Neoadjuvant Study of Palbociclib in Combination With Letrozole and Trastuzumab in Stage II-III ER+ HER2+ Breast Cancer
Condition: Breast Cancer; Cancer of Breast; Breast Carcinoma
MeSH terms: Breast Neoplasms
Intervention: Palbociclib; Letrozole; Trastuzumab; Goserelin; Breast surgery; Research tumor biopsy; Research bone marrow (OPTIONAL); Research blood sample; Research blood for germline DNA; Blood for detection of circulating tumor cells
Intervention description: Palbociclib is an oral drug given at a dose of 125 mg daily on Days 1-21 of each 28-day cycle for a total of 4 cycles.; Letrozole is an oral drug given at a dose of 2.5 mg orally once a day. It will be taken continuously (Days 1-28 of each cycle) until the day of definitive surgery.; Or FDA approved biosimilar
Trastuzumab will be administered on a weekly basis for 16 weeks (on Days 1, 8, 15, and 22 of each 28-day cycle for a total of 4 cycles). The first dose of trastuzumab on Cycle 1 Day 1 will be a loading dose of 4 mg/kg IVPB over 90 minutes. Subsequent doses of trastuzumab will be 2 mg/kg IVPB over 30 minutes. Weekly trastuzumab will continue after the completion of Cycle 4 of palbociclib until surgery.; Goserelin is given subcutaneously at a dose of 3.6 mg on Day 1 of each cycle. Goserelin will be continued (once every 28-days) after the completion of Cycle 4 of palbociclib if required.; Standard of care; Baseline, cycle 1 day 15, and surgery; Baseline and surgery; Baseline, cycle 1 day 15, surgery, and yearly post-surgery for 5 years; Baseline; Baseline
Intervention MeSH terms: Trastuzumab; Letrozole; Palbociclib; Goserelin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 26.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The investigators propose to influence estrogen receptor (ER) signaling by combining
      endocrine therapy with CDK4/6 inhibition along with trastuzumab in ER+/ human epidermal
      growth factor receptor 2 (HER2)+ early stage breast cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Newly diagnosed clinical stage II or III ER+/HER2+ breast cancer with complete
             surgical excision of the breast cancer after neoadjuvant therapy as the treatment
             goal, staging criteria is to be based on AJCC 7.

          -  Tumor size at least 2 cm in one dimension by clinical or radiographic exam (World
             Health Organization (WHO) criteria). Patients with histologically confirmed palpable
             lymph nodes may be enrolled regardless of breast tumor size. A palpable mass is not
             required as long as the mass is at least 2 cm in one dimension by radiographic exam.

          -  At least 18 years of age.

          -  Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1

          -  Normal bone marrow and organ function as defined below:

               -  Leukocytes ≥ 3,000/mcL

               -  Absolute neutrophil count ≥ 1,500/mcl

               -  Platelets ≥ 100,000/mcl

               -  Total bilirubin ≤ institutional upper limit of normal (IULN)

               -  AST(SGOT)/ALT(SGPT) ≤ 2.5 x IULN

          -  Creatinine ≤ IULN OR creatinine clearance ≥ 60 mL/min/1.73 m^2 for patients with
             creatinine levels above institutional normal

          -  Left ventricular ejection fraction (LVEF) ≥ 50% by transthoracic echocardiogram or
             multigated acquisition scan (MUGA)

          -  Baseline corrected QT interval (QTcF) < 480 ms

          -  Women of childbearing potential must agree to undergo pregnancy testing within 14 days
             of study entry and agree to use adequate contraception (barrier method of birth
             control, abstinence, not hormonal) prior to study entry and for the duration of study
             participation as well as chemical LHRH Agonist with goserelin. Should a woman become
             pregnant or suspect she is pregnant while participating in this study, she must inform
             her treating physician immediately.

          -  Ability to understand and willingness to sign an IRB approved written informed consent
             document (or that of legally authorized representative, if applicable).

        Exclusion Criteria:

          -  Prior systemic therapy for indexed breast cancer.

          -  Indeterminate or negative HER2 status.

          -  Inflammatory breast cancer.

          -  A history of other malignancy ≤ 5 years from diagnosis of indexed BC with the
             exception of basal cell or squamous cell carcinoma of the skin treated with local
             resection only or carcinoma in situ of the cervix.

          -  Currently receiving any other investigational agents or received any within the past
             28 days.

          -  Know to be HIV positive.

          -  Known hepatitis B or C infection.

          -  A history of allergic reactions attributed to compounds of similar chemical or
             biologic composition to palbociclib, letrozole, trastuzumab, any other aromatase
             inhibitor, any other monoclonal antibody, or other agents used in the study.

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac
             arrhythmia.

          -  Current use or anticipated need for food or drugs that are known strong CYP3A4
             inhibitors (i.e., grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole,
             posaconazole, erythromycin, clarithromycin, telithromycin, indinavir, saquinavir,
             ritonavir, nelfinavir, lopinavir, atazanavir, amprenavir, fosamprenavir, nefazodone,
             diltiazem, and delavirdine) or inducers (i.e. dexamethasone, glucocorticoids,
             progesterone, rifampin, phenobarbital, St. John's wort).

          -  Any condition that impairs the ability to swallow or absorb oral medication (e.g.,
             gastrointestinal tract disease resulting in an inability to take oral medication or a
             requirement for IV alimentation, prior surgical procedures affective absorption).

          -  Pregnant and/or breastfeeding. Women of childbearing potential must have a negative
             pregnancy test within 14 days of study entry.