ER Positive, Her2 Negative Breast Cancer Patients, Triple Negative Breast Cancer Patients
Conditions
Keywords
Breast Cancer, Neoadjuvant, Her2 negative, Her2 non-overexpressing, Estrogen Receptor Positive, Triple Negative, MM-121, Paclitaxel
Brief summary
To demonstrate whether addition of MM-121 to paclitaxel is more effective than treatment with paclitaxel alone, when administered as part of the neoadjuvant treatment in Her2 negative locally advanced operable breast cancer patients.
Detailed description
This is a multicenter, open-label, randomized, Phase II study of preoperative MM-121 with paclitaxel in HER2-negative breast cancer. Patients will be randomized to receive paclitaxel with or without MM-121 for 12 weeks followed by 4 cycles of doxorubicin plus cyclophosphamide and subsequent surgery.
Interventions
DRUGMM-121
MM-121 IV at 40 mg/mg loading dose on Cycle 1, Week 1 followed by 20 mg/mg weekly for all subsequent doses
DRUGPaclitaxel
Standard dosing of paclitaxel IV, followed by standard dosing of doxorubicin IV plus cyclophosphamide IV, followed by surgery.
Sponsors
Sanofi
Merrimack Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histological confirmation of ER positive, HER2 negative invasive breast cancer (Group 1) or invasive triple-negative breast cancer (Group 2) * Free of metastatic disease * ≥ 18 years old * Female * Had no prior treatment for any cancer * Eligible for treatment with paclitaxel, doxorubicin and cyclophosphamide
Exclusion criteria
* Have a history of severe allergic reactions to paclitaxel or other drugs formulated in Cremaphor® EL * Are pregnant or breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Pathologic Complete Response (pCR) (Rate of pCR) | At time of surgery, an expected average of 24-26 weeks | Pathologic Complete Response was defined as the absence of invasive cancer in the breast and lymph nodes following completion of neoadjuvant systemic therapy and reported according to the current AJCC staging system for neoadjuvant clinical studies. The endpoint was to determine the pathologic Complete Response (pCR) rates associated with weekly treatment of MM-121 plus paclitaxel followed by the combination treatment of doxorubicin plus cyclophosphamide compared with weekly paclitaxel alone followed by the combination treatment of doxorubicin plus cyclophosphamide in patients with human epidermal growth factor receptor 2 (HER2)-negative primary breast cancer. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| HR+: MM-121+ Paclitaxel Hormone-receptor positive (HR+) sub-group randomized to receive:
2 week run-in of MM-121 (20 mg/kg weekly IV infusion over 60 minutes following a 40 mg/kg loading dose), followed by 4 cycles of MM-121 (20 mg/kg weekly) + Paclitaxel (80 mg/kg IV infusion weekly over 60 minutes) for 12 weeks, followed by 4 cycles of doxorubicin and cyclophosphamide (8 weeks) | 67 |
| HR+: Paclitaxel Only Hormone-receptor positive (HR+) sub-group randomized to receive:
Paclitaxel (80 mg/kg IV infusion weekly over 60 minutes) for 12 weeks followed by standard dosing of doxorubicin IV plus cyclophosphamide IV, followed by surgery. | 33 |
| TN: MM-121 + Paclitaxel Triple Negative (TN) patients randomized to receive:
2 week run-in of MM-121 (20 mg/kg weekly IV infusion over 60 minutes following a 40 mg/kg loading dose), followed by 4 cycles of MM-121 (20 mg/kg weekly) + Paclitaxel (80 mg/kg IV infusion weekly over 60 minutes) for 12 weeks, followed by 4 cycles of doxorubicin and cyclophosphamide (8 weeks) | 64 |
| TN: Paclitaxel Triple negative (TN) patients randomized to receive:
Paclitaxel (80 mg/kg IV infusion weekly over 60 minutes) for 12 weeks followed by standard dosing of doxorubicin IV plus cyclophosphamide IV, followed by surgery. | 32 |
| Total | 196 |
Baseline characteristics
| Characteristic | HR+: MM-121+ Paclitaxel | HR+: Paclitaxel Only | TN: MM-121 + Paclitaxel | TN: Paclitaxel | Total |
|---|---|---|---|---|---|
| Age, Continuous | 50.7 years STANDARD_DEVIATION 10.35 | 48.9 years STANDARD_DEVIATION 10.53 | 49.3 years STANDARD_DEVIATION 10.89 | 52.5 years STANDARD_DEVIATION 13.45 | 50.25 years STANDARD_DEVIATION 11.12 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants | 10 Participants | 13 Participants | 3 Participants | 36 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 57 Participants | 22 Participants | 51 Participants | 29 Participants | 159 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 4 Participants | 11 Participants | 5 Participants | 27 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 5 Participants | 1 Participants | 10 Participants |
| Race (NIH/OMB) White | 57 Participants | 26 Participants | 48 Participants | 26 Participants | 157 Participants |
| Region of Enrollment United States | 67 participants | 33 participants | 64 participants | 32 participants | 196 participants |
| Sex: Female, Male Female | 67 Participants | 33 Participants | 64 Participants | 32 Participants | 196 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Subject of Child-Bearing Potential (Y/N) No | 35 participants | 14 participants | 37 participants | 20 participants | 106 participants |
| Subject of Child-Bearing Potential (Y/N) Yes | 32 participants | 19 participants | 27 participants | 12 participants | 90 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 67 / 67 | 33 / 33 | 64 / 64 | 32 / 32 |
| serious Total, serious adverse events | 14 / 67 | 5 / 33 | 18 / 64 | 5 / 32 |
Outcome results
Primary
Number of Participants With Pathologic Complete Response (pCR) (Rate of pCR)
Pathologic Complete Response was defined as the absence of invasive cancer in the breast and lymph nodes following completion of neoadjuvant systemic therapy and reported according to the current AJCC staging system for neoadjuvant clinical studies. The endpoint was to determine the pathologic Complete Response (pCR) rates associated with weekly treatment of MM-121 plus paclitaxel followed by the combination treatment of doxorubicin plus cyclophosphamide compared with weekly paclitaxel alone followed by the combination treatment of doxorubicin plus cyclophosphamide in patients with human epidermal growth factor receptor 2 (HER2)-negative primary breast cancer.
Time frame: At time of surgery, an expected average of 24-26 weeks
Population: Subjects with evaluable resection.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HR+: MM-121+ Paclitaxel | Number of Participants With Pathologic Complete Response (pCR) (Rate of pCR) | Subjects with no pCR | 59 participants |
| HR+: MM-121+ Paclitaxel | Number of Participants With Pathologic Complete Response (pCR) (Rate of pCR) | Subjects with pCR | 7 participants |
| HR+: Paclitaxel Only | Number of Participants With Pathologic Complete Response (pCR) (Rate of pCR) | Subjects with pCR | 1 participants |
| HR+: Paclitaxel Only | Number of Participants With Pathologic Complete Response (pCR) (Rate of pCR) | Subjects with no pCR | 29 participants |
| TN: MM-121 + Paclitaxel | Number of Participants With Pathologic Complete Response (pCR) (Rate of pCR) | Subjects with no pCR | 32 participants |
| TN: MM-121 + Paclitaxel | Number of Participants With Pathologic Complete Response (pCR) (Rate of pCR) | Subjects with pCR | 24 participants |
| TN: Paclitaxel | Number of Participants With Pathologic Complete Response (pCR) (Rate of pCR) | Subjects with no pCR | 14 participants |
| TN: Paclitaxel | Number of Participants With Pathologic Complete Response (pCR) (Rate of pCR) | Subjects with pCR | 15 participants |