Clinical Trials /

Neoadjuvant Study of Palbociclib in Combination With Letrozole and Trastuzumab in Stage II-III ER+ HER2+ Breast Cancer

NCT02907918

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title:Neoadjuvant Study of Palbociclib in Combination With Letrozole and Trastuzumab in Stage II-III ER+ HER2+ Breast Cancer
  • Official Title:A Phase II Neoadjuvant Study of Palbociclib in Combination With Letrozole and Trastuzumab as Neoadjuvant Treatment of Stage II-III ER+ HER2+ Breast Cancer (PALTAN)

Clinical Trial IDs

  • ORG STUDY ID: 16-x293
  • NCT ID: NCT02907918

Trial Conditions

  • Breast Cancer
  • Cancer of Breast
  • Breast Carcinoma

Trial Interventions

DrugSynonymsArms
PalbociclibIbrancePalbociclib + letrozole + trastuzumab +/- goserelin
LetrozoleFemara®Palbociclib + letrozole + trastuzumab +/- goserelin
GoserelinZoladexPalbociclib + letrozole + trastuzumab +/- goserelin

Trial Purpose

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.

Detailed Description

Trial Arms

NameTypeDescriptionInterventions
Palbociclib + letrozole + trastuzumab +/- goserelinExperimentalNeoadjuvant palbociclib + letrozole (plus goserelin if premenopausal) + trastuzumab for a total of 16 weeks, consisting of (4) 28-day cycles Definitive surgery within 3-5 weeks after the end of Cycle 4. Letrozole and trastuzumab will continue until the day of surgery. Adjuvant therapy following definitive surgery will be at the discretion of the treating physician 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 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) 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 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
  • Palbociclib
  • Letrozole
    • Goserelin

    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.

    - Tumor size at least 2 cm in one dimension by clinical or radiographic exam (World Health Organization (WHO) criteria).

    - 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 (QTc) < 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 ovarian suppression 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).

    - Receiving medications (within the last 7 days prior to registration) that have the potential of prolonging the QT interval

    - 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.

    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:Both
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Pathologic complete response (pCR) rate
    Time Frame:Completion of 4 cycles of treatment (approximately 16 weeks)
    Safety Issue:No
    Description:A pathologic complete response (pCR) is defined as no histology evidence of invasive tumor cells in the surgical breast specimen and sentinel or axillary lymph nodes.

    Secondary Outcome Measures

    Measure:Safety and tolerability of palbociclib in combination with neoadjuvant letrozole and trastuzumab as measured by frequency of adverse events
    Time Frame:30 days after completion of neoadjuvant therapy (approximately 21 weeks)
    Safety Issue:Yes
    Description:
    Measure:Patient reported outcomes as measured by NCI PRO-CTCAE
    Time Frame:Completion of treatment (approximately 16 weeks)
    Safety Issue:No
    Description:10 item questionnaire with 2 questions per item The first part of the question has answers ranging from None to Very Severe. The second part of the question has answers ranging from Not at All to Very Much PRO-CTCAE responses are scored from 0 to 4, and there are no standardized scoring rules yet established for how to combine attributes into a single score or how best to analyse PRO-CTCAE data longitudinally. PRO-CTCAE scores for each attribute (frequency, severity and/or interference) will be presented descriptively

    Trial Keywords