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

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)

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.

Study Overview

• Status: Terminated
• Conditions: Breast Cancer; Breast Carcinoma; Cancer of Breast
• Intervention / Treatment: Drug: Palbociclib; Drug: Letrozole; Biological: Trastuzumab; Drug: Goserelin; Procedure: Breast surgery; Procedure: Research tumor biopsy; Procedure: Research bone marrow (OPTIONAL); Procedure: Research blood sample; Genetic: Research blood for germline DNA; Procedure: Blood for detection of circulating tumor cells

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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

Drug: 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.; Other Names: Ibrance; 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.; Other Names: Femara®; Biological: 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.; Other Names: Herceptin®; Drug: 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.; Other Names: Zoladex; Procedure: Breast surgery; Standard of care; Procedure: Research tumor biopsy; Baseline, cycle 1 day 15, and surgery; Procedure: Research bone marrow (OPTIONAL); Baseline and surgery; Procedure: Research blood sample; Baseline, cycle 1 day 15, surgery, and yearly post-surgery for 5 years; Genetic: Research blood for germline DNA; Baseline; Procedure: Blood for detection of circulating tumor cells; Baseline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Pathologic Complete Response (pCR)	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.	Completion of 4 cycles of treatment (approximately 16 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Tolerability of Palbociclib in Combination With Neoadjuvant Letrozole and Trastuzumab (or FDA Approved Biosimilar) as Measured by Number of Participants With Grade 3 & 4 Adverse Events	-The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting.	30 days after completion of neoadjuvant therapy (approximately 21 weeks)
Change in Patient Reported Outcomes as Measured by NCI PRO-CTCAE	Answers ranging from None to Very Severe (none=0 to very severe=4); Not at All to Very Much (not at all=0 to very much=4), Never to Almost Constantly (0=never to almost constantly=4); 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 analyze PRO-CTCAE data longitudinally.; PRO-CTCAE scores for each attribute (frequency, severity and/or interference) will be presented descriptively	Baseline, cycle 2 day 1 (approximately 29 days), and end of cycle 4 (approximately 16 weeks)

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: Pfizer; Rising Tide Foundation
• Investigators: Principal Investigator: Foluso O Ademuyiwa, M.D, MPH, Washington University School of Medicine

Publications and helpful links

Helpful Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2017
• Primary Completion (Actual): August 24, 2020
• Study Completion (Actual): September 23, 2020

Study Registration Dates

• First Submitted: September 14, 2016
• First Submitted That Met QC Criteria: September 14, 2016
• First Posted (Estimate): September 20, 2016

Study Record Updates

• Last Update Posted (Actual): September 29, 2021
• Last Update Submitted That Met QC Criteria: September 8, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Immunological; Protein Kinase Inhibitors; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Trastuzumab; Letrozole; Palbociclib; Goserelin
• Other Study ID Numbers: 201610019

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No