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

Study Overview
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Brief Summary
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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).

Detailed Description
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Please see Brief Summary section.

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

Conditions
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Breast Cancer, Brain Metastases

Intervention / Treatment
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* Drug: GRN1005
* Drug: Trastuzumab
* Drug: 18F-FLT


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Age ≥ 18 years Histologically or cytologically-documented breast cancer (HER2 status and ER/PgR status must be known) Brain metastasis from breast cancer with or without prior WBRT 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) 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 KPS ≥ 70% Completed WBRT for intra-cranial lesions ≥ 28 days prior to first dose Key Exclusion Criteria: NCI CTCAE v4.0 Grade ≥ 2 neuropathy CNS disease requiring immediate neurosurgical intervention (e.g., resection, shunt placement, etc.) Known leptomeningeal disease

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GRN1005<br>GRN1005 alone in HER2- MBC patients with brain mets. 18F-FLT may also be administered to this arm (if patient enrolled at NCI) | Drug: GRN1005<br>* 550 mg/m2 IV every 3 weeks<br>* Other names: ANG1005;Drug: 18F-FLT<br>* 5 mCi of 18F-FLT IV during Screening and during Cycle 1<br>* Other names: 18F-fluorothymidine;|
| Experimental: GRN1005 with trastuzumab<br>GRN1005 in combination with trastuzumab in MBC patients with brain mets 18F-FLT may also be administered to this arm (if patient enrolled at NCI) | Drug: GRN1005<br>* 550 mg/m2 IV every 3 weeks<br>* Other names: ANG1005;Drug: Trastuzumab<br>* 2 mg/kg IV every week or 6 mg/kg IV every 3 weeks per investigator choice<br>* Other names: Herceptin;Drug: 18F-FLT<br>* 5 mCi of 18F-FLT IV during Screening and during Cycle 1<br>* Other names: 18F-fluorothymidine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intra-cranial objective response rate in breast cancer patients with brain metastasis |  | Upon enrollment through end of study period (1 year after last patient is enrolled) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with adverse events as a measure of safety and tolerability of GRN1005 alone or in combination with Trastuzumab |  | Upon enrollment through end of study period (1 year after last patient is enrolled) | 
| Intra-cranial objective response duration |  | Upon enrollment through end of study period (1 year after last patient is enrolled) | 
| 3-month intra-cranial progression-free survival |  | Upon enrollment through end of study period (1 year after last patient is enrolled) | 
| Six month overall survival (OS) |  | Upon enrollment through end of study period (1 year after last patient is enrolled) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GRN1005, ANG1005, Peptide-Drug Conjugate (PDC), LRP-1, Targeted Therapy, Breast Cancer, Brain Metastases, Brain Tumor, Blood Brain Barrier, Trastuzumab, Herceptin, Paclitaxel, Taxol, Breast cancer with brain metastases