MM-302 Plus Trastuzumab vs. Chemotherapy of Physician's Choice Plus Trastuzumab in HER2-Positive Locally Advanced/Metastatic Breast Cancer Patients

Study Overview
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Brief Summary
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This study is an open label, randomized, multicenter trial of MM-302 plus trastuzumab. The trial is designed to demonstrate whether MM-302 plus trastuzumab is more effective than the chemotherapy of physician's choice (CPC) plus trastuzumab in locally advanced/metastatic HER2-positive breast cancer patients. Patients may not have been previously treated with an anthracycline in any setting. Patients must have received prior treatment with trastuzumab in any setting, have either progressed or are intolerant to ado-trastuzumab emtansine in the metastatic or locally advanced setting, have either progressed or are intolerant to pertuzumab in the metastatic or locally advanced setting or had disease recurrence within 12 months of pertuzumab treatment in the neoadjuvant or adjuvant setting.

Official Title
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A Randomized, Multicenter, Open Label Study of MM-302 Plus Trastuzumab vs. Chemotherapy of Physician's Choice Plus Trastuzumab in Anthracycline Naive Patients With Locally Advanced/Metastatic HER2-Positive Breast Cancer

Conditions
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Breast Cancer, HER2 Positive Breast Cancer

Intervention / Treatment
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* Drug: MM-302
* Drug: Gemcitabine
* Drug: Capecitabine
* Drug: Vinorelbine
* Drug: Trastuzumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have histologically or cytologically confirmed invasive cancer of the breast Patients must have documented locally advanced/metastatic disease, defined by the investigator, which is not amenable to resection with curative intent. Patients must have HER2-positive breast cancer as defined by ASCO/CAP 2013 guidelines that is confirmed by a Sponsor-designated central laboratory Patients must have progressed on, or be intolerant to pertuzumab in the LABC/MBC setting or had disease recurrence within 12 months of pertuzumab treatment in the neoadjuvant or adjuvant setting. Patients must have progressed on, or be intolerant to ado-trastuzumab emtansine in the LABC/MBC setting Patients must have been previously treated with trastuzumab in any setting (which may have been previously administered with or without pertuzumab) ECOG Performance Status of 0 or 1 Exclusion Criteria: Patients who have previously been treated with doxorubicin, liposomal doxorubicin, epirubicin, mitoxantrone, or any other anthracycline derivative Subjects with central nervous system (CNS) metastases, unless they have been treated and are stable without symptoms for 4 weeks after completion of treatment and must be off steroids for at least 4 weeks prior to enrollment Patients with any class of New York Heart Association (NYHA) CHF or heart failure with preserved ejection fraction (HFPEF) Patients with a history of known coronary artery disease or a myocardial infarction within the last 12 months Patients with a known history of serious cardiac arrhythmias requiring treatment (exception: controlled atrial fibrillation, paroxysmal supraventricular tachycardia) Patients who previously discontinued trastuzumab due to unacceptable cardiac toxicity Patients with a history of LVEF decline to below 50% during or after prior trastuzumab/lapatinib or other HER2 directed therapy.

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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MM-302 + trastuzumab<br>MM-302 + trastuzumab | Drug: MM-302<br> <br> Drug: Trastuzumab<br> <br> * Other names: Herceptin;|
| Active Comparator: Chemotherapy of Physician's Choice plus trastuzumab<br>Chemotherapy limited to one of the following: Gemcitabine, Capecitabine or Vinorelbine | Drug: Gemcitabine<br> <br> * Other names: Gemzar;Drug: Capecitabine<br> <br> * Other names: Xeloda;Drug: Vinorelbine<br> <br> Drug: Trastuzumab<br> <br> * Other names: Herceptin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Independently assessed progression-free survival according to modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 |  | Approximately 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Locally assessed progression-free survival according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 |  | Approximately 2 years | 
| Overall Survival |  | Approximately 3 years | 
| Time to Treatment Failure |  | Approximately 2 years | 
| Objective Response Rate based on independent and investigator review of tumor assessments |  | Approximately 2 years | 
| Duration of Response (DoR) based on independent and investigator review of tumor assessments |  | Approximately 2 years | 
| Safety | We will look specifically at the Number of Participants with Adverse Events related to MM-302 as compared to the control arm | Approximately 2 years | 
| Pharmacokinetic exposure of MM-302 | Area Under Curve (AUC) Time Frame: Cycles 1 and 2 - pre-infusion, post-infusion, and 168 hours post-dose. An optional timepoint at 8-96 hours post infusion is included during both cycles as well. | Approximately 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HER2+, HER2-positive, HER2, Locally Advanced Breast Cancer, Metastatic Breast Cancer, trastuzumab, Herceptin, pertuzumab, ado-trastuzumab emtansine, TDM-1, Perjeta, Kadcyla