HER2-positive Breast Cancer
Conditions
Keywords
HER2-positive Breast Cancer, De-escalation
Brief summary
The main purpose of this research study is to find out if de-escalation of chemotherapy before surgery followed by a selective escalation of adjuvant targeted therapies are efficacious and tolerable in early-stage HER2 positive breast cancer.
Detailed description
Assess the feasibility of four cycles of neoadjuvant Docetaxel Carboplatin Trastuzumab and Pertuzumab (TCHP) in women with early-stage (local/locally advanced) HER2+ breast cancer with a selective escalation of targeted HER2 directed therapy in the high risk group in the adjuvant setting. Participants with any residual disease after four cycles of TCHP will receive Trastuzumab Emtansine (TDM1) plus Pertuzumab while those with complete pathological response will receive Trastuzumab in the adjuvant settings.
Interventions
DRUGDocetaxel
Dose: 75 mg/m2 q3w
DRUGCarboplatin
Dose: area under the concentration-time curve \[AUC\] 6 q3w
DRUGTrastuzumab
Dose: 8-mg/kg loading dose, 6-mg/kg maintenance dose q3w
DRUGPertuzumab
Dose: 840-mg loading dose, 420-mg maintenance dose q3w
DRUGTrastuzumab emtansine
Dose: 3.6mg/kg q3w
Sponsors
University of Rochester
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Participants will be assigned to an arm of the trial based on their outcomes after surgery.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Women ≥18 years of age * Biopsy proven HER2+ early breast cancer * ECOG performance status 0-1 * Should be a candidate for neoadjuvant chemotherapy using standard guidelines of tumor size of 2cm or more and /or axillary lymph node-positive disease. * Adequate cardiac, bone marrow, kidney, and liver functions per treating physician's discretion. * Women of childbearing potential who are sexually active must agree to use highly effective methods of contraception during treatment and for three weeks after the last dose of chemotherapy or anti-HER2 therapy. The women currently using hormonal contraceptives must agree to change to an alternative highly effective method of contraception * Willingness and ability to comply with study and follow-up procedures and give written informed consent.
Exclusion criteria
* Any evidence of stage IV breast cancer * Participant deemed unsuitable for clinical trial enrolment by treating physician based on the participants' compliance, location and commute requirements, or tolerance of therapies involved * Any invasive malignancy within the last two years of study enrollment except for adequately treated basal cell carcinoma, squamous cell carcinoma, or non-melanoma skin cancer. * Women who are pregnant or breastfeeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| One Year Invasive Disease-Free Survival | One year from the breast cancer surgery | The study will be considered feasible if the researchers observe the invasive disease free survival (IDFS) estimate at one year to be 90% or more among those who achieved a pCR, or if the researchers observe the IDFS estimate at one year to be 85% or more among those who had residual disease. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pathologic Complete Response rate | 12 weeks from start of treatment | Assess the pCR rate after four cycles (12 weeks) of TCHP. |
| Toxicity of chemo and HER2 therapies | One year from the start of treatment | Evaluate toxicity associated with neoadjuvant and adjuvant chemo and/or HER2 directed therapies. Percentage of grade 1 to grade 5 toxicities will be assessed during the neo-adjuvant TCHP therapy for all participants. Percentage of grade 1 to grade 5 toxicities will be assessed with adjuvant trastuzumab therapy for the cohort with pathological complete response, and with optional adjuvant TCHP therapy and adjuvant TDM1 + pertuzumab therapy for the residual disease cohort. Toxicity data will be obtained based on the clinical assessment of the participants by the investigators and based on laboratory data. |
| Two Year Invasive Disease-Free Survival | Two years from the breast cancer surgery | Two year invasive disease-free survival (IDFS) of participants with pCR and participants with residual disease |
Countries
United States
Outcome results
None listed