Breast CancerPhase 2NCT01937117
Pertuzumab and Trastuzumab as Neoadjuvant Treatment in Patients With HER2-Positive Breast Cancer
A Phase 2 study testing Positron emission tomography (PET), Trastuzumab and Pertuzumab in people with Breast Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 10 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Positron emission tomography (PET), Trastuzumab and Pertuzumab
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 88 participants
- Where
- 10 sitesUnited States
- Study dates
- 30 Jan 2014to Dec 2027
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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.
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United States10 sites
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, 21287-0013
University of Alabama Comprehensive Cancer Center
Birmingham, Alabama, 35294
Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599
Baylor College of Medicine
Houston, Texas, 77030
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Indiana University Simon Cancer Center
Indianapolis, Indiana, 46202
Vanderbilt University
Nashville, Tennessee, 37232
Mayo Clinic
Rochester, Minnesota, 55905
Fred Hutchinson Cancer Research Center - University of Washington
Seattle, Washington, 98109
Johns Hopkins Kimmel Cancer Center at Sibley Memorial Hospital
Washington D.C., District of Columbia, 20016
About this study
Official title: A Phase 2 Clinical Trial Assessing the Correlation of Early Changes in Standardized Uptake Value (SUV) on Positron Emission Tomography (PET) With Pathological Complete Response (pCR) to Pertuzumab and Trastuzumab in Patients With Primary Operable HER2-Positive Breast Cancer
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.
Read the detailed description
This study will evaluate for the first time the correlation between early changes in SUV and pCR in men and women with ER-negative, human epidermal growth factor receptor 2 (HER2)-positive breast cancer receiving trastuzumab and pertuzumab (PT) pre-operatively. This has not previously been evaluated in patients receiving anti HER2 therapy alone and as such is novel and potentially practice changing. The results from this phase 2 biomarker study will be used to plan a randomized study using a predefined cut point for SUV decline such that the investigators can further attempt to identify a group of individuals with HER2-positive early breast cancer who do not require cytotoxic chemotherapy in addition to anti-HER2 agents. This non-invasive biomarker approach will be of great interest to breast cancer oncologists and patients by facilitating a personalized approach to managing patients with HER2-positive disease that will undoubtedly spare toxicity and reduce the costs associated with anti-cancer strategies, without compromising efficacy.
- Conditions
- Breast Cancer
- Being tested
- Positron emission tomography (PET), Trastuzumab, Pertuzumab
- Keywords
- Breast cancer, Preoperative treatment, Neoadjuvant treatment
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Positron emission tomography (PET)Procedure or surgery
Also called FDG PET, PET/CT
PET will be performed at baseline and on day 15
TrastuzumabDrug
Also called Herceptin
8 mg/kg loading dose, then 6 mg/kg every 3 weeks, IV
PertuzumabDrug
Also called Perjeta
840 mg as a loading dose, then 420 mg every 3 weeks, IV
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: Procedure: Positron emission tomography (PET); Drug: Trastuzumab; Drug: Pertuzumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline and Day 15
Secondary outcomes (3)
Change in ptDNA With Response
To correlate PIK3CA mutation status and other genomic alterations (mutations/somatic rearrangements) qualitatively and quantitatively in plasma tumor DNA (ptDNA) with pCR
Measured: 3 years
Change in PI3K Pathway Activation With Response
To correlate PI3K pathway activation (e.g. PTEN low and/or PIK3CA mutation, human epidermal growth factor receptor (HER) 1-4 expression and/or phosphorylation) in tumor samples and pCR
Measured: 3 years
Changes in Ki67 With Response
To correlate baseline and change (day 15) in Ki67 with pCR
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Sep 2013 (estimated)
- Study start30 Jan 2014
- Primary completion20 Mar 2018
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 88 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
- Sponsor type
- University, hospital or other
- Collaborators
- Translational Breast Cancer Research Consortium, Genentech, Inc.
- Responsible party
- Sponsor
- Investigators
- Roisin Connolly, MBBCh, Study chair, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01937117
- Sponsor's protocol ID
- TBCRC 026
- Other IDs
- TBCRC026, NA_00080994
- Status last verified
- Oct 2026
- First submitted
- 3 Sep 2013
- Last updated
- 20 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: There is no plan to share individual patient data.
Publications
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.
PubMed 30721110Hennessy 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.
PubMed 40179327