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Breast Cancer FemalePhase 3NCT03969121

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

A Phase 3 study testing Palbociclib and Endocrine therapy in people with Breast Cancer Female and Hormone Receptor Positive Malignant Neoplasm of Breast, run by Kyoto Breast Cancer Research Network at 25 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Palbociclib and Endocrine therapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
141 participants
Where
25 sitesin 5 countries
Study dates
16 Jul 2019to 23 Dec 2021
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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
  • AST and ALT: ≤ 2 × ULN
  • Cardiac function: Normal finding of Electrocardiogram (ECG) QTc ≤ 480 msec (based on the mean value of the triplicate ECGs).
  • Able to give written informed consent form
  • Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures

Who cannot join

  • 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.
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  • 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.
  • Prior hematopoietic stem cell or bone marrow transplantation.
  • Known abnormalities in coagulation such as bleeding diathesis, or treatment with anticoagulants precluding subcutaneous injections of leuprorelin or goserelin.
  • Hepatitis B and/or hepatitis C carriers (Patients with HBsAg+ or HBV-DNA+ who need antiviral treatment during any anti-cancer therapy based on guidelines are excluded even if the patient's hepatic function is normal. Patients with HCVAb+, whose HCV-RNA is positive (+) are excluded.)
  • Known human immunodeficiency virus (HIV) infection
  • Known hypersensitivity to anti-aromatase drugs, tamoxifen or any cell cycle in-hibitor.
  • Patients who are pregnant or lactating. Patients of childbearing potential and/or her partner who are unwilling or unable to use a method of highly effective non-hormonal contraception throughout the study and continue for at least 21 days in patients after the last dose of investigational drug.
  • Other severe acute or chronic medical or psychiatric condition, or laboratory ab-normality that would impart, in the judgment of the investigator, excess risk as-sociated with study participation or study drug administration, or which, in the judgment of the investigator, would make the patient inappropriate for entry into this study
  • Patients who are investigational site staff members or relatives of those site staff OOTR-N016/KBCRN-B-003/HT-PAB Protocol (version 1.2 dated Oct 11, 2018) 24 members or patients who are the sponsor employees directly involved in the con-duct of the trial.
  • Participation in other studies involving investigational drug (s) (Phases 1-4) within 2 weeks before randomization and/or until a visit at 4 weeks (+7 days) after operation.

Trial locations and contacts

25 sites in 5 countries.

25 sites in 5 countries

Japan14 sites

  • Amagasaki General Medical Center

    Amagasaki, Hyōgo, 660-8550

  • Kyushu Cancer Center

    Fukuoka, 811-1395

  • Sagara Hospital

    Kagoshima, 892-0833

  • Kobe City Medical Center General Hospital

    Kobe, 650-0047

  • Kyoto University Hospital

    Kyoto, 606-8507

  • Aichi Cancer Center

    Nagoya, 464-8681

  • Tazuke Kofukai, Medical Research Institute, Kitano Hospital

    Osaka, 530-8480

  • Saitama Cancer Center

    Saitama, 362-0806

  • Toranomon Hospital

    Tokyo, 105-8470

  • Tokyo Metropolitan Komagome Hospital

    Tokyo, 113-8677

  • Cancer Institute Hospital Of JFCR

    Tokyo, 135-8550

  • Kyorin University Hospital

    Tokyo, 181-8611

  • University of Tsukuba Hospital

    Tsukuba, Ibaraki, 305-8576

  • Kanagawa Cancer Center

    Yokohama, 241-8515

Other trials in Japan

South Korea4 sites

  • National Cancer Center, Korea

    Gyeonggi-do

  • Seoul National University Bundang Hospital

    Seongnam

  • Korea Cancer Center Hospital

    Seoul

  • Seoul National University College of Medicine

    Seoul

Other trials in South Korea

Taiwan4 sites

  • Changhua Christian Hospital

    Changhua

  • Kaohsiung Medical University Chung-Ho Memorial Hospital

    Kaohsiung City

  • National Taiwan University Hospital

    Taipei

  • Sun Yat-Sen Cancer Center

    Taipei

Other trials in Taiwan

Australia2 sites

  • Monash Health

    Clayton, 3168

  • Peter MacCallum Cancer Centre

    Melbourne

Other trials in Australia

Hong Kong1 site

  • UNIMED Medical Institute

    Hong Kong

Other trials in Hong Kong

About this study

Official title: A Phase III Randomized, Double-Blind, Neoadjuvant Study of Hormonal Therapy Plus Palbociclib Versus Hormonal Therapy Plus Placebo in Women With Operable, Hormone Sensitive and HER2-Negative Primary Breast Cancer

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.

Being tested
Palbociclib, Endocrine therapy
Keywords
Palbociclib, Breast Cancer, PEPI
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PalbociclibDrug

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

  • Endocrine therapyDrug

    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.

Study groups in NCT03969121
Study groupRoleWhat they receive
Placebo + Endocrine therapyActive comparatorEndocrine therapy for 16 weeks plus placebo
Receives: Drug: Endocrine therapy
Palbociclib + Endocrine therapyActive comparatorEndocrine therapy for 16 weeks plus Palbociclib
Receives: Drug: Palbociclib; Drug: Endocrine therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 4 months

  2. 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.

    Measured: 4 months

Secondary outcomes (5)

  1. Clinical Response Rate

    Observing any reduction in largest tumor diameter on clinical breast examination and ultrasound imaging of breast and axilla after 4 months

    Measured: 4 months

  2. Ki67 change

    Drop in Ki67 index to less than or equal to 2.7%

    Measured: 4 months

  3. pathological response rate

    Evaluating the rate of pathological Complete Response based on assessment of surgical specimen

    Measured: 4 months

  4. Breast conserving rate

    Calculating the rate of breast conserving surgery based on the number of each surgery type

    Measured: 4 months

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

    Type, incidence, severity (as graded by National Cancer Institute - Common Terminology Criteria for Adverse Events [NCI CTCAE] v4.03), seriousness and relationship to study medications of adverse events (AE) and any laboratory abnormalities

    Measured: 4 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 May 2019
  2. Study start16 Jul 2019
  3. Primary completion23 Dec 2021
  4. Study completion23 Dec 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
141 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03969121
Sponsor's protocol ID
OOTR-N016/KBCRN-B-003/HT-PAB
Status last verified
Jun 2021
First submitted
13 May 2019
Last updated
10 Mar 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • 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.

    PubMed 40888443

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Palbociclib and Endocrine therapy in people with Breast Cancer Female and Hormone Receptor Positive Malignant Neoplasm of Breast, run by Kyoto Breast Cancer Research Network at 25 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 25 sites in Japan, South Korea, Taiwan, Australia, Hong Kong. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pre-operative Endocrine Prognostic Index (PEPI Score) (time frame: 4 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03969121, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Mar 2023.

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