- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03969121
Neoadjuvant Hormonal Therapy Plus Palbociclib in Operable, Hormone Sensitive and HER2-Negative Primary Breast Cancer
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
Study Overview
Status
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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Clayton, Australia, 3168
- Monash Health
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Melbourne, Australia
- Peter MacCallum Cancer Centre
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Hong Kong, Hong Kong
- UNIMED Medical Institute
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Fukuoka, Japan, 811-1395
- Kyushu Cancer Center
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Kagoshima, Japan, 892-0833
- Sagara Hospital
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Kobe, Japan, 650-0047
- Kobe City Medical Center General Hospital
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Kyoto, Japan, 606-8507
- Kyoto University Hospital
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Nagoya, Japan, 464-8681
- Aichi Cancer Center
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Osaka, Japan, 530-8480
- Tazuke Kofukai, Medical Research Institute, Kitano Hospital
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Saitama, Japan, 362-0806
- Saitama Cancer Center
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Tokyo, Japan, 105-8470
- Toranomon Hospital
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Tokyo, Japan, 181-8611
- Kyorin University Hospital
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Tokyo, Japan, 135-8550
- Cancer Institute Hospital of JFCR
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Tokyo, Japan, 113-8677
- Tokyo Metropolitan Komagome Hospital
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Yokohama, Japan, 241-8515
- Kanagawa Cancer Center
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Hyogo
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Amagasaki, Hyogo, Japan, 660-8550
- Amagasaki General Medical Center
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Ibaraki
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Tsukuba, Ibaraki, Japan, 305-8576
- University of tsukuba hospital
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Gyeonggi-do, Korea, Republic of
- National Cancer Center, Korea
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Seongnam, Korea, Republic of
- Seoul National University Bundang Hospital
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Seoul, Korea, Republic of
- Korea Cancer Center Hospital
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Seoul, Korea, Republic of
- Seoul National University College of Medicine
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Changhua, Taiwan
- Changhua Christian Hospital
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Kaohsiung, Taiwan
- Kaohsiung Medical University Chung-Ho Memorial Hospital
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Taipei, Taiwan
- National Taiwan University Hospital
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Taipei, Taiwan
- Sun Yat-Sen Cancer Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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
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
Exclusion Criteria:
- 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.
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Active Comparator: Placebo + Endocrine therapy
Endocrine therapy for 16 weeks plus placebo
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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.
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Active Comparator: Palbociclib + Endocrine therapy
Endocrine therapy for 16 weeks plus Palbociclib
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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 will be administered orally once a day for 21 days every 28-day cycle followed by 7 days off treatment
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Pre-operative Endocrine Prognostic Index (PEPI Score)
Time Frame: 4 months
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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
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EndoPredict™ EPclin Score
Time Frame: 4 months
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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
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Clinical Response Rate
Time Frame: 4 months
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Observing any reduction in largest tumor diameter on clinical breast examination and ultrasound imaging of breast and axilla after 4 months
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4 months
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Ki67 change
Time Frame: 4 months
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Drop in Ki67 index to less than or equal to 2.7%
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4 months
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pathological response rate
Time Frame: 4 months
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Evaluating the rate of pathological Complete Response based on assessment of surgical specimen
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4 months
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Breast conserving rate
Time Frame: 4 months
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Calculating the rate of breast conserving surgery based on the number of each surgery type
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4 months
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Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment as Assessed by CTCAE v4.03
Time Frame: 4 months
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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
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4 months
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Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: 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
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- OOTR-N016/KBCRN-B-003/HT-PAB
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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