Trial of Exemestane +/- MM-121 in Postmenopausal Women With Locally Advanced or Metastatic Estrogen Receptor Positive and/or Progesterone Receptor Positive Her2 Negative Breast Cancer

Study Overview
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Brief Summary
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To determine whether the combination MM-121 + Exemestane in ER+ and/or PR+ breast cancer patients is more effective than Exemestane alone

Detailed Description
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The study is a double-blind, randomized Phase 2 trial of Exemestane +/- MM-121. The trial is designed to demonstrate whether MM-121 + Exemestane is more effective than Exemestane alone in ER+ and/or PR+ and Her2 negative breast cancer patients that have failed first-line anti-estrogen therapy in the locally advanced or metastatic setting and patients that have progressed during (or within 6 months of completing) adjuvant treatment with a non-steroidal aromatase inhibitor (AI)and/or tamoxifen. Patients will be treated until radiologic or clinical progression of their disease is documented. Local radiologist and/or PI assessment is accepted.

Official Title
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A Randomized Double-Blind Phase 2 Trial of Exemestane +/- MM-121 in Postmenopausal Women With Locally Advanced or Metastatic Estrogen Receptor Positive (ER+) and/or Progesterone Receptor Positive (PR+) Her2 Negative Breast Cancer

Conditions
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Her2 Negative Breast Cancer Patients

Intervention / Treatment
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* Drug: MM-121
* Drug: Placebo
* Drug: Exemestane


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Locally advanced or metastatic breast cancer Histologically or cytologically confirmed ER+ and/or PgR+ and Her2 negative breast cancer ≥ 18 years of age Exclusion Criteria: Received prior treatment with exemestane Extensive visceral disease (rapidly progressive, life-threatening metastases, including symptomatic lymphangitic metastases) Symptomatic CNS disease

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MM-121 (SAR256212) + exemestane<br> | Drug: MM-121<br>* MM-121 (40mg/kg loading dose week 1, then 20 mg/kg weekly) administered over 60 minutes as an intravenous infusion once per week<br>* Other names: SAR256212;Drug: Exemestane<br>* Exemestane (25 mg) administered orally once per day<br>* Other names: Aromasin;|
| Placebo Comparator: Placebo + exemestane<br> | Drug: Placebo<br>* Placebo (histidine solution) administered over 60 minutes as an intravenous infusion once per week and exemestane (25 mg) administered orally once per day<br>Drug: Exemestane<br>* Exemestane (25 mg) administered orally once per day<br>* Other names: Aromasin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | To determine whether MM-121 + exemestane was more effective than placebo + exemestane in prolonging progression-free survival. PFS was a time to event measure, and progression of disease is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Progression free survival was defined as the number of months from the date of randomization to the date of death or progression. If neither death nor progression was observed during the study, PFS data was censored at the last non-progressive disease valid tumor assessment unless the patient was discontinued due to symptomatic deterioration. If this occurred, the patient was counted as having progressive disease (PD). | Time from first dose to date of progression, the longest time frame of 79.1 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | To determine whether MM-121 + exemestane is more effective than placebo + exemestane in prolonging overall survival. This was a time-to-event analysis of time from first dose to date of death. | Time from first dose to date of death, over approximately 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast Cancer, Her2 negative, Estrogen Receptor Positive, Progesterone Receptor Positive, MM-121, Exemestane, Postmenopausal Women