ANG1005 in Leptomeningeal Disease From Breast Cancer

Study Overview
=================
Brief Summary
-----------------
This is an open-label Phase 3 study to see if ANG1005 can prolong survival compared to a Physician Best Choice control in HER2-negative breast cancer patients with newly diagnosed leptomeningeal disease and previously treated brain metastases.

Official Title
-----------------
A Randomized Open-Label, Multi-Center Pivotal Study of ANG1005 Compared With Physician's Best Choice in HER2-Negative Breast Cancer Patients With Newly Diagnosed Leptomeningeal Carcinomatosis and Previously Treated Brain Metastases (ANGLeD)

Conditions
-----------------
Leptomeningeal Carcinomatosis, Leptomeningeal Metastases, Brain Metastases, HER2-negative Breast Cancer

Intervention / Treatment
-----------------
* Drug: ANG1005
* Drug: Physician's Best Choice


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: ≥ 18 years old HER2-negative breast cancer At least 2 months of expected survival Newly diagnosed leptomeningeal carcinomatosis Documented history of brain metastasis that has been previously treated with radiation therapy Neurologically stable Eastern Cooperative Oncology Group performance status grade ≤2 Adequate laboratory test results prior to first dose Patients who are fertile must agree to remain abstinent or use reliable method of birth control Exclusion Criteria: Any prior treatment for leptomeningeal carcinomatosis, except emergency radiotherapy or shunt Prior treatment with ANG1005 Patients who have not had radiotherapy for their brain metastases Evidence of symptomatic intracranial hemorrhage or increased intracranial pressure Patients for whom intrathecal therapy is the most appropriate therapy for leptomeningeal disease Pregnancy or lactation and patients planning to be pregnant during the study Peripheral neuropathy > Grade 2 Evidence of severe or uncontrolled diseases Presence of an infection including abscess or fistulae, or known infection with hepatitis B or C or HIV History of interstitial lung disease Severe conduction disturbance Central nervous system disease requiring immediate neurosurgical intervention Known allergy to paclitaxel or any of its components Contra-indication for contrast-enhanced MRI

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 1:1 randomization to experimental arm and comparator arm
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ANG1005<br>ANG1005 Investigational Drug | Drug: ANG1005<br>* Investigational drug<br>* Other names: paclitaxel trevatide;|
| Active Comparator: Physician's Best Choice<br>One of the protocol specified Physician's Best Choice therapies, assigned by the Investigator prior to randomization: capecitabine or eribulin or high-dose intravenous (IV) methotrexate. | Drug: Physician's Best Choice<br>* Active Comparator: one of 3 pre-determined choices of therapies: capecitabine or eribulin or high-dose IV methotrexate.<br>* Other names: high-dose IV methotrexate.;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | From the date of randomization until death due to any cause, assessed for up to 2 years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Central nervous system progression-free survival |  | From the date of randomization until central nervous system progression, assessed for up to 2 years. | 
| Central nervous system clinical benefit rate at 3, 6 and 12 months |  | At 3, 6 and 12 months. | 
| 6-month and 12-month overall survival rates |  | At 6 and 12 months. | 
| Leptomeningeal carcinomatosis response rate |  | Assessed for up to 2 years from first patient randomised. | 
| Duration of leptomeningeal carcinomatosis response |  | Assessed for up to 2 years from first patient randomised. | 
| Overall survival in triple negative breast cancer patients |  | From the date of randomization until death due to any cause, assessed for up to 2 years. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
ANG1005, Leptomeningeal carcinomatosis, Leptomeningeal disease, Leptomeningeal metastases, Brain metastases, HER2-negative, Breast cancer, Targeted therapy