CClinicalTrials.gg
Sign In
Active, not recruitingNCT01937117Updated Aug 13, 2026Results posted

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

A Phase 2 interventional study of Positron emission tomography (PET) and Trastuzumab in Breast Cancer, sponsored by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins. Active, not recruiting at 10 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-08-13.

Sponsored by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
88
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study 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 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.

02

Conditions studied

  • Breast Cancer

Browse trials for

Keywords

  • Breast cancer
  • Preoperative treatment
  • Neoadjuvant treatment
03

In context

Breast Neoplasms

12,544 studies on the registry are indexed under Breast Neoplasms; 2,892 are open to participants now.

This study's enrollment of 88 is above the median of 72 across 9,303 interventional studies indexed under Breast Neoplasms.

Browse Breast Neoplasms studies →

Lead sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins is the lead sponsor of 572 studies on the registry; 73 are open to participants now.

Of its 111 completed or terminated interventional studies of FDA-regulated products, 67 (60%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • 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:

    1. Absolute neutrophil count (ANC) ≥ 1,500/mm3
    2. Platelet count ≥ 100,000/mm3
    3. Hemoglobin ≥ 10 g/dL
    4. Creatinine ≤ 1.5 times the upper limit of normal with creatinine clearance ≥ 50 mL/min using the Modified Cockcroft-Gault method
    5. Bilirubin (total) ≤ 1.5 times upper limit normal (with exception of Gilberts syndrome)
    6. 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.

Exclusion criteria

Exclusion Criteria:

  • 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.
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
88 participants (actual)

Study arms

  • Experimental
    Trastuzumab and Pertuzumab

    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

  • ProcedurePositron emission tomography (PET)

    PET will be performed at baseline and on day 15

    Also known as: FDG PET, PET/CT

  • DrugTrastuzumab

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

    Also known as: Herceptin

  • DrugPertuzumab

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

    Also known as: Perjeta

06

What researchers measure

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.

    Time frame: Baseline and Day 15

Secondary outcomes

  1. 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

    Time frame: 3 years

  2. 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

    Time frame: 3 years

  3. Changes in Ki67 With Response

    To correlate baseline and change (day 15) in Ki67 with pCR

    Time frame: 3 years

07

Results

Posted Apr 12, 2019

Participant flow

Participant flow — Overall Study
MilestoneTrastuzumab and Pertuzumab
Started88
Completed75
Not completed13
Withdrew: Disease progression7
Withdrew: Physician decision4
Withdrew: Adverse event2

Outcome measures

PrimaryPercent 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.

Time frame:
Baseline and Day 15
Reported as:
Mean · percent reduction in SULmax
Percent Change in Standardized Uptake Value (SUV) as Measured by SULmax on [18F]Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET)
percent reduction in SULmaxTrastuzumab and Pertuzumab
pCR61.9 ± 22.3
no pCR34.3 ± 31.9
SecondaryChange 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

Time frame:
3 years

Results for this outcome have not been posted.

SecondaryChange 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

Time frame:
3 years

Results for this outcome have not been posted.

SecondaryChanges in Ki67 With Response

To correlate baseline and change (day 15) in Ki67 with pCR

Time frame:
3 years

Results for this outcome have not been posted.

Adverse events

Collected over Up to 16 weeks. Non-serious events are listed at a 4.4% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Trastuzumab and Pertuzumab0/88 (0%)2/88 (2.3%)88/88 (100%)
Most frequent serious events
Most frequent serious events
EventTrastuzumab and Pertuzumab
SepsisInjury, poisoning and procedural complications1/88
EnterocolitisGastrointestinal disorders1/88
Most frequent other events
Most frequent other events
EventTrastuzumab and Pertuzumab
DiarrheaGastrointestinal disorders80/88
FatigueGeneral disorders30/88
NauseaGastrointestinal disorders24/88
Rash (NOS)Skin and subcutaneous tissue disorders17/88
HeadacheNervous system disorders13/88
MucositisGastrointestinal disorders12/88
ChillsGeneral disorders10/88
DysgeusiaNervous system disorders6/88
DyspepsiaGastrointestinal disorders5/88
Dry skinSkin and subcutaneous tissue disorders5/88

Baseline characteristics

Age, Continuous
Age, Continuous(years)Trastuzumab and Pertuzumab
Median58 ± 12.6
Sex: Female, Male
Sex: Female, Male(Participants)Trastuzumab and Pertuzumab
Female88
Male0
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Trastuzumab and Pertuzumab
Hispanic or Latino5
Not Hispanic or Latino79
Unknown or Not Reported4
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)Trastuzumab and Pertuzumab
White75
Black or African American7
Other6
Region of Enrollment
Region of Enrollment(Participants)Trastuzumab and Pertuzumab
United States88
Eastern Cooperative Oncology Group (ECOG) Performance Status
Eastern Cooperative Oncology Group (ECOG) Performance Status(Participants)Trastuzumab and Pertuzumab
076
112
Baseline clinical tumor size
Baseline clinical tumor size(cm)Trastuzumab and Pertuzumab
Median3.7 ± 2
Clinical tumor T staging
Clinical tumor T staging(Participants)Trastuzumab and Pertuzumab
T10
T266
T319
T43

6 further baseline measures are reported on the registry.

08

Study locations

10 sites
  • University of Alabama Comprehensive Cancer Center
    Birmingham, Alabama 35294, United States
  • Johns Hopkins Kimmel Cancer Center at Sibley Memorial Hospital
    Washington D.C., District of Columbia 20016, United States
  • Indiana University Simon Cancer Center
    Indianapolis, Indiana 46202, United States
  • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
    Baltimore, Maryland 21287-0013, United States
  • Mayo Clinic
    Rochester, Minnesota 55905, United States
  • Lineberger Comprehensive Cancer Center
    Chapel Hill, North Carolina 27599, United States
  • Vanderbilt University
    Nashville, Tennessee 37232, United States
  • Baylor College of Medicine
    Houston, Texas 77030, United States
  • The University of Texas MD Anderson Cancer Center
    Houston, Texas 77030, United States
  • Fred Hutchinson Cancer Research Center - University of Washington
    Seattle, Washington 98109, United States
09

References and documents

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 30721110 ↗
  • 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. PubMed 40179327 ↗

Study documents

  • Protocol and statistical analysis plan · Jul 30, 2015

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No — There is no plan to share individual patient data.

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Aug 13, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT01937117
Lead sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators
Translational Breast Cancer Research Consortium, Genentech, Inc.
Responsible party
Sponsor
First posted
Sep 9, 2013
Start date
Jan 30, 2014
Primary completion
Mar 20, 2018
Completion
Jun 2027 (estimated)
Results posted
Apr 12, 2019
Last update
Aug 13, 2026

Study contacts

Roisin Connolly, MBBCh
study chair · Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is active, not recruiting, as verified in Jul 2026. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Breast Neoplasms→

Other studies from this sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Start the discussion