Feasibility of Chemotherapy De-escalation in Early-Stage HER2 Positive Breast Cancer

Phase 2WithdrawnNCT04419181

University of Rochester

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Conditions

HER2-positive Breast Cancer

Interventions

DocetaxelDRUG

Dose: 75 mg/m2 q3w

CarboplatinDRUG

Dose: area under the concentration-time curve \[AUC\] 6 q3w

TrastuzumabDRUG

Dose: 8-mg/kg loading dose, 6-mg/kg maintenance dose q3w

Pertuzumab

Eligibility

Sex: FEMALEMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (1)

University of Rochester Medical Center

Rochester, New York, United States

Outcomes

Primary Outcomes

One Year Invasive Disease-Free Survival

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.

Time frame: One year from the breast cancer surgery

Secondary Outcomes

Pathologic Complete Response rate

Assess the pCR rate after four cycles (12 weeks) of TCHP.

Time frame: 12 weeks from start of treatment

Toxicity of chemo and HER2 therapies

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.

Time frame: One year from the start of treatment

Two Year Invasive Disease-Free Survival

Two year invasive disease-free survival (IDFS) of participants with pCR and participants with residual disease

Time frame: Two years from the breast cancer surgery

Data from ClinicalTrials.gov

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