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

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ClinicalTrials.gov Identifier: NCT01937117
Recruitment Status : Completed
First Posted : September 9, 2013
Last Update Posted : August 14, 2018
Sponsor:
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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.

Condition or disease Intervention/treatment Phase
Breast Cancer Procedure: Positron emission tomography (PET) Drug: Trastuzumab Drug: Pertuzumab Phase 2

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, HER2-positive breast cancer receiving trastuzumab and pertuzumab (PT) pre-operatively. This has not previously been evaluated in patients receiving antiHER2 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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 88 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : January 2014
Actual Primary Completion Date : March 20, 2018
Actual Study Completion Date : April 15, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: Trastuzumab and Pertuzumab
Response to 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)
PET will be performed at baseline and on day 15
Other Name: FDG PET, PET/CT

Drug: Trastuzumab
8 mg/kg loading dose, then 6 mg/kg every 3 weeks, IV
Other Name: Herceptin

Drug: Pertuzumab
840 mg as a loading dose, then 420 mg every 3 weeks, IV
Other Name: Perjeta




Primary Outcome Measures :
  1. Change in SUV on FDG PET [ Time Frame: 3 months ]
    To correlate baseline and change (day 15) in SUV on FDG PET with pathological complete response (pCR) in patients treated with preoperative pertuzumab/trastuzumab


Secondary Outcome Measures :
  1. Change in ptDNA with response [ Time Frame: 3 months ]
    To correlate PIK3CA mutation status and other genomic alterations (mutations/somatic rearrangements) qualitatively and quantitatively in plasma tumor DNA (ptDNA) with pCR

  2. Change in PI3K pathway activation with response [ Time Frame: 3 months ]
    To correlate PI3K pathway activation (e.g. PTEN low and/or PIK3CA mutation, HER 1-4 expression and/or phosphorylation) in tumor samples and pCR

  3. Changes in Ki67 with response [ Time Frame: 3 months ]
    To correlate baseline and change (day 15) in Ki67 with pCR



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Female and male patients, 18 years old or older
  • Histologically proven infiltrating carcinoma of the breast on core needle biopsy that is: ER/PR ≤10% staining by IHC and HER2 positive - IHC 3+, ISH ≥2.0, or average HER2 copy number ≥6.0 signals per cell or per current ASCO-CAP (American Society of Clinical Oncology - College of American Pathologists) or NCCN (National Comprehensive Cancer Network) 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.
  • 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 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:

  • 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.

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To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01937117


Locations
United States, Alabama
University of Alabama Comprehensive Cancer Center
Birmingham, Alabama, United States, 35294
United States, District of Columbia
Johns Hopkins Kimmel Cancer Center at Sibley Memorial Hospital
Washington, District of Columbia, United States, 20016
United States, Indiana
Indiana University Simon Cancer Center
Indianapolis, Indiana, United States, 46202
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21287-0013
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, North Carolina
Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, United States, 27599
United States, Tennessee
Vanderbilt University
Nashville, Tennessee, United States, 37232
United States, Texas
Baylor College of Medicine
Houston, Texas, United States, 77030
The University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Washington
Fred Hutchinson Cancer Research Center - University of Washington
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Investigators
Study Chair: Roisin Connolly, MBBCh Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
ClinicalTrials.gov Identifier: NCT01937117     History of Changes
Other Study ID Numbers: TBCRC 026
TBCRC026 ( Other Identifier: Translational Breast Cancer Research Consortium (TBCRC) )
NA_00080994 ( Other Identifier: JHMIRB )
First Posted: September 9, 2013    Key Record Dates
Last Update Posted: August 14, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: There is no plan to share individual patient data.

Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins:
Breast cancer
Preoperative treatment
Neoadjuvant treatment

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Pertuzumab
Trastuzumab
Antineoplastic Agents