GRN1005 Alone or in Combination With Trastuzumab in Breast Cancer Patients With Brain Metastases

A Phase II, Multi-center, Open-label Study Evaluating GRN1005 Alone or in Combination With Trastuzumab in Breast Cancer Patients With Brain Metastases

The purpose of this study is to assess the efficacy, safety, and tolerability of GRN1005 in patients with brain metastases from breast cancer. For patients with HER2 positive metastatic breast cancer, GRN1005 will be assessed in combination with Trastuzumab (Herceptin®) as per standard-of-care practice.

In addition, this study will evaluate the ability of 18F-FLT to determine if the amount of change in the uptake in the brain metastases from breast cancer after GRN1005 treatment, correlates with intra-cranial response (for patients enrolled at NCI).

Please see Brief Summary section.

Key Inclusion Criteria:

1. Age ≥ 18 years
2. Histologically or cytologically-documented breast cancer (HER2 status and ER/PgR status must be known)
3. Brain metastasis from breast cancer with or without prior WBRT
4. At least one radiologically-confirmed and measurable metastatic brain lesion (≥ 1.0 cm in the longest diameter) by Gd-MRI of the brain < 14 days prior to first dose (Metastatic brain lesions previously treated with SRS may not be target or non-target lesions)
5. Patients must be neurologically stable: On stable doses of corticosteroids and anticonvulsants (not EIAEDs, including phenytoin, phenobarbitol, carbamazepine, fosphenytoin, primidone, oxcarbazepine) for ≥ 5 days prior to obtaining the baseline Gd-MRI of the brain and ≥ 5 days prior to first dose
6. KPS ≥ 70%
7. Completed WBRT for intra-cranial lesions ≥ 28 days prior to first dose

Key Exclusion Criteria:

1. NCI CTCAE v4.0 Grade ≥ 2 neuropathy
2. CNS disease requiring immediate neurosurgical intervention (e.g., resection, shunt placement, etc.)
3. Known leptomeningeal disease