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Trial record 9 of 20 for:    breast cancer AND premenopausal | Open Studies | United States

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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified April 2017 by Washington University School of Medicine
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT02907918
First received: September 14, 2016
Last updated: April 11, 2017
Last verified: April 2017
  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.

Condition Intervention 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
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
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)

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • 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:
  • 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) ]
    -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.

  • 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


Estimated Enrollment: 48
Anticipated Study Start Date: May 31, 2017
Estimated Study Completion Date: October 31, 2024
Estimated Primary Completion Date: October 31, 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 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
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
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

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
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.
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02907918

Contacts
Contact: Foluso O Ademuyiwa, M.D., MPH (314) 454-8313 bisiademuyiwa@wustl.edu

Locations
United States, Kentucky
St. Elizabeth Physicians Not yet recruiting
Edgewood, Kentucky, United States, 41017
Contact: J. Michael Guenther, M.D.    859-344-1600      
United States, Missouri
Washington University School of Medicine Not yet recruiting
St. Louis, Missouri, United States, 63110
Contact: Foluso O Ademuyiwa, M.D., MPH    314-454-8313    bisiademuyiwa@wustl.edu   
Principal Investigator: Foluso O Ademuyiwa, M.D., MPH         
Sub-Investigator: Cynthia X Ma, M.D, Ph.D.         
Sub-Investigator: Rebecca L Aft, M.D., Ph.D.         
Sub-Investigator: Ron Bose, M.D.         
Sub-Investigator: Matthew Cherian, M.D.         
Sub-Investigator: Amy Cyr, M.D.         
Sub-Investigator: Timothy Eberlein, M.D.         
Sub-Investigator: Ashley Frith, M.D.         
Sub-Investigator: Will Gillanders, M.D.         
Sub-Investigator: Leonel Hernandez-Aya, M.D.         
Sub-Investigator: Julie Margenthaler, M.D.         
Sub-Investigator: Peter Oppelt, M.D.         
Sub-Investigator: Haesong Park, M.D.         
Sub-Investigator: Caron Rigden, M.D.         
Sub-Investigator: Souzan Sanati, M.D.         
Sub-Investigator: Rama Suresh, M.D.         
Sub-Investigator: Lindsey Peterson, M.D.         
Sub-Investigator: R. Reid Townsend, M.D., Ph.D.         
United States, Texas
Laredo Breast Care Not yet recruiting
Laredo, Texas, United States, 78041
Contact: Gary Unzeitig, M.D.         
Sponsors and Collaborators
Washington University School of Medicine
Pfizer
Investigators
Principal Investigator: Foluso O Ademuyiwa, M.D, MPH Washington University School of Medicine
  More Information

Additional Information:
Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT02907918     History of Changes
Other Study ID Numbers: 201610019
Study First Received: September 14, 2016
Last Updated: April 11, 2017
Individual Participant Data  
Plan to Share IPD: No

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

ClinicalTrials.gov processed this record on May 25, 2017