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

Study Results

Results available

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

26 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-06-30

Study Completion Date

2020-09-23

Brief Summary

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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.

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Detailed Description

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Conditions

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Breast Cancer Cancer of Breast Breast Carcinoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Palbociclib + letrozole + trastuzumab +/- goserelin

* Neoadjuvant palbociclib + letrozole (plus goserelin if premenopausal) + trastuzumab for a total of 16 weeks, consisting of (4) 28-day cycles
* Definitive surgery will be performed preferably within 6 weeks after the end of Cycle 4. Letrozole and trastuzumab will continue until the day of surgery. Letrozole will continue to be taken daily and trastuzumab will be given every 3 weeks per standard of care guidelines. Adjuvant therapy following definitive surgery will be at the discretion of the treating physician

Group Type EXPERIMENTAL

Palbociclib

Intervention Type DRUG

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

Intervention Type DRUG

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.

Trastuzumab

Intervention Type BIOLOGICAL

* 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

Intervention Type DRUG

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.

Breast surgery

Intervention Type PROCEDURE

Standard of care

Research tumor biopsy

Intervention Type PROCEDURE

Baseline, cycle 1 day 15, and surgery

Research bone marrow (OPTIONAL)

Intervention Type PROCEDURE

Baseline and surgery

Research blood sample

Intervention Type PROCEDURE

Baseline, cycle 1 day 15, surgery, and yearly post-surgery for 5 years

Research blood for germline DNA

Intervention Type GENETIC

Baseline

Blood for detection of circulating tumor cells

Intervention Type PROCEDURE

Baseline

Interventions

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Palbociclib

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.

Intervention Type DRUG

Letrozole

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.

Intervention Type DRUG

Trastuzumab

* 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.

Intervention Type BIOLOGICAL

Goserelin

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.

Intervention Type DRUG

Breast surgery

Standard of care

Intervention Type PROCEDURE

Research tumor biopsy

Baseline, cycle 1 day 15, and surgery

Intervention Type PROCEDURE

Research bone marrow (OPTIONAL)

Baseline and surgery

Intervention Type PROCEDURE

Research blood sample

Baseline, cycle 1 day 15, surgery, and yearly post-surgery for 5 years

Intervention Type PROCEDURE

Research blood for germline DNA

Baseline

Intervention Type GENETIC

Blood for detection of circulating tumor cells

Baseline

Intervention Type PROCEDURE

Other Intervention Names

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Ibrance Femara® Herceptin® Zoladex

Eligibility Criteria

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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.

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No