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

NCT04419181 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: UBRS20013
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

HER2-positive Breast Cancer

Keywords

HER2-positive Breast Cancer; De-escalation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Pathologic Complete Response rate

  12 weeks from start of treatment

• Toxicity of chemo and HER2 therapies

  One year from the start of treatment

• Two Year Invasive Disease-Free Survival

  Two years from the breast cancer surgery

Study Arms (2)

Pathologic complete response (pCR)

EXPERIMENTAL

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; Drug: Carboplatin; Drug: Trastuzumab; Drug: Pertuzumab

Residual Disease

EXPERIMENTAL

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; Drug: Carboplatin; Drug: Trastuzumab; Drug: Pertuzumab; Drug: Trastuzumab emtansine

Interventions

Docetaxel DRUG

Dose: 75 mg/m2 q3w

Also known as: Taxotere

Pathologic complete response (pCR); Residual Disease

Carboplatin DRUG

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

Also known as: Paraplatin

Pathologic complete response (pCR); Residual Disease

Trastuzumab DRUG

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

Also known as: Herceptin

Pathologic complete response (pCR); Residual Disease

Pertuzumab DRUG

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

Also known as: Perjeta

Pathologic complete response (pCR); Residual Disease

Trastuzumab emtansine DRUG

Dose: 3.6mg/kg q3w

Also known as: TDM1

Residual Disease

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Rochester: lead

Study Sites (1)

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

MeSH Terms

Interventions

Docetaxel; Carboplatin; Trastuzumab; pertuzumab; Ado-Trastuzumab Emtansine

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Maytansine; Macrolides; Lactones; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Study Officials

• Ajay Dhakal, MBBS

  University of Rochester

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor - Department of Medicine , Hematology/Oncology (SMD)

Model Details: Participants will be assigned to an arm of the trial based on their outcomes after surgery.

Study Record Dates

• First Submitted: June 1, 2020
• First Posted: June 5, 2020
• Study Start: August 11, 2025
• Primary Completion: June 1, 2026
• Study Completion (Estimated): June 1, 2027
• Last Updated: October 14, 2025

Record last verified: 2025-10

Locations

US (1)