Neoadjuvant Hormonal Therapy Plus Palbociclib in Operable, Hormone Sensitive and HER2-Negative Primary Breast Cancer

NCT03969121 | Completed Phase 3 DMC FDA Drug

• 1 other identifier: OOTR-N016/KBCRN-B-003/HT-PAB
• Study Type: interventional
• Target: 141
• Locations: 5 countries
• Sites: 25

Brief Summary

The study is a randomized, double blind, placebo controlled, Phase 3 clinical trial with the primary objective of demonstrating the efficacy of palbociclib in combination with Endocrine therapy over Endocrine therapy alone measured by PEPI and EndoPredict™ EPclin Score in women with operable HR+, HER2 negative breast cancer . The Clinical Response Rate, drop in Ki67 index ≤ 2.7% and Breast conserving rate will be compared between two arms.

Conditions

Breast Cancer Female; Hormone Receptor Positive Malignant Neoplasm of Breast

Keywords

Palbociclib; Breast Cancer; PEPI

Outcome Measures

Primary Outcomes (2)

• Pre-operative Endocrine Prognostic Index (PEPI Score)

  The PEPI score is derived from four factors assigned a numerical score following neoadjuvant endocrine therapy, ( including Ki67 expression in the surgical specimen, pathologic tumor size, lymph node status, and estrogen receptor (ER) level). The PEPI score is the sum of each component score and shows the risk points for relapse-free survival. PEPI=0 means low risk. PEPI= 1 to 3 means intermediate risk . PEPI more than 4 means high risk.

  4 months

• EndoPredict™ EPclin Score

  EndoPredict is a multigene test used to predict the risk of distant recurrence of early stage, ER positive ,HER-2 Negative invasive breast cancer. EndoPredict Clinical Score (EP clin ) categorizes patinets into low and high risk groups.Combination of the 12-Gene Molecular Score, tumor stage and lymph node status, generating an EPclin Risk Score.The EPclin Risk Score is calculated, according to the model, as: EPclin Risk Score = (0.35 \* tumor size) + (0.64 \* lymph node status) + (0.28 \* 12-Gene Molecular Score) EPclin Risk Scores from 1.0 through 3.3 shows low risk of recurrencein 10 years.EPclin Risk Scores from 3.4 through 6.0 shows high risk of recurrence in 10 years.

  4 months

Secondary Outcomes (5)

• Clinical Response Rate

  4 months

• Ki67 change

  4 months

• pathological response rate

  4 months

• Breast conserving rate

  4 months

• Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment as Assessed by CTCAE v4.03

  4 months

Study Arms (2)

Placebo + Endocrine therapy

ACTIVE COMPARATOR

Endocrine therapy for 16 weeks plus placebo

Drug: Endocrine therapy

Palbociclib + Endocrine therapy

ACTIVE COMPARATOR

Endocrine therapy for 16 weeks plus Palbociclib

Drug: Palbociclib; Drug: Endocrine therapy

Interventions

Palbociclib DRUG

Palbociclib will be administered orally once a day for 21 days every 28-day cycle followed by 7 days off treatment

Palbociclib + Endocrine therapy

Endocrine therapy DRUG

Pre- and peri-menopausal women will be receiving Ovarian Function Suppression (OFS) by either leuprorelin subcutaneous 3.75 mg q28days or goserelin subcutaneous 3.6 mg q28days plus tamoxifen 20 mg QD in 28-day cycles. Post-menopausal women will receive letrozole 2.5 mg QD in 28-day cycles.

Palbociclib + Endocrine therapy; Placebo + Endocrine therapy

Eligibility Criteria

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

You may qualify if:

• Pre/peri- or post-menopausal women 18 years and older (or local legal age, whichever is higher)
• Primary tumor greater than 15 mm in diameter
• Histologically proven invasive breast cancer
• Positive hormone receptor (ER and/or PgR ≥1% in proportion of positive staining score)
• Negative HER-2 receptor (based on 2018 ASCO/CAP Guideline)
• Ki67 index equal to or greater than 14% (Ki67 ≥ 14%) by central assessment using actual or virtual slides
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤ 1
• No previous history of radiotherapy or systemic therapy including chemotherapy and hormone therapy for breast cancer
• Laboratory values must be as follows:
• Absolute neutrophil count: ≥ 1,500/mm3
• Platelets: ≥ 100,000/mm3
• Hemoglobin: ≥ 9 g/dL
• Bilirubin: ≤ 1.5 × upper limits of normal (ULN)
• Serum Creatinine: ≤ 1.5 × ULN
• Alkaline phosphatase: ≤ 2 × ULN

You may not qualify if:

• Male
• Locally advanced breast cancer ( Any T4 or Any N2, N3), or distant metastasis
• Multicentric breast cancer (Note: Multifocal breast cancer,located in one quadrant/are is eligible)
• Prior treatment with chemotherapy, radiotherapy and/or endocrine therapy
• Previous use of SERMs such as raloxifene.
• Prior therapy with any CDK4/6 inhibitor or with everolimus, or any agent whose mechanism of action is to inhibit the PI3K-mTOR pathway.
• Prior history of other malignancy within 5 years of study entry, aside from basal cell carcinoma of the skin or carcinoma-in-situ of the uterine cervix
• Major surgery within 3 weeks of first study treatment
• Patients treated within the last 7 days prior to randomization with:
• Food or drugs that are known strong and moderate CYP3A4 inhibitors (e.g., amprenavir, aprepitant, atazanavir, boceprevir, casopitant, cimetidine, ciprof-loxacin, clarithromycin, conivaptan, cobicistat, crizotinib, cyclosporine, da-runavir, diltiazem, dronedarone, elvitegravir, erythromycin, fluconazole, fosamprenavir, imatinib, indinavir, isavuconazole, istradefylline, itraconazole,ketoconazole, letermovir, lopinavir, mibefradil, miconazole, nefazodone, nelfinavir, nilotinib, posaconazole, ritonavir, saquinavir, schisandra sphenan-thera extract, telaprevir, telithromycin, tofisopam, verapamil, voriconazole, and grapefruit, grapefruit juice or any product containing grapefruit);
• Drugs that are known strong and moderate CYP3A4 inducers (e.g., bosentan, carbamazepine, efavirenz, etravirine, modafinil, phenobarbital, phenytoin, ri-fampin, rifapentin, and St. John's wort);
• Any of the following in the previous 6 months of randomization: myocardial in-farction, severe/unstable angina, ongoing cardiac dysrhythmias of NCI CTCAE version 4.03 grade ≥ 2, atrial fibrillation of any grade, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident in-cluding transient ischemic attack, or symptomatic pulmonary embolism
• Family or personal history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation, or Torsade de Pointes (TdP).
• Uncontrolled electrolyte disorders (eg, hypocalcemia, hypokalemia, hypomag-nesemia) that can compound the effects of a QTc-prolonging drug.
• Active inflammatory bowel disease or chronic diarrhea. Short bowel syndrome. Upper gastrointestinal surgery including gastric resection.

Sponsors & Collaborators

• Kyoto Breast Cancer Research Network: lead
• Pfizer: collaborator

Study Sites (25)

Monash Health

Clayton, 3168, Australia

Location

Peter MacCallum Cancer Centre

Melbourne, Australia

Location

UNIMED Medical Institute

Hong Kong, Hong Kong

Location

Amagasaki General Medical Center

Amagasaki, Hyōgo, 660-8550, Japan

Location

University of Tsukuba Hospital

Tsukuba, Ibaraki, 305-8576, Japan

Location

Kyushu Cancer Center

Fukuoka, 811-1395, Japan

Location

Sagara Hospital

Kagoshima, 892-0833, Japan

Location

Kobe City Medical Center General Hospital

Kobe, 650-0047, Japan

Location

Kyoto University Hospital

Kyoto, 606-8507, Japan

Location

Aichi Cancer Center

Nagoya, 464-8681, Japan

Location

Tazuke Kofukai, Medical Research Institute, Kitano Hospital

Osaka, 530-8480, Japan

Location

Saitama Cancer Center

Saitama, 362-0806, Japan

Location

Toranomon Hospital

Tokyo, 105-8470, Japan

Location

Tokyo Metropolitan Komagome Hospital

Tokyo, 113-8677, Japan

Location

Cancer Institute Hospital Of JFCR

Tokyo, 135-8550, Japan

Location

Kyorin University Hospital

Tokyo, 181-8611, Japan

Location

Kanagawa Cancer Center

Yokohama, 241-8515, Japan

Location

National Cancer Center, Korea

Gyeonggi-do, South Korea

Location

Seoul National University Bundang Hospital

Seongnam, South Korea

Location

Korea Cancer Center Hospital

Seoul, South Korea

Location

Seoul National University College of Medicine

Seoul, South Korea

Location

Changhua Christian Hospital

Changhua, Taiwan

Location

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, Taiwan

Location

National Taiwan University Hospital

Taipei, Taiwan

Location

Sun Yat-Sen Cancer Center

Taipei, Taiwan

Location

Related Publications (1)

• Ueno T, Chow LWC, Han W, Huang CS, Mann GB, Morita S, Haga H, Fakhrejahani E, Kobayashi T, Bando H, Inoue K, Tokiwa M, Suwa H, Aruga T, Minamiguchi S, Yamada Y, Tanabe Y, Takada M, Yamashita T, Iwata H, Chung CF, Takahara S, Tokunaga E, Imoto S, Lee ES, Sagara Y, Kim JH, DeBoer RH, Kim HA, Lai HW, Hou MF, White M, Umeyama Y, Toi M. Neoadjuvant palbociclib in women with operable, hormone receptor-positive breast cancer. Endocr Relat Cancer. 2025 Sep 11;32(9):e240353. doi: 10.1530/ERC-24-0353. Print 2025 Sep 1.

  PMID: 40888443 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

palbociclib

Condition Hierarchy (Ancestors)

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

Study Officials

• Masakazu Toi, MD,PhD

  Kyoto University, Professor of Breast Surgery Department

  PRINCIPAL INVESTIGATOR

• Louis WC Chow, MD,PhD

  Organisation for Oncology and Translational Research (OOTR)

  PRINCIPAL INVESTIGATOR

• Takayuki Ueno, MD,PhD

  Cancer Institute Hospital of JFCR, Department Director, Breast Surgical Oncology Department

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 13, 2019
• First Posted: May 31, 2019
• Study Start: July 16, 2019
• Primary Completion: December 23, 2021
• Study Completion: December 23, 2021
• Last Updated: March 10, 2023

Record last verified: 2021-06

Locations

TW (4); HK (1); AU (2); JP (14); KR (4)