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

NCT02907918 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 201610019
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 3

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.

Conditions

Breast Cancer; Cancer of Breast; Breast Carcinoma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• 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

  30 days after completion of neoadjuvant therapy (approximately 21 weeks)

• Change in Patient Reported Outcomes as Measured by NCI PRO-CTCAE

  Baseline, cycle 2 day 1 (approximately 29 days), and end of cycle 4 (approximately 16 weeks)

Study Arms (1)

Palbociclib + letrozole + trastuzumab +/- goserelin

EXPERIMENTAL

* 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; 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

Interventions

Palbociclib 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.

Also known as: Ibrance

Palbociclib + letrozole + trastuzumab +/- goserelin

Letrozole 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.

Also known as: Femara®

Palbociclib + letrozole + trastuzumab +/- goserelin

Trastuzumab 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.

Also known as: Herceptin®

Palbociclib + letrozole + trastuzumab +/- goserelin

Goserelin 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.

Also known as: Zoladex

Palbociclib + letrozole + trastuzumab +/- goserelin

Breast surgery PROCEDURE

Standard of care

Palbociclib + letrozole + trastuzumab +/- goserelin

Research tumor biopsy PROCEDURE

Baseline, cycle 1 day 15, and surgery

Palbociclib + letrozole + trastuzumab +/- goserelin

Research bone marrow (OPTIONAL) PROCEDURE

Baseline and surgery

Palbociclib + letrozole + trastuzumab +/- goserelin

Research blood sample PROCEDURE

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

Palbociclib + letrozole + trastuzumab +/- goserelin

Research blood for germline DNA GENETIC

Baseline

Palbociclib + letrozole + trastuzumab +/- goserelin

Blood for detection of circulating tumor cells PROCEDURE

Baseline

Palbociclib + letrozole + trastuzumab +/- goserelin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Pfizer: collaborator
• Rising Tide Foundation: collaborator

Study Sites (3)

Mayo Clinic

Phoenix, Arizona, 85054, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Related Publications (1)

• Ademuyiwa FO, Northfelt DW, O'Connor T, Levine E, Luo J, Tao Y, Hoog J, Laury ML, Summa T, Hammerschmidt T, Guo Z, Frith A, Weilbaecher K, Opyrchal M, Aft R, Clifton K, Suresh R, Bagegni N, Hagemann IS, Iglesia MD, Ma CX. A phase II study of palbociclib plus letrozole plus trastuzumab as neoadjuvant treatment for clinical stages II and III ER+ HER2+ breast cancer (PALTAN). NPJ Breast Cancer. 2023 Jan 6;9(1):1. doi: 10.1038/s41523-022-00504-z.

  PMID: 36609389 DERIVED

Related Links

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

MeSH Terms

Conditions

Breast Neoplasms

Interventions

palbociclib; Letrozole; Trastuzumab; Goserelin; Mastectomy, Segmental; Blood Specimen Collection

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Oligopeptides; Nerve Tissue Proteins; Mastectomy; Surgical Procedures, Operative; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Investigative Techniques

Results Point of Contact

• Title: Foluso O. Ademuyiwa, M.D., MPH
• Organization: Washington University School of Medicine

bisiademuyiwa@wustl.edu

314-454-8313

Study Officials

• Foluso O Ademuyiwa, M.D, MPH

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 14, 2016
• First Posted: September 20, 2016
• Study Start: June 30, 2017
• Primary Completion: August 24, 2020
• Study Completion: September 23, 2020
• Last Updated: September 29, 2021
• Results First Posted: September 5, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)