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

A Feasibility Study of De-escalation of Chemotherapy in Patients With Early-Stage HER2 Positive Breast Cancer

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.

Study Overview

• Status: Suspended
• Conditions: HER2-positive Breast Cancer
• Intervention / Treatment: Drug: Docetaxel; Drug: Carboplatin; Drug: Trastuzumab; Drug: Pertuzumab; Drug: Trastuzumab emtansine

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.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ajay Dhakal, MBBS; Phone Number: 585-275-5863; Email: Ajay_Dhakal@urmc.rochester.edu

Study Locations

• United States
  • New York
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pathologic complete response (pCR); Participants will receive four cycles of TCHP [docetaxel (Taxotere®), carboplatin, trastuzumab (Herceptin®), pertuzumab], followed by surgery. Participants who achieve pathologic complete response will receive infusions of trastuzumab every 3 weeks for a total of 12 cycles/infusions.	Drug: Docetaxel; Dose: 75 mg/m2 q3w; Other Names: Taxotere; Drug: Carboplatin; Dose: area under the concentration-time curve [AUC] 6 q3w; Other Names: Paraplatin; Drug: Trastuzumab; Dose: 8-mg/kg loading dose, 6-mg/kg maintenance dose q3w; Other Names: Herceptin; Drug: Pertuzumab; Dose: 840-mg loading dose, 420-mg maintenance dose q3w; Other Names: Perjeta
Experimental: Residual Disease; Participants will receive four cycles of TCHP [docetaxel (Taxotere®, carboplatin, trastuzumab (Herceptin®), pertuzumab], followed by surgery. Participants who have residual disease may be offered two more cycles of TCHP in the adjuvant settings (optional) per treating oncologist's discretion and then will receive infusion of Trastuzumab Emtansine (TDM1) plus pertuzumab every three weeks for a total of 12 cycles/infusions.	Drug: Docetaxel; Dose: 75 mg/m2 q3w; Other Names: Taxotere; Drug: Carboplatin; Dose: area under the concentration-time curve [AUC] 6 q3w; Other Names: Paraplatin; Drug: Trastuzumab; Dose: 8-mg/kg loading dose, 6-mg/kg maintenance dose q3w; Other Names: Herceptin; Drug: Pertuzumab; Dose: 840-mg loading dose, 420-mg maintenance dose q3w; Other Names: Perjeta; Drug: Trastuzumab emtansine; Dose: 3.6mg/kg q3w; Other Names: TDM1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	One year from the breast cancer surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathologic Complete Response rate	Assess the pCR rate after four cycles (12 weeks) of TCHP.	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.	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	Two years from the breast cancer surgery

Collaborators and Investigators

• Sponsor: University of Rochester
• Investigators: Principal Investigator: Ajay Dhakal, MBBS, University of Rochester

Study record dates

Study Major Dates

• Study Start (Estimated): August 11, 2024
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: June 1, 2020
• First Submitted That Met QC Criteria: June 4, 2020
• First Posted (Actual): June 5, 2020

Study Record Updates

• Last Update Posted (Actual): October 6, 2023
• Last Update Submitted That Met QC Criteria: October 3, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: HER2-positive Breast Cancer; De-escalation
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Immunoconjugates; Immunotoxins; Docetaxel; Carboplatin; Trastuzumab; Maytansine; Ado-Trastuzumab Emtansine; Pertuzumab
• Other Study ID Numbers: UBRS20013

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes