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
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.
|Condition or disease||Intervention/treatment||Phase|
|Breast Cancer||Radiation: Trastuzumab||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||34 participants|
|Intervention Model:||Sequential Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I/II Dose Escalation Trial to Assess Safety of Intrathecal Trastuzumab for the Treatment of Leptomeningeal Metastases in HER2 Positive Breast Cancer|
|Study Start Date :||August 1, 2011|
|Actual Primary Completion Date :||June 20, 2016|
|Actual Study Completion Date :||January 20, 2019|
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).
Trastuzumab will be administered twice per week for 4 weeks, then once per week for 4 weeks, and then every 2 weeks
- Number of Dose Limiting Toxicities (DLT) of IT Trastuzumab in Sequential Cohorts of Escalating Doses for Patients With Leptomeningeal Metastases in HER2+ Breast Cancer. [ Time Frame: From treatment initiation through the first 4 weeks of treatment. ]
Patients will be treated using a standard 3+3 dose-escalation design for cohorts 1 and 2. This will be followed by an accelerated phase I for cohorts 3 and 4, and then a standard 3 + 3 for the 5th cohort. In the accelerated phase (cohorts 3 and 4), 1 patient will be enrolled per cohort; if a toxicity is seen in that patient then the cohort would be expanded to 6 patients to allow for 1/6 patients per cohort to have a dose limiting toxicity (DLT) before dose escalation. Cohort 5 will enroll a total of 6 patients regardless of the toxicity experienced in patient one. However, if 2 or more DLTs are observed in cohort 5, cohort 4 will be reopened to enroll of a total of 6 patients. Whatever dose is ultimately declared the MTD should have 6 patients total. If 1/6 DLTs are seen in cohort 5 that will be considered the MTD.
Dosing is as follows:
Cohort 1-10 mg IT Cohort 2-20 mg IT Cohort 3-40 mg IT Cohort 4-60 mg IT Cohort 5-80 mg IT
- Best Response to IT Trastuzumab: Radiological, Cytological and Clinical in Treatment With Intrathecal Trastuzumab for Patients With Leptomeningeal Metastases in HER2+ Breast Cancer. [ Time Frame: Baseline then at 4 weeks, 8 weeks and then every 8 weeks +/- 3 days, until disease progression or toxicity,range of cycles completed 1-22 cycles where 1 cycle = 28 days. ]Best response will be assessed using a combination CSF cytology assessment, radiographic assessment and clinical function assessments. Best response will be defined as the best response seen during treatment as compared to baseline that is confirmed on subsequent response assessment.
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01325207
|United States, California|
|University of California San Francisco (UCSF)|
|San Francisco, California, United States, 94143-1710|
|United States, Illinois|
|Chicago, Illinois, United States, 60611|
|United States, Massachusetts|
|Tufts Medical Center|
|Boston, Massachusetts, United States, 02111|
|Dana Farber Cancer Institute|
|Boston, Massachusetts, United States, 02215|
|United States, New York|
|New York, New York, United States, 10032|
|Memorial Sloan-Kettering Cancer Center|
|New York, New York, United States, 10065|
|United States, Rhode Island|
|Rhode Island Hospital|
|Providence, Rhode Island, United States, 02903|
|United States, Texas|
|Austin, Texas, United States, 78705|
|Principal Investigator:||Jeffrey Raizer, MD||Northwestern University|