Intrathecal Trastuzumab for Leptomeningeal Metastases in HER2+ Breast Cancer
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT01325207|
Recruitment Status : Active, not recruiting
First Posted : March 29, 2011
Last Update Posted : December 21, 2017
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:||Single Group 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 :||April 2011|
|Estimated Primary Completion Date :||March 2018|
|Estimated Study Completion Date :||March 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
- 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.
- Determine response to IT trastuzumab: radiological, cytological and clinical. [ Time Frame: A baseline enhanced MRI of the brain and spine within 14 days of registration. The first follow up MRI of the brain and spine will be done after 4 weeks then every 6-8 weeks +/- 3 days for each ]
A baseline MRI of the brain and spine within 14 days of registration. Follow up MRI of the brain and spine,at 4 weeks then every 6-8 weeks.
CT chest/abdomen/pelvis is optional but will be ordered if needed to assess systemic disease and any response.
- 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|