T-DM1+Pertuzumab in Pre-OP Early-Stage HER2+ BRCA

NCT02326974 | Active Not Recruiting Phase 2 Results DMC

• 1 other identifier: 14-409
• Study Type: interventional
• Target: 164
• Locations: 1 country
• Sites: 4

Brief Summary

This research study is studying a combination of drugs as a possible treatment for breast cancer that has tested positive for a protein called HER2. The names of the study interventions involved in this study are:

• Trastuzumab emtansine (also called T-DM1)
• Pertuzumab

Conditions

HER-2 Positive Breast Cancer; Breast Cancer; Stage II Breast Cancer; Stage III Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Rate of Pathologic Complete Response (pCR) by HER2 Amplification Status Non-Heterogeneous

  The rate of pCR is the percentage of participants with Residual Cancer Burden (RCB)=0 as defined by established guidelines (Symmans et al. JCO 2007; M.D Anderson http://www.mdanderson.org/breastcancer\_RCB). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

  Evaluate upon completion of breast surgery, up to approximately 24 weeks from study enrollment.

Secondary Outcomes (8)

• Rate of Pathologic Complete Response (pCR)

  Evaluate upon completion of breast surgery, up to approximately 24 weeks from study enrollment.

• Hormone Receptor (HR) Status by HER2 Amplification Status

  Day 0 (baseline/at study entry)

• Median Disease-Free Survival

  Post-surgery follow-up of disease and survival occurs every 6 months for 5 years and annually until year 10.

• Median Overall Survival

  Post-surgery follow-up of disease and survival occurs every 6 months for 5 years and annually until year 10.

• Clinical Response Rate (Complete Response)

  Evaluate upon completion of neoadjuvant therapy, up to approximately 18 weeks from study enrollment.

Study Arms (1)

T-DM1 and Pertuzumab

EXPERIMENTAL

T-DM1 3.6 mg per kg of body weight via IV every 3 weeks for 6 doses and Pertuzumab loading dose of 840 mg via IV on Cycle 1 Day 1 followed by maintenance dose of 420 mg via IV every 3 weeks for 6 doses. Excision of tumor/mastectomy of biopsy residual tumor within 42 days of the last cycle of therapy.

Drug: T-DM1; Drug: Pertuzumab; Procedure: Excision of tumor/mastectomy

Interventions

T-DM1 DRUG

Neoadjuvant treatment is for a total of 18 weeks.

Also known as: Kadcyla

T-DM1 and Pertuzumab

Pertuzumab DRUG

Neoadjuvant treatment is for a total of 18 weeks.

Also known as: Perjeta

T-DM1 and Pertuzumab

Excision of tumor/mastectomy PROCEDURE

Definitive breast cancer surgery (excision or mastectomy) marks the end of protocol mandated therapy.

T-DM1 and Pertuzumab

Eligibility Criteria

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

You may qualify if:

• Patients must have HER2-positive Stage II or III histologically confirmed invasive carcinoma of the breast. A minimum tumor size of 2 cm determined by physical exam or imaging is required.
• HER-2 positive, confirmed by central testing (Clarient labs): IHC 3+ and/or FISH positive based on one of the three following criteria:
• Single-probe average HER2 copy number≥6.0 signals/cell OR
• Dual-probe HER2/CEP17 \<2.0 with an average HER2 copy number ≥6.0 signals/cell OR
• Dual-probe HER2/CEP17 ratio ≥2.0
• ER/PR determination is required.
• Bilateral breast cancers are allowed if both cancers are HER2-positive.
• Patients with multifocal or multicentric disease are eligible as long as one area meets eligibility criteria.
• Breast imaging should include the ipsilateral axilla. For subjects with a clinically negative axilla, a sentinel lymph node biopsy will be performed either before or after preoperative therapy at the discretion of the subject's physicians. For subjects with a clinically positive axilla, a needle aspiration, core biopsy or SLN procedure will be performed to determine the presence of metastatic disease in the lymph nodes.
• Men and women (with any menopausal status) ≥ 18 years of age
• ECOG performance status 0 or 1
• Required laboratory values:
• ANC ≥1500/mm3
• Hemoglobin ≥ 9 g/dl
• Platelets ≥100,000/mm3

You may not qualify if:

• Pregnant or nursing women due to the teratogenic potential of the study drugs.
• Active, unresolved infection.
• Receipt of intravenous antibiotics for infection within 7 days prior to enrollment.
• Patients with active liver disease, for example, due to hepatitis B virus, hepatitis C virus, autoimmune hepatic disorder, or sclerosing cholangitis.
• Uncontrolled hypertension (systolic \>180 mm Hg and/or diastolic \>100 mm Hg) or clinically significant (i.e. active) cardiovascular disease: cerebrovascular accident/stroke or myocardial infarction within 6 months prior to first study medication, unstable angina, congestive heart failure (CHF) of New York Heart Association (NYHA) Grade II or higher, or serious cardiac arrhythmia requiring medication.
• Significant symptoms (Grade ≥2) peripheral neuropathy.
• Other concurrent serious diseases that may interfere with planned treatment, including severe pulmonary conditions/illness, uncontrolled infections, uncontrolled diabetes.
• Any prior treatment for the current breast cancer, including chemotherapy, hormonal therapy, radiation or experimental therapy.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Genentech, Inc.: collaborator

Study Sites (4)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Tennessee Oncology/Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

Related Publications (1)

• Li Z, Metzger Filho O, Viale G, dell'Orto P, Russo L, Goyette MA, Kamat A, Yardley DA, Gupta Abramson V, Arteaga CL, Spring LM, Chiotti K, Halsey C, Waks AG, King TA, Lester SC, Bellon JR, Winer EP, Spellman PT, Krop IE, Polyak K. HER2 heterogeneity and treatment response-associated profiles in HER2-positive breast cancer in the NCT02326974 clinical trial. J Clin Invest. 2024 Feb 1;134(7):e176454. doi: 10.1172/JCI176454.

  PMID: 38300710 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Ado-Trastuzumab Emtansine; pertuzumab; Mastectomy

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Maytansine; Macrolides; Lactones; Organic Chemicals; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Trastuzumab; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Surgical Procedures, Operative

Results Point of Contact

• Title: Project Manager
• Organization: Dana-Farber Cancer Institute

ctopm@dfci.harvard.edu

617-632-3500

Study Officials

• Otto Metzger, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 15, 2014
• First Posted: December 30, 2014
• Study Start: January 1, 2015
• Primary Completion: June 1, 2018
• Study Completion (Estimated): January 1, 2028
• Last Updated: April 17, 2026
• Results First Posted: May 11, 2021

Record last verified: 2026-03

Locations

US (4)