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Intrathecal Pertuzumab and Trastuzumab in Patients With New Untreated Asymptomatic or Low Symptomatic Brain Metastasis in HER2 Positive Breast Cancer

2015-11-08 17:59:51 | BioPortfolio

Summary

The purpose of this research study is to determine how well pertuzumab and trastuzumab works in treating breast cancer that has spread to the brain. Pertuzumab and trastuzumab are treatments that stop breast cancer cells from growing abnormally by inhibiting (or blocking) members of a family of proteins that include Human Epidermal Growth Factor Receptor 2 (HER2).

Pertuzumab and trastuzumab have been found to be very effective for HER2-positive breast cancer and are FDA approved for treatment of metastatic breast cancer outside of the brain when given through the vein. This suggests that pertuzumab and trastuzumab may help shrink or stabilize HER2-positive breast cancer that has spread to the brain in this research study.

In this research study, the investigators are looking to see whether pertuzumab and trastuzumab will work to decrease the size of or stabilize breast cancer that has spread to the brain.

Description

Intrathecal administration of pertuzumab and trastuzumab will occur via lumbar puncture under fluoroscopic guidance by interventional radiology at Duke University Medical Center. If pharmacokinetics are needed during the lumbar puncture at that cycle, 3 mL of CSF will be collected (a minimum of 2 mL of CSF is needed for PK testing). If pharmacokinetics are not needed during the lumbar puncture at that cycle, 3 mL of CSF will be removed to allow for injection of an equivalent volume of intrathecal therapy. Once the CSF is removed, the intrathecal pertuzumab and trastuzumab will be administered using aseptic technique.

Patients will be treated using a 3+3 dose-escalation design. Patients will not be accrued to the next cohort (dose escalation) until at least one patient on the previous cohort has been followed for six weeks. If a dose limiting toxicity (DLT) is seen in a patient then the cohort will be expanded by an additional 3 patients to allow for 1 in 6 patients per cohort to have a DLT before dose escalation. Dose limiting toxicity will be assessed weekly during the first six weeks of the treatment.

Patients will be treated weekly for the first six weeks and then every 3 weeks (q21 days). Once the maximum tolerated dose is reached, an additional 12 patients will be enrolled in the cohort at the maximum tolerated dose. The maximum number of enrolled patients is 36. Dosing is as follows: Cohort 1 - 80mg IT trastuzumab, 10mg IT pertuzumab, cohort 2 - 80mg IT trastuzumab, 20mg IT pertuzumab, cohort 3 - 80mg IT trastuzumab, 40mg IT pertuzumab, cohort 4 - 80mg IT trastuzumab, 80mg IT pertuzumab. If the lowest dose level is found to be too toxic, the trial will stop without finding a maximum tolerated dose.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Conditions

HER2 Positive Untreated Metastatic Breast Cancer

Intervention

Pertuzumab, Trastuzumab

Location

Duke University Medical Center
Durham
North Carolina
United States
27710

Status

Not yet recruiting

Source

Duke University

Results (where available)

View Results

Links

Published on BioPortfolio: 2015-11-08T17:59:51-0500

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