Brief Summary
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.
Brief Title
MM-302 Plus Trastuzumab vs. Chemotherapy of Physician's Choice Plus Trastuzumab in HER2-Positive Locally Advanced/Metastatic Breast Cancer Patients
Categories
Completion Date
Completion Date Type
Estimated
Conditions
Breast Cancer
HER2 Positive Breast Cancer
Eligibility Criteria
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.
* 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.
Inclusion Criteria
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
* 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
Gender
All
Gender Based
false
Keywords
HER2-positive
HER2+
HER2
Locally Advanced Breast Cancer
Metastatic Breast Cancer
trastuzumab
Herceptin
pertuzumab
ado-trastuzumab emtansine
TDM-1
Perjeta
Kadcyla
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Estimated
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT02213744
Org Class
Industry
Org Full Name
Merrimack Pharmaceuticals
Org Study Id
MM-302-02-02-03
Overall Status
Terminated
Phases
Phase 2
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
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
Primary Outcomes
Outcome Measure
Independently assessed progression-free survival according to modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
Outcome Time Frame
Approximately 2 years
Secondary Outcomes
Outcome Time Frame
Approximately 2 years
Outcome Measure
Locally assessed progression-free survival according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
Outcome Time Frame
Approximately 3 years
Outcome Measure
Overall Survival
Outcome Time Frame
Approximately 2 years
Outcome Measure
Time to Treatment Failure
Outcome Time Frame
Approximately 2 years
Outcome Measure
Objective Response Rate based on independent and investigator review of tumor assessments
Outcome Time Frame
Approximately 2 years
Outcome Measure
Duration of Response (DoR) based on independent and investigator review of tumor assessments
Outcome Description
We will look specifically at the Number of Participants with Adverse Events related to MM-302 as compared to the control arm
Outcome Time Frame
Approximately 2 years
Outcome Measure
Safety
Outcome Description
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.
Outcome Time Frame
Approximately 2 years
Outcome Measure
Pharmacokinetic exposure of MM-302
Start Date
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Joseph Sparano
Investigator Email
jsparano@montefiore.org
Investigator Phone
718-405-8404