Pertuzumab and Trastuzumab as Neoadjuvant Treatment in Patients With HER2-Positive Breast Cancer

NCT01937117 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 3 other identifiers: TBCRC 026TBCRC026NA_00080994
• Study Type: interventional
• Target: 88
• Locations: 1 country
• Sites: 10

Brief Summary

This research is being done to determine if early changes on a type of imaging procedure called PET (Positron Emission Tomography) can predict which patients are most likely to respond to the combination of trastuzumab and pertuzumab when given prior to surgery.

Conditions

Breast Cancer

Keywords

Breast cancer; Preoperative treatment; Neoadjuvant treatment

Outcome Measures

Primary Outcomes (1)

• Percent Change in Standardized Uptake Value (SUV) as Measured by SULmax on [18F]Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET)

  SULmax is the maximum SUV corrected for lean body mass. Change in SULmax from baseline to Day 15 on FDG PET in correlation with pathological complete response (pCR) in patients treated with preoperative pertuzumab/trastuzumab. pCR was defined as no viable invasive cancer in breast and axilla by local pathology review. SULmax was measured via spherical volume over the target primary breast cancer tissue.

  Baseline and Day 15

Secondary Outcomes (3)

• Change in ptDNA With Response

  3 years

• Change in PI3K Pathway Activation With Response

  3 years

• Changes in Ki67 With Response

  3 years

Study Arms (1)

Trastuzumab and Pertuzumab

EXPERIMENTAL

Preoperative treatment with trastuzumab (8 mg/kg loading dose, then 6 mg/kg every 3 weeks, IV) and pertuzumab (840 mg as a loading dose, then 420 mg every 3 weeks, IV) every 3 weeks for 4 doses (total 12 weeks or 3 months of treatment) as assessed by Positron Emission Tomography (PET)

Procedure: Positron emission tomography (PET); Drug: Trastuzumab; Drug: Pertuzumab

Interventions

Positron emission tomography (PET) PROCEDURE

PET will be performed at baseline and on day 15

Also known as: FDG PET, PET/CT

Trastuzumab and Pertuzumab

Trastuzumab DRUG

8 mg/kg loading dose, then 6 mg/kg every 3 weeks, IV

Also known as: Herceptin

Trastuzumab and Pertuzumab

Pertuzumab DRUG

840 mg as a loading dose, then 420 mg every 3 weeks, IV

Also known as: Perjeta

Trastuzumab and Pertuzumab

Eligibility Criteria

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

You may qualify if:

• Female and male patients, 18 years old or older
• Histologically proven infiltrating carcinoma of the breast on core needle biopsy that is: estrogen receptor (ER)/progesterone receptor (PR) ≤10% staining by immunohistochemistry (IHC) and HER2 positive - IHC 3+, in situ hybridization (ISH) ≥2.0, or average HER2 copy number ≥6.0 signals per cell or per current American Society of Clinical Oncology - College of American Pathologists (ASCO-CAP) or National Comprehensive Cancer Network (NCCN) guidelines. Note: All histological diagnostic material should be reviewed at enrolling institution as required per local standards.
• Unresected, untreated breast cancer that meets one of the following clinical stages (see Appendix A): T2, T3, or T4a-c lesion, any N, M0. Note: Patients with inflammatory breast cancer (T4d) are not eligible. Bilateral cancers are permitted with approval of the Protocol Chair.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (Appendix B)
• Adequate organ function as follows:
• Absolute neutrophil count (ANC) ≥ 1,500/mm3
• Platelet count ≥ 100,000/mm3
• Hemoglobin ≥ 10 g/dL
• Creatinine ≤ 1.5 times the upper limit of normal with creatinine clearance ≥ 50 mL/min using the Modified Cockcroft-Gault method
• Bilirubin (total) ≤ 1.5 times upper limit normal (with exception of Gilberts syndrome)
• AST(SGOT), ALT(SGPT), and alkaline phosphatase ≤ 2 times the upper limit of normal
• Adequate cardiac function as defined by left ventricular ejection fraction (LVEF) ≥ 50% on echocardiogram or multi-gated acquisition scan (MUGA)
• Able and amenable to baseline and follow-up PET/CT imaging and study-specific biopsy procedures. Note: If there are any imaging concerns that the patient may not be suitable for quantitative PET/CT (e.g., a metallic device directly overlies the breast), discussion with the local and central radiologists is required to confirm eligibility for the trial. Also, it is expected that subjects have all PET/CT imaging done on pre-qualified machines for the study; if baseline imaging done on another machine, please contact the Protocol Chair/designee for guidance prior to confirming eligibility.
• The patient, if of childbearing potential, is willing to use effective, non-hormonal contraception while on treatment and for at least 6 months following the last dose of therapy.
• Patient understands the study regimen, its requirements, risks, and discomforts, and is able and willing to sign an informed consent form.

You may not qualify if:

• Received prior or ongoing local (e.g radiation) or systemic treatment (chemotherapy or endocrine therapy) for the current breast cancer. Patients who received tamoxifen or raloxifene or another agent for prevention of breast cancer may be included as long as the patient has discontinued the treatment at least one month prior to baseline study biopsy.
• Systemic treatment for prior cancer within the last 5 years, with the exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin.
• Women who are pregnant or nursing
• Current use of any investigational agents
• Known hypersensitivity to trastuzumab or pertuzumab
• Any medical condition that in the opinion of the investigator puts the patient at risk of potentially serious complications while on this therapy. Specifically, uncontrolled hypertension (systolic \>150 and/or diastolic \>100), unstable angina, congestive heart failure of any New York Heart Association (NYHA) classification, serious cardiac arrhythmia requiring treatment (exception: atrial fibrillation, paroxysmal supraventricular tachycardia), history of myocardial infarction within 6 months of enrollment.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• Translational Breast Cancer Research Consortium: collaborator
• Genentech, Inc.: collaborator

Study Sites (10)

University of Alabama Comprehensive Cancer Center

Birmingham, Alabama, 35294, United States

Location

Johns Hopkins Kimmel Cancer Center at Sibley Memorial Hospital

Washington D.C., District of Columbia, 20016, United States

Location

Indiana University Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21287-0013, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

Location

Vanderbilt University

Nashville, Tennessee, 37232, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Fred Hutchinson Cancer Research Center - University of Washington

Seattle, Washington, 98109, United States

Location

Related Publications (2)

• Connolly RM, Leal JP, Solnes L, Huang CY, Carpenter A, Gaffney K, Abramson V, Carey LA, Liu MC, Rimawi M, Specht J, Storniolo AM, Valero V, Vaklavas C, Krop IE, Winer EP, Camp M, Miller RS, Wolff AC, Cimino-Mathews A, Park BH, Wahl RL, Stearns V. TBCRC026: Phase II Trial Correlating Standardized Uptake Value With Pathologic Complete Response to Pertuzumab and Trastuzumab in Breast Cancer. J Clin Oncol. 2019 Mar 20;37(9):714-722. doi: 10.1200/JCO.2018.78.7986. Epub 2019 Feb 5.

  PMID: 30721110 RESULT

• Hennessy MA, Cimino-Mathews A, Carter JM, Kachergus JM, Ma Y, Leal JP, Solnes LB, Denbow R, Abramson VG, Carey LA, Rimawi M, Specht J, Storniolo AM, Valero V, Vaklavas C, Winer EP, Krop IE, Wolff AC, Wahl RL, Perez EA, Huang CY, Stearns V, Thompson EA, Connolly RM. Multiplex Spatial Proteomic Analysis of HER2-Positive Breast Tumors Reveals Unique Molecular and Immunologic Features Associated With Treatment Response. JCO Precis Oncol. 2025 Apr;9:e2400546. doi: 10.1200/PO-24-00546. Epub 2025 Apr 3.

  PMID: 40179327 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Magnetic Resonance Spectroscopy; Trastuzumab; pertuzumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Jenna Canzoniero, MD
• Organization: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

jcanzon1@jhmi.edu

410-955-8983

Study Officials

• Roisin Connolly, MBBCh

  Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

  STUDY CHAIR

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: SPONSOR

Study Record Dates

• First Submitted: September 3, 2013
• First Posted: September 9, 2013
• Study Start: January 30, 2014
• Primary Completion: March 20, 2018
• Study Completion (Estimated): June 1, 2026
• Last Updated: July 1, 2025
• Results First Posted: April 12, 2019

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (10)