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

NCT ID: NCT04419181

Last Updated: 2025-10-14

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-08-11
• Study Completion Date: 2027-06-01

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.

Conditions

HER2-positive Breast Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Docetaxel

Intervention Type: DRUG

Dose: 75 mg/m2 q3w

Carboplatin

Intervention Type: DRUG

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

Trastuzumab

Intervention Type: DRUG

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

Pertuzumab

Intervention Type: DRUG

Dose: 840-mg loading dose, 420-mg maintenance dose q3w

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.

Group Type: EXPERIMENTAL

Docetaxel

Intervention Type: DRUG

Dose: 75 mg/m2 q3w

Carboplatin

Intervention Type: DRUG

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

Trastuzumab

Intervention Type: DRUG

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

Pertuzumab

Intervention Type: DRUG

Dose: 840-mg loading dose, 420-mg maintenance dose q3w

Trastuzumab emtansine

Intervention Type: DRUG

Dose: 3.6mg/kg q3w

Interventions

Docetaxel

Dose: 75 mg/m2 q3w

Intervention Type: DRUG

Carboplatin

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

Intervention Type: DRUG

Trastuzumab

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

Intervention Type: DRUG

Pertuzumab

Dose: 840-mg loading dose, 420-mg maintenance dose q3w

Intervention Type: DRUG

Trastuzumab emtansine

Dose: 3.6mg/kg q3w

Intervention Type: DRUG

Other Intervention Names

Taxotere; Paraplatin; Herceptin; Perjeta; TDM1

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

University of Rochester

OTHER

Sponsor Role: lead

Responsible Party

Ajay Dhakal

Assistant Professor - Department of Medicine , Hematology/Oncology (SMD)

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ajay Dhakal, MBBS

Role: PRINCIPAL_INVESTIGATOR

University of Rochester

Locations

University of Rochester Medical Center

Rochester, New York, United States

Countries

United States

Other Identifiers

UBRS20013

Identifier Type: -

Identifier Source: org_study_id