Pertuzumab and Trastuzumab as Neoadjuvant Treatment in Patients With HER2-Positive Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Positron emission tomography (PET); Trastuzumab; Pertuzumab
Intervention description: PET will be performed at baseline and on day 15; 8 mg/kg loading dose, then 6 mg/kg every 3 weeks, IV; 840 mg as a loading dose, then 420 mg every 3 weeks, IV
Intervention MeSH terms: Trastuzumab; Pertuzumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 88.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Breast cancer; Preoperative treatment; Neoadjuvant treatment

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.
    

Eligibility 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: 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:

          -  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.