Intrathecal Trastuzumab for Leptomeningeal Metastases in HER2+ Breast Cancer
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ClinicalTrials.gov Identifier: NCT01325207 |
Recruitment Status :
Completed
First Posted : March 29, 2011
Results First Posted : May 28, 2019
Last Update Posted : September 26, 2019
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Tracking Information | ||||
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First Submitted Date ICMJE | March 7, 2011 | |||
First Posted Date ICMJE | March 29, 2011 | |||
Results First Submitted Date ICMJE | April 5, 2019 | |||
Results First Posted Date ICMJE | May 28, 2019 | |||
Last Update Posted Date | September 26, 2019 | |||
Study Start Date ICMJE | August 1, 2011 | |||
Actual Primary Completion Date | June 20, 2016 (Final data collection date for primary outcome measure) | |||
Current Primary Outcome Measures ICMJE |
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Original Primary Outcome Measures ICMJE |
Determine the safety and maximum tolerated dose of IT trastuzumab. [ Time Frame: treated twice a week for 4 weeks, then once a week for 4 weeks, and then every 2 weeks ] The initial phase of this study will be a dose escalation trial of 3-6 patients per each dose level. Dose escalation will occur until the MTD or the maximal defined dose (MDD) (40 mg) is reached. The starting dose will be 10 mg for cohort 1, 20 mg for cohort 2, 30 mg for cohort 3 and 40 mg for cohort 4. Patients will be treated twice a week for 4 weeks, then once a week for 4 weeks, and then every 2 weeks. The starting dose is based on the safety of this dose and higher doses as reported in the literature. The MTD or MDD will be used for phase II.
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Change History | ||||
Current Secondary Outcome Measures ICMJE | Not Provided | |||
Original Secondary Outcome Measures ICMJE |
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Current Other Pre-specified Outcome Measures |
Define the CSF PK of IT Trastuzumab. [ Time Frame: CSF analysis for cytology will be done every 2 weeks when CSF is obtained for PK and then every 4 weeks ] Patients may need a CSF flow study at the discretion of the treating principal investigator. If a spinal block is seen by CSF flow study or MRI, it will need local RT prior to treatment. Concurrent radiation is not allowed.
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Original Other Pre-specified Outcome Measures | Not Provided | |||
Descriptive Information | ||||
Brief Title ICMJE | Intrathecal Trastuzumab for Leptomeningeal Metastases in HER2+ Breast Cancer | |||
Official Title ICMJE | Phase I/II Dose Escalation Trial to Assess Safety of Intrathecal Trastuzumab for the Treatment of Leptomeningeal Metastases in HER2 Positive Breast Cancer | |||
Brief Summary | The drug being studied is Trastuzumab, a medicine that is used to slow or stop the growth of cancerous tumors that are HER-2 positive. Patients are being asked to participate in this study because they have been diagnosed with having tumor cells in their spinal fluid. This study will investigate the safety and effects of this drug when given directly into the spinal fluid. Phase I/II Dose Escalation Trial to Assess Safety of Intrathecal Trastuzumab for the Treatment of Leptomeningeal Metastases in HER2 Positive Breast Cancer The purpose of this research study is to determine a safe dose of the drug Trastuzumab and then determine how effective this treatment is. |
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Detailed Description | Phase I: Patients will be treated in cohorts of 3-6 based on standard phase I dose escalation parameters requiring 0/3 or 1/6 patients per cohort to have a DLT before dose escalation. Dosing is as follows: Cohort 1-10 mg IT, cohort 2-20 mg IT, cohort 3-30 mg IT and cohort 4-40 mg IT. Patients will be treated twice a week for 4 weeks, then once a week for 4 weeks, and then every 2 weeks. Toxicity for DLT will be assessed during first 4 weeks of treatment. Phase II: Patients will be treated with the MTD or maximal defined dose. Patients will be treated twice a week for 4 weeks, then once a week for 4 weeks, and then every 2 weeks. | |||
Study Type ICMJE | Interventional | |||
Study Phase ICMJE | Phase 1 Phase 2 |
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Study Design ICMJE | Intervention Model: Sequential Assignment Masking: None (Open Label) Primary Purpose: Treatment |
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Condition ICMJE | Breast Cancer | |||
Intervention ICMJE | Radiation: Trastuzumab
Trastuzumab will be administered twice per week for 4 weeks, then once per week for 4 weeks, and then every 2 weeks
Other Names:
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Study Arms ICMJE | Experimental: intravenous trastuzumab infusions
A Phase I single dose study (H0407g) of intravenous trastuzumab infusions ranging from 10-500 mg resulted in dose-dependent pharmacokinetics (PK) with serum clearance of trastuzumab decreasing with an increasing dose at doses <250 mg. PK modeling of trastuzumab concentration-time data from 7 patients that were administered doses of 250 mg and 500 mg had in a mean halflife of 5.8 days (range 1-32 days).
Intervention: Radiation: Trastuzumab
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Publications * | Malani R, Fleisher M, Kumthekar P, Lin X, Omuro A, Groves MD, Lin NU, Melisko M, Lassman AB, Jeyapalan S, Seidman A, Skakodub A, Boire A, DeAngelis LM, Rosenblum M, Raizer J, Pentsova E. Cerebrospinal fluid circulating tumor cells as a quantifiable measurement of leptomeningeal metastases in patients with HER2 positive cancer. J Neurooncol. 2020 Jul;148(3):599-606. doi: 10.1007/s11060-020-03555-z. Epub 2020 Jun 6. | |||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | ||||
Recruitment Status ICMJE | Completed | |||
Actual Enrollment ICMJE |
34 | |||
Original Estimated Enrollment ICMJE |
24 | |||
Actual Study Completion Date ICMJE | January 20, 2019 | |||
Actual Primary Completion Date | June 20, 2016 (Final data collection date for primary outcome measure) | |||
Eligibility Criteria ICMJE | Inclusion Criteria: ELIGIBILITY CRITERIA
Exclusion Criteria: - Any deviations from the inclusion criteria |
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years and older (Adult, Older Adult) | |||
Accepts Healthy Volunteers ICMJE | No | |||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | |||
Listed Location Countries ICMJE | United States | |||
Removed Location Countries | ||||
Administrative Information | ||||
NCT Number ICMJE | NCT01325207 | |||
Other Study ID Numbers ICMJE | NU 10C03 STU00040150 ( Other Identifier: Northwestern University IRB ) |
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Has Data Monitoring Committee | Yes | |||
U.S. FDA-regulated Product | Not Provided | |||
IPD Sharing Statement ICMJE | Not Provided | |||
Current Responsible Party | Northwestern University | |||
Original Responsible Party | Jeffrey Raizer, MD, Northwestern University | |||
Current Study Sponsor ICMJE | Northwestern University | |||
Original Study Sponsor ICMJE | Same as current | |||
Collaborators ICMJE | Not Provided | |||
Investigators ICMJE |
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PRS Account | Northwestern University | |||
Verification Date | September 2019 | |||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |