A Phase II Randomized Trial Evaluating Neoadjuvant Dose-Dense Doxorubicin/Cyclophosphamide Followed by Paclitaxel/Trastuzumab/Pertuzumab (AC THP) and Docetaxel/Carboplatin/Trastuzumab/Pertuzumab (TCHP) For Early Her2Neu Positive Breast Cancer
Overview
- Phase
- Phase 2
- Intervention
- Pertuzumab
- Conditions
- Locally Advanced Breast Cancer
- Sponsor
- Icahn School of Medicine at Mount Sinai
- Enrollment
- 7
- Locations
- 3
- Primary Endpoint
- Number of Participants With Pathologic Complete Response (pCR)
- Status
- Terminated
- Last Updated
- 2 years ago
Overview
Brief Summary
Primary Objective:
• Determination of pathologic complete response (pCR) rates
Secondary Objective:
- Determination of cardiac toxicity as measured by: composite of LVEF, longitudinal strain and troponin.
- Breast conservation rates
- Overall survival
Study Design
-
Approximately 34-74 patients with Her2 positive, Stage II-regional IV breast cancer will be enrolled.
-
Patients will be stratified by ER/PR status.
-
They will be randomized to ddACTHP vs TCHP.
- Initially, 17 patients will be randomly assigned to each treatment arm.
- If 3 or fewer patients have a pCR, then that arm will be terminated and no further patients will be entered on that treatment arm.
- If 4 or more patients obtain a pCR, 20 additional patients (total of 37 patients) will be randomized to that treatment arm.
- If 11 or more patients out of 37 have a pCR, the treatment will be of interest for further study.
Investigators
Aarti S. Bhardwaj
Assistant Professor
Icahn School of Medicine at Mount Sinai
Eligibility Criteria
Inclusion Criteria
- •The patient must have signed and dated an IRB-approved consent form that conforms to federal and institutional guidelines.
- •18 years or older
- •ECOG performance status of 0 or 1
- •Eligible tumors must meet one of the following criteria:
- •Operable (T1c, T2-3, N0-1, M0)
- •Locally advanced (T2-3, N2-3, M0 or T4a-c, any N, M0)
- •Inflammatory breast cancer (T4d, any N, M0)
- •Staging evaluation:
- •History and physical exam, cbc, chemistry profile
- •CT Chest/Abdomen/Pelvis and a bone scan or PET/CT as needed
Exclusion Criteria
- •Patients with a history of decompensated congestive heart failure or an EF \< 55% will be excluded
- •Cardiac disease that would preclude the use of the drugs included in the above regimens. This includes but is not confined to:
- •Active cardiac disease:
- •angina pectoris requiring the use of anti-anginal medication;
- •ventricular arrhythmias except for benign premature ventricular contractions controlled by medication;
- •conduction abnormality requiring a pacemaker;
- •supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication; and
- •clinically significant valvular disease
- •symptomatic pericarditis
- •pulmonary hypertension
Arms & Interventions
ddACTHP
Doxorubicin 60 mg/m2 IV day 1 Cyclophosphamide 600 mg/m2 IV day 1 Pegfilgrastim 6mg SC, day 2 of AC Cycled every 14 days for 4 cycles, followed by, Paclitaxel 80 mg/m2 IV x 1 hour infusion on days 1, 8, and 15 Trastuzumab 8 mg/kg IV day 1, followed by 6mg/kg Pertuzumab loading dose 840 mg IV followed by 420 mg IV every 3 weeks Cycled every 21 days for 4 cycles, followed by, Trastuzumab 6mg/kg every 21 days to complete 1 year
Intervention: Pertuzumab
ddACTHP
Doxorubicin 60 mg/m2 IV day 1 Cyclophosphamide 600 mg/m2 IV day 1 Pegfilgrastim 6mg SC, day 2 of AC Cycled every 14 days for 4 cycles, followed by, Paclitaxel 80 mg/m2 IV x 1 hour infusion on days 1, 8, and 15 Trastuzumab 8 mg/kg IV day 1, followed by 6mg/kg Pertuzumab loading dose 840 mg IV followed by 420 mg IV every 3 weeks Cycled every 21 days for 4 cycles, followed by, Trastuzumab 6mg/kg every 21 days to complete 1 year
Intervention: Trastuzumab
ddACTHP
Doxorubicin 60 mg/m2 IV day 1 Cyclophosphamide 600 mg/m2 IV day 1 Pegfilgrastim 6mg SC, day 2 of AC Cycled every 14 days for 4 cycles, followed by, Paclitaxel 80 mg/m2 IV x 1 hour infusion on days 1, 8, and 15 Trastuzumab 8 mg/kg IV day 1, followed by 6mg/kg Pertuzumab loading dose 840 mg IV followed by 420 mg IV every 3 weeks Cycled every 21 days for 4 cycles, followed by, Trastuzumab 6mg/kg every 21 days to complete 1 year
Intervention: Paclitaxel
ddACTHP
Doxorubicin 60 mg/m2 IV day 1 Cyclophosphamide 600 mg/m2 IV day 1 Pegfilgrastim 6mg SC, day 2 of AC Cycled every 14 days for 4 cycles, followed by, Paclitaxel 80 mg/m2 IV x 1 hour infusion on days 1, 8, and 15 Trastuzumab 8 mg/kg IV day 1, followed by 6mg/kg Pertuzumab loading dose 840 mg IV followed by 420 mg IV every 3 weeks Cycled every 21 days for 4 cycles, followed by, Trastuzumab 6mg/kg every 21 days to complete 1 year
Intervention: Doxorubicin
ddACTHP
Doxorubicin 60 mg/m2 IV day 1 Cyclophosphamide 600 mg/m2 IV day 1 Pegfilgrastim 6mg SC, day 2 of AC Cycled every 14 days for 4 cycles, followed by, Paclitaxel 80 mg/m2 IV x 1 hour infusion on days 1, 8, and 15 Trastuzumab 8 mg/kg IV day 1, followed by 6mg/kg Pertuzumab loading dose 840 mg IV followed by 420 mg IV every 3 weeks Cycled every 21 days for 4 cycles, followed by, Trastuzumab 6mg/kg every 21 days to complete 1 year
Intervention: Cyclophosphamide
TCHP
TCHP (Docetaxel, Carboplatin, Trastuzumab, Pertuzumab, Pegfilgrastim ) institutional practice is to titrate the infusion rate on the initial Paclitaxel dose (40 ml/hr x 5 min, then 80 ml/hr x 5 min, then 120 ml/hr x 10 min, then 200 ml/hr). Subsequent Paclitaxel doses are given over 1 hour.
Intervention: Docetaxel
TCHP
TCHP (Docetaxel, Carboplatin, Trastuzumab, Pertuzumab, Pegfilgrastim ) institutional practice is to titrate the infusion rate on the initial Paclitaxel dose (40 ml/hr x 5 min, then 80 ml/hr x 5 min, then 120 ml/hr x 10 min, then 200 ml/hr). Subsequent Paclitaxel doses are given over 1 hour.
Intervention: Carboplatin
TCHP
TCHP (Docetaxel, Carboplatin, Trastuzumab, Pertuzumab, Pegfilgrastim ) institutional practice is to titrate the infusion rate on the initial Paclitaxel dose (40 ml/hr x 5 min, then 80 ml/hr x 5 min, then 120 ml/hr x 10 min, then 200 ml/hr). Subsequent Paclitaxel doses are given over 1 hour.
Intervention: Trastuzumab
TCHP
TCHP (Docetaxel, Carboplatin, Trastuzumab, Pertuzumab, Pegfilgrastim ) institutional practice is to titrate the infusion rate on the initial Paclitaxel dose (40 ml/hr x 5 min, then 80 ml/hr x 5 min, then 120 ml/hr x 10 min, then 200 ml/hr). Subsequent Paclitaxel doses are given over 1 hour.
Intervention: Pertuzumab
TCHP
TCHP (Docetaxel, Carboplatin, Trastuzumab, Pertuzumab, Pegfilgrastim ) institutional practice is to titrate the infusion rate on the initial Paclitaxel dose (40 ml/hr x 5 min, then 80 ml/hr x 5 min, then 120 ml/hr x 10 min, then 200 ml/hr). Subsequent Paclitaxel doses are given over 1 hour.
Intervention: Pegfilgrastim
TCHP
TCHP (Docetaxel, Carboplatin, Trastuzumab, Pertuzumab, Pegfilgrastim ) institutional practice is to titrate the infusion rate on the initial Paclitaxel dose (40 ml/hr x 5 min, then 80 ml/hr x 5 min, then 120 ml/hr x 10 min, then 200 ml/hr). Subsequent Paclitaxel doses are given over 1 hour.
Intervention: Paclitaxel
Outcomes
Primary Outcomes
Number of Participants With Pathologic Complete Response (pCR)
Time Frame: 2 years
Pathologic complete response (pCR) defined as the absence of any residual invasive cancer on hematoxylin and eosin evaluation of the resected breast specimen and all sampled ipsilateral lymph nodes following completion of neoadjuvant systemic therapy.
Secondary Outcomes
- Number of Participants Alive at the End of the Study(2 years)
- Number of Non-cardiac Toxicities(2 years)
- Number of Participants With Breast Conservation(2 years)
- Number of Cardiac Toxicity Events(2 years)