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

Breast Cancer Clinical Trial

— PALTAN  

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 Details — Status: Terminated

Administrative data

• NCT number: NCT02907918
• Other study ID #: 201610019
• Status: Terminated
• Phase: Phase 2
• Start date: June 30, 2017
• Est. completion date: September 23, 2020

Study information

• Verified date: September 2021
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 26
• Est. completion date: September 23, 2020
• Est. primary completion date: August 24, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Carcinoma
• Breast Neoplasms
• Cancer of Breast

Intervention

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.
• 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.

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.

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.

Procedure:
• Breast surgery
Standard of care
• Research tumor biopsy
Baseline, cycle 1 day 15, and surgery
• Research bone marrow (OPTIONAL)
Baseline and surgery
• 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

Locations

Country	Name	City	State
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Mayo Clinic	Phoenix	Arizona
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (3)

Lead Sponsor	Collaborator
Washington University School of Medicine	Pfizer, Rising Tide Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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)

External Links

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