Clinical Trials /

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

NCT02907918

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Terminated

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Neoadjuvant Study of Palbociclib in Combination With Letrozole and Trastuzumab in Stage II-III ER+ HER2+ Breast Cancer
  • 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)

Clinical Trial IDs

  • ORG STUDY ID: 201610019
  • NCT ID: NCT02907918

Conditions

  • Breast Cancer
  • Cancer of Breast
  • Breast Carcinoma

Interventions

DrugSynonymsArms
PalbociclibIbrancePalbociclib + letrozole + trastuzumab +/- goserelin
LetrozoleFemara®Palbociclib + letrozole + trastuzumab +/- goserelin
TrastuzumabHerceptin®Palbociclib + letrozole + trastuzumab +/- goserelin
GoserelinZoladexPalbociclib + letrozole + trastuzumab +/- goserelin

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.

Trial Arms

NameTypeDescriptionInterventions
Palbociclib + letrozole + trastuzumab +/- goserelinExperimentalNeoadjuvant 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
  • Palbociclib
  • Letrozole
  • Trastuzumab
  • Goserelin

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Pathologic complete response (pCR) rate
Time Frame:Completion of 4 cycles of treatment (approximately 16 weeks)
Safety Issue:
Description: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

Measure: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)
Safety Issue:
Description:-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.
Measure:Patient reported outcomes as measured by NCI PRO-CTCAE
Time Frame:Completion of treatment (approximately 16 weeks)
Safety Issue:
Description: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

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Terminated
Lead Sponsor:Washington University School of Medicine

Last Updated

October 14, 2020