ANG1005 in Breast Cancer Patients With Recurrent Brain Metastases

Study Overview
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Brief Summary
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This is a Phase 2 study to see if an investigational drug, ANG1005, can shrink tumor cells in breast cancer patients with recurrent brain metastases.

Official Title
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A Phase II, Open-Label, Multi-Center Study of ANG1005 in Breast Cancer Patients With Recurrent Brain Metastases

Conditions
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Breast Cancer, Brain Metastases

Intervention / Treatment
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* Drug: ANG1005


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥ 18 years old Breast cancer Recurrent brain metastases from breast cancer At least one radiologically-confirmed and measurable metastatic brain lesion ( ≥ 0.5 cm) Neurologically stable Karnofsky Performance Status (KPS) score ≥ 70 Adequate hematology and serum chemistry laboratory test results Expected survival of ≥ 3 months Exclusion Criteria: Prior treatment with ANG1005/GRN1005 Evidence of symptomatic intracranial hemorrhage Pregnancy or lactation Inadequate bone marrow reserve Any evidence of severe or uncontrolled diseases Patients with the presence of an infection including abscess or fistulae, or known infection with hepatitis B or C or HIV History of interstitial lung disease or evidence of clinically significant interstitial lung disease Severe cardiac conduction disturbance Central nervous system (CNS) disease requiring immediate neurosurgery intervention Known severe hypersensitivity or allergy to paclitaxel or any of its components

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ANG1005<br>Participants received ANG1005 intravenously (IV) at a dose of 600 mg/m^2 on Day 1 of each 21-day cycle. ANG1005 will be administered for up to a maximum of one year, or until disease progression or adverse events (AE) that are not tolerated. | Drug: ANG1005<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intracranial objective response rate (iORR) |  | Upon enrollment through end of study period (1 year after last patient is enrolled) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of intracranial objective response |  | Upon enrollment through end of study period (1 year after last patient is enrolled) | 
| Median intracranial progression-free survival (PFS) |  | Upon enrollment through end of study period (1 year after last patient is enrolled) | 
| Intracranial PFS rates at 3, 6 and 12 months |  | Upon enrollment through end of study period (1 year after last patient is enrolled) | 
| 6-month overall survival (OS) rate |  | Upon enrollment through end of study period (1 year after last patient is enrolled | 
| Extracranial objective response rate (eORR) and duration of response |  | Upon enrollment through end of study period (1 year after last patient is enrolled | 
| Number of Patients with adverse events |  | Upon enrollment through end of study period (1 year after last patient is enrolled | 
| Plasma pharmacokinetics of ANG1005 | To determine the drug concentration and distribution in the plasma. (AUC, Cmax, T1/2) | On Day 1 of Cycles 1 and 3 | 
| Intracranial ORR by modified Response Assessment in Neuro-Oncology (RANO) criteria |  | Upon enrollment through end of study period (1 year after last patient is enrolled) | 
| Intracranial clinical benefit rate (iCBR) at 3 and 6 months |  | Upon enrollment through end of study period (1 year after last patient is enrolled) | 
| Potential immunogenicity of ANG1005 |  | 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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Targeted therapy, ANG1005, GRN1005, Low-density lipoprotein receptor-related protein (LRP-1), Breast cancer, Brain metastases, Brain tumor, Blood-brain barrier, Trastuzumab, Herceptin, Paclitaxel, Taxol, Breast cancer with brain metastases, Triple Negative, Triple negative breast cancer (TNBC), Herceptin 2 (HER2)-positive, HER2-negative, Metastatic brain tumors