Paclitaxel + Trastuzumab + Pertuzumab as Pre-Op for Inflammatory BrCa
|ClinicalTrials.gov Identifier: NCT01796197|
Recruitment Status : Active, not recruiting
First Posted : February 21, 2013
Last Update Posted : February 12, 2018
This research study is a Phase II clinical trial, which tests the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific cancer. In this study, paclitaxel and trastuzumab are being combined with pertuzumab which is "investigational" for the preoperative treatment of inflammatory breast cancer. Trastuzumab is given for a total of 12 months for the treatment of HER2 positive breast cancer. This study also adds pertuzumab to trastuzumab so that both drugs are given for a total of 12 months; this combination is also "investigational".
"Investigational" means that pertuzumab is being studied. It also means that although the FDA has approved pertuzumab for preoperative use to treat breast cancer, it has not been thoroughly studied in combination with paclitaxel and trastuzumab for preoperative treatment of inflammatory breast cancer. It has been FDA approved for specific use in advanced breast cancer that is HER2 positive.
Pertuzumab is an antibody, which is a protein that attacks a foreign substance is the body. Pertuzumab blocks the function of the HER2 protein like trastuzumab does. However, pertuzumab binds to a different part of the HER2 receptor and stops cancer cells from growing. This drug has been used in the treatment of advanced breast cancer that is HER2 positive, and has been combined with trastuzumab and chemotherapy in those studies. Information from those other research studies suggests that pertuzumab may help to kill the cancer cells in the breast and enable you to undergo a mastectomy. The addition of pertuzumab may also help reduce the chance of cancer recurrence.
In this research study, we are combining pertuzumab with paclitaxel and trastuzumab as preoperative therapy and will determine the response of the cancer remaining in the breast at the time of mastectomy. In addition, we are combining trastuzumab with pertuzumab for a total of 12 months and we are looking to see whether the combination reduces the chance that the cancer will return.
Another goal of this research study is to determine whether we can develop a way to identify tumors that will respond well to this study treatment. We will do research tests on your tumor tissue before, during and after study treatment. These tests may help doctors understand how the study treatment may work to treat your type of breast cancer. In the future, these tests may help us find ways to help match patients with the drugs most likely to work against their specific tumors before treatment begins.
|Condition or disease||Intervention/treatment||Phase|
|Breast Cancer||Drug: Trastuzumab Drug: Pertuzumab Drug: Paclitaxel Drug: Doxorubicin Drug: Cyclophosphamide Procedure: Mastectomy Radiation: Radiation Therapy||Phase 2|
Show Detailed Description
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||23 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase II Trial of Paclitaxel Combined With Trastuzumab and Pertuzumab as Pre-Operative Therapy for Inflammatory Breast Cancer|
|Study Start Date :||March 2013|
|Estimated Primary Completion Date :||June 2018|
|Estimated Study Completion Date :||March 2020|
U.S. FDA Resources
Experimental: Treatment Arm
Run in phase: Trastuzumab IV 4 mg/kg, Pertuzumab IV 840 mg Pre-op phase: Trastuzumab IV 2 mg/kg weekly, Paclitaxel 80 mg/m2 IV weekly x 16 doses. Starting Day 21 (week 4) continue trastuzumab and paclitaxel as above and add Pertuzumab 420 mg IV every 3 weeks during 16 doses of paclitaxel administration. After completing 16 doses of Paclitaxel, Trastuzumab (6 mg/kg IV) and Pertuzumab 420 mg IV may be continued every 3 weeks until surgery
Modified Radical Mastectomy
Option 1: Adriamycin 60 mg/m2 IV and Cyclophosphamide 600 mg/m2 IV every 2-3 weeks x 4 cycles. Followed by Trastuzumab 8 mg/kg and Pertuzumab 840 IV load; followed by Trastuzumab 6 mg/kg every and Pertuzumab 420 mg IV every 3 weeks to complete 12 months of HER2-directed therapy
Option 2: Continue Trastuzumab 6 mg/kg and Pertuzumab 420 mg every 3 weeks to complete 12 months of HER2-directed therapy
|Drug: Trastuzumab Drug: Pertuzumab Drug: Paclitaxel Drug: Doxorubicin Drug: Cyclophosphamide Procedure: Mastectomy Radiation: Radiation Therapy|
- Pathologic complete response rate [ Time Frame: 2 years ]To determine pathologic complete response (pCR) rate after preoperative therapy with combination paclitaxel (T), trastuzumab (H) and pertuzumab (P) in HER2+ inflammatory breast cancer
- Assess residual cancer burden [ Time Frame: 2 years ]To assess the residual cancer burden (RCB) after preoperative therapy with combination paclitaxel (T), trastuzumab (H) and pertuzumab (P) in HER2+ inflammatory breast cancer.
- Assess toxicity of protocol therapy [ Time Frame: 2 years ]To assess the toxicity of protocol therapy, including clinically-significant CHF
- Determine efficacy of therapy [ Time Frame: 2 years ]To determine the efficacy of therapy defined as disease-free survival (DFS), time to treatment failure (TTF), and overall survival (OS)
- Assess microarray analysis on pre-treatment biopsy specimens [ Time Frame: 2 years ]To assess microarray analysis on pre-treatment breast cancer biopsy specimens using PAM50 to correlate the intrinsic subtype with pCR
- Assess microarray analysis on residual disease [ Time Frame: 2 years ]To assess microarray analysis on residual disease within the breast accessed at the time of mastectomy and by using PAM50 to correlate the intrinsic subtype of the resistance clone with residual disease
- Identify early adaptive responses [ Time Frame: 2 years ]To identify early adaptive responses that are associated with resistance to HER2 directed therapies, i.e., trastuzumab and pertuzumab, but analyzing breast tissue specimens obtained 8 days after exposure to only HER2 directed treatment
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01796197
|United States, Massachusetts|
|Brigham and Women's Hospital|
|Boston, Massachusetts, United States, 02215|
|Dana-Farber Cancer Institute|
|Boston, Massachusetts, United States, 02215|
|United States, Michigan|
|University of Michigan|
|Ann Arbor, Michigan, United States, 48109|
|Principal Investigator:||Beth Overmoyer, MD||Dana-Farber Cancer Institute|