRCA] if applicable).
OUTLINE:
INDUCTION THERAPY (WEEKS 1-6): Patients liposomal cytarabine IT or via lumbar puncture (LP) every 14 days beginning in week 1. Patients also receive high-dose methotrexate IV every 14 days beginning in week 2. Treatment repeats every 14 days for 3 courses in the absence of disease progression or unacceptable toxicity.
CONSOLIDATION THERAPY (WEEKS 7-11): Patients achieving complete response (CR), partial response (PR), or stable disease (SD) and CSF negative for malignant cells receive liposomal cytarabine IT or via LP beginning in week 7 and high-dose methotrexate IV beginning in week 8. Treatment repeats every 2 weeks for 2 courses in the absence of disease progression or unacceptable toxicity.
MAINTENANCE THERAPY (WEEKS 13-37): Patients achieving CR, PR, or SD and CSF negative for malignant cells receive liposomal cytarabine IT or via LP every 4 weeks beginning in week 13 and high-dose methotrexate IV monthly beginning in week 15. Treatment with liposomal cytarabine repeats every 4 weeks for up to 5 courses and treatment with high-dose methotrexate repeats monthly for up to 6 courses in the absence of disease progression or unacceptable toxicity.
- Conditions
- Central Nervous System Metastases, Leptomeningeal Metastases, Recurrent Breast Cancer, Stage IV Breast Cancer, Tumors Metastatic to Brain
- Being tested
- methotrexate, liposomal cytarabine, quality-of-life assessment, laboratory biomarker analysis
- Medical subject headings
- Meningeal Carcinomatosis, Breast Neoplasms, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
methotrexateDrug
Also called amethopterin, Folex, methylaminopterin, Mexate
Given IV
liposomal cytarabineDrug
Also called cytarabine liposome, DepoCyt, DepoCyte, DepoFoam-encapsulated cytarabine
Given IT or via LP
quality-of-life assessmentOther
Also called quality of life assessment
Ancillary studies
laboratory biomarker analysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (liposomal cytarabine, high-dose methotrexate) | Experimental | See Detailed Description Receives: Drug: methotrexate; Drug: liposomal cytarabine; Other: quality-of-life assessment; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Survival Free of Neurological Progression, Measured in Weeks
Neurological progression defined by either clinical impression (measured by Karnofsky Performance Status), radiographical response (using Macdonald criteria), or cytologic response (measured by CSF cytology).
Measured: Time from start of therapy, assessed up to 4 years
Secondary outcomes (1)
Overall Survival
Measured: Time from start of therapy until death, assessed up to 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Oct 2009 (estimated)
- Study startApr 2011
- Primary completionJun 2013
- Study completionOct 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 Central Nervous System MetastasesStudies of the same condition, open and under way.
- More trials run by University of WashingtonThe 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
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Washington
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Maciej Mrugala, University of Washington
- Investigators
- Maciej Mrugala, Principal investigator, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00992602
- Sponsor's protocol ID
- 6954
- Other IDs
- NCI-2009-01309, 6954, P30CA015704
- Status last verified
- Jun 2017
- First submitted
- 7 Oct 2009
- Last updated
- 7 Jul 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 7 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of the Combination of High-Dose Methotrexate and Intrathecal Liposomal Cytarabine in Patients With Leptomeningeal Metastases With or Without Parenchymal Brain Involvement
- ClinicalTrials.gov ID
- NCT00992602
- Acronym / sponsor ID
- 6954
- Conditions
- Central Nervous System Metastases, Leptomeningeal Metastases, Recurrent Breast Cancer, Stage IV Breast Cancer, Tumors Metastatic to Brain
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 3 participants (actual)
- Lead sponsor
- University of WashingtonUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Apr 2011
- Primary completion
- Jun 2013 (actual)
- Study completion
- Oct 2014 (actual)
- First posted
- 9 Oct 2009 (estimated)
- Results
- Posted 7 Jul 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II trial studies how well giving liposomal cytarabine and high-dose methotrexate works in treating patients with breast cancer that has spread to the central nervous system. Drugs used in chemotherapy, such as liposomal cytarabine and methotrexate, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving liposomal cytarabine with high-dose methotrexate may kill more tumor cells.
Detailed description
PRIMARY OBJECTIVES:
- To show that treatment with high-dose methotrexate (HD-MTX) in combination with intrathecal (IT) sustained-release cytarabine (liposomal cytarabine) will result in median progression-free survival (PFS) greater than 7 weeks for patients with breast cancer and leptomeningeal metastases with or without parenchymal brain involvement.
SECONDARY OBJECTIVES:
- To describe the overall survival of patients with central nervous system (CNS) metastatic breast cancer treated with the combination of intravenous (IV) HD-MTX and IT Depocyt (liposomal cytarabine).
II. To describe the safety of the combination therapy, in terms of toxicity, adverse events, and the need for dose reductions or schedule modification.
III. To estimate the best overall response rate achieved during treatment with IV HD-MTX and IT Depocyt. Radiographic response will be measured by the Macdonald Criteria using imaging (magnetic resonance imaging [MRI]), and cytologic response will be measured by cerebrospinal fluid (CSF) cytology.
IV. To determine the number of treatment cycles needed to achieve radiographic and cytologic response.
- To describe response duration in patients who achieve at least partial radiographic response and cytologic clearance.
VI. To define time to clinical progression as measured by Karnofsky performance status (KPS) and neurological exam.
VII. To describe functional status and quality of life of patients, through clinical evaluations of neurological status and patient-reported quality of life (QOL) measured by the Functional Assessment of Chronic Illness Therapy (FACIT) brain and/or CNS questionnaires.
VIII. To correlate response rates with the extent of patient's systemic disease and tumor receptor status (estrogen receptor [ER], progesterone receptor [PR], human epidermal growth factor receptor 2 [Her2]/neu and/or breast cancer, early onset [BRCA] if applicable).
OUTLINE:
INDUCTION THERAPY (WEEKS 1-6): Patients liposomal cytarabine IT or via lumbar puncture (LP) every 14 days beginning in week 1. Patients also receive high-dose methotrexate IV every 14 days beginning in week 2. Treatment repeats every 14 days for 3 courses in the absence of disease progression or unacceptable toxicity.
CONSOLIDATION THERAPY (WEEKS 7-11): Patients achieving complete response (CR), partial response (PR), or stable disease (SD) and CSF negative for malignant cells receive liposomal cytarabine IT or via LP beginning in week 7 and high-dose methotrexate IV beginning in week 8. Treatment repeats every 2 weeks for 2 courses in the absence of disease progression or unacceptable toxicity.
MAINTENANCE THERAPY (WEEKS 13-37): Patients achieving CR, PR, or SD and CSF negative for malignant cells receive liposomal cytarabine IT or via LP every 4 weeks beginning in week 13 and high-dose methotrexate IV monthly beginning in week 15. Treatment with liposomal cytarabine repeats every 4 weeks for up to 5 courses and treatment with high-dose methotrexate repeats monthly for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (liposomal cytarabine, high-dose methotrexate) | Experimental | Drug: methotrexate, Drug: liposomal cytarabine, Other: quality-of-life assessment, Other: laboratory biomarker analysisSee Detailed Description |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Women who are not pregnant (contraception must be used throughout the study)
- Diagnosis of breast cancer with metastases to CNS (regardless of receptor status); leptomeningeal disease must be present with/without parenchymal brain involvement
- Able to provide informed consent
- No prior treatment with whole brain radiotherapy (WBRT); if patient received stereotactic radiosurgery (SRS) prior to enrollment it must be well documented which lesions were treated and untreated index lesions for follow up must be identified; no treatment with SRS will be permitted while on the study; CNS disease must be documented by MRI and CSF cytology
- Karnofsky Performance Status > 60
Key exclusion criteria (19 listed)
- Serum bilirubin > 1.5 x the upper limit of reference range (ULRR)
- Serum creatinine > 1.5 x ULRR or creatinine clearance =< 60 mL/minute (calculated by Cockcroft-Gault formula)
- Potassium, < 3.7 mmol/L despite supplementation; serum calcium (ionized or adjusted for albumin,) or magnesium out of normal range despite supplementation
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.5 x ULRR
- Alkaline phosphatase (ALP) > 2.5 x ULRR or > 5 x ULRR if judged by the investigator to be related to liver metastases
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 |
|---|---|---|
| methotrexateAlso: amethopterin, Folex, methylaminopterin, MexateGiven IV | Drug | Treatment (liposomal cytarabine, high-dose methotrexate) |
| liposomal cytarabineAlso: cytarabine liposome, DepoCyt, DepoCyte, DepoFoam-encapsulated cytarabineGiven IT or via LP | Drug | Treatment (liposomal cytarabine, high-dose methotrexate) |
| quality-of-life assessmentAlso: quality of life assessmentAncillary studies | Other | Treatment (liposomal cytarabine, high-dose methotrexate) |
| laboratory biomarker analysisCorrelative studies | Other | Treatment (liposomal cytarabine, high-dose methotrexate) |
Primary outcome
Survival Free of Neurological Progression, Measured in Weeks
Time frame: Time from start of therapy, assessed up to 4 years
Neurological progression defined by either clinical impression (measured by Karnofsky Performance Status), radiographical response (using Macdonald criteria), or cytologic response (measured by CSF cytology).
1 secondary outcome
Overall Survival
Time frame: Time from start of therapy until death, assessed up to 4 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jul 2017.
- 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.
Maciej Mrugala principal investigator
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
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 methotrexate, liposomal cytarabine and quality-of-life assessment in people with Central Nervous System Metastases and Leptomeningeal Metastases, run by University of Washington 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?
The sponsor lists 13 inclusion and 19 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: finished, as of the sponsor's last update on 7 Jul 2017. 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 7 Jul 2017). 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?
Survival Free of Neurological Progression, Measured in Weeks (time frame: Time from start of therapy, assessed up to 4 years). 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 7 Jul 2017.