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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02907918
Recruitment Status : Terminated (Futility)
First Posted : September 20, 2016
Last Update Posted : October 14, 2020
Sponsor:
Collaborators:
Pfizer
Rising Tide Foundation
Information provided by (Responsible Party):
Washington University School of Medicine

Brief 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.

Condition or disease Intervention/treatment Phase
Breast Cancer Cancer of Breast Breast Carcinoma 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 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 26 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : June 30, 2017
Actual Primary Completion Date : August 24, 2020
Actual Study Completion Date : September 23, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

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 Name: 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 Name: 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 Name: 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 Name: 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




Primary Outcome Measures :
  1. Pathologic complete response (pCR) rate [ Time Frame: Completion of 4 cycles of treatment (approximately 16 weeks) ]
    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 :
  1. Safety and tolerability of palbociclib in combination with neoadjuvant letrozole and trastuzumab (or FDA approved biosimilar) as measured by frequency of adverse events [ Time Frame: 30 days after completion of neoadjuvant therapy (approximately 21 weeks) ]
    -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.

  2. Patient reported outcomes as measured by NCI PRO-CTCAE [ Time Frame: Completion of treatment (approximately 16 weeks) ]
    • 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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02907918


Locations
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United States, Arizona
Mayo Clinic
Phoenix, Arizona, United States, 85054
United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
Sponsors and Collaborators
Washington University School of Medicine
Pfizer
Rising Tide Foundation
Investigators
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Principal Investigator: Foluso O Ademuyiwa, M.D, MPH Washington University School of Medicine
Additional Information:
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Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT02907918    
Other Study ID Numbers: 201610019
First Posted: September 20, 2016    Key Record Dates
Last Update Posted: October 14, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Trastuzumab
Letrozole
Palbociclib
Goserelin
Antineoplastic Agents, Immunological
Antineoplastic Agents
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Protein Kinase Inhibitors
Antineoplastic Agents, Hormonal