Clinical Trials List
Protocol NumberOOTR-N016/ KBCRN-B-003/ HT-PAB
NCT Number(ClinicalTrials.gov Identfier)NCT03969121
2019-07-01 - 2021-12-23
Phase III
Recruiting3
Terminated1
ICD-10C50.919
Malignant neoplasm of unspecified site of unspecified female breast
ICD-9174.9
Malignant neoplasm of female breast, unspecified
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
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Trial Applicant
EPS International Holdings Co., Ltd.
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Sponsor
Kyoto Breast Cancer Research Network(KBCRN)
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- MING-YANG WANG Division of General Surgery
- 張端瑩 Division of Hematology & Oncology
- YEN-SHEN LU Division of Hematology & Oncology
- 羅喬 Division of General Surgery
- Wei-Wu Chen Division of Hematology & Oncology
- 蔡立威 Division of General Surgery
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Chieh-Han Chuang Division of General Surgery
- Chung-Liang Li Division of General Surgery
- Fang-Ming Chen Division of General Surgery
- Junping Shiau Shiau Division of General Surgery
- 甘蓉瑜 Division of General Surgery
- Fu Ouyang Division of General Surgery
- 巫承哲 Division of General Surgery
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Condition/Disease
Primary Breast Cancer
Objectives
Primary Objective
To evaluate the efficacy of the pre-operative use of hormonal therapy plus palbociclib vs. hormonal therapy plus placebo as measured by:
●PEPI
●EndoPredict™ EPclin Score
Secondary Objectives
■ To evaluate Clinical Response Rate (CRR) as the most important secondary endpoint
■ To evaluate the drop in Ki67 index ≤ 2.7%
■ To evaluate the rate of pathological CR (pCR)
■To evaluate Breast conserving rate (BCR)
■To evaluate the toxicity profile
■To obtain pre-treatment (core biopsy), after 2 week treatment (core biopsy, optional) and post-treatment (surgical specimen) tumor, blood and urine samples from patients for translational studies
Test Drug
Ibrance
Active Ingredient
Palbociclib
Dosage Form
capsule
Dosage
75,100,125
Endpoints
Primary Outcome Measures :
Pre-operative Endocrine Prognostic Index (PEPI Score) [ Time Frame: 4 months ]
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.
EndoPredict™ EPclin Score [ Time Frame: 4 months ]
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.
Secondary Outcome Measures :
Clinical Response Rate [ Time Frame: 4 months ]
Observing any reduction in largest tumor diameter on clinical breast examination and ultrasound imaging of breast and axilla after 4 months
Ki67 change [ Time Frame: 4 months ]
Drop in Ki67 index to less than or equal to 2.7%
pathological response rate [ Time Frame: 4 months ]
Evaluating the rate of pathological Complete Response based on assessment of surgical specimen
Breast conserving rate [ Time Frame: 4 months ]
Calculating the rate of breast conserving surgery based on the number of each surgery type
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 ]
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
Pre-operative Endocrine Prognostic Index (PEPI Score) [ Time Frame: 4 months ]
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.
EndoPredict™ EPclin Score [ Time Frame: 4 months ]
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.
Secondary Outcome Measures :
Clinical Response Rate [ Time Frame: 4 months ]
Observing any reduction in largest tumor diameter on clinical breast examination and ultrasound imaging of breast and axilla after 4 months
Ki67 change [ Time Frame: 4 months ]
Drop in Ki67 index to less than or equal to 2.7%
pathological response rate [ Time Frame: 4 months ]
Evaluating the rate of pathological Complete Response based on assessment of surgical specimen
Breast conserving rate [ Time Frame: 4 months ]
Calculating the rate of breast conserving surgery based on the number of each surgery type
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 ]
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
Inclution Criteria
Inclusion Criteria
1. Pre/peri- or post-menopausal women 18 years and older (or local legal age,
whichever is higher)
2. Primary tumor greater than 2 cm in diameter
3. Histologically proven invasive breast cancer
4. Positive hormone receptor (ER and/or PgR ≥ Allred 3)
5. Negative HER-2 receptor
6. Ki67 index equal to or greater than 14% (Ki67 ≥ 14%) by central assessment
7. Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤ 1 orKarnofsky performance status ≥ 70%
8. No previous history of radiotherapy or systemic therapy including chemotherapy
and hormone therapy for breast cancer
9. 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).
10. Able to give written informed consent form
11. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures
1. Pre/peri- or post-menopausal women 18 years and older (or local legal age,
whichever is higher)
2. Primary tumor greater than 2 cm in diameter
3. Histologically proven invasive breast cancer
4. Positive hormone receptor (ER and/or PgR ≥ Allred 3)
5. Negative HER-2 receptor
6. Ki67 index equal to or greater than 14% (Ki67 ≥ 14%) by central assessment
7. Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤ 1 orKarnofsky performance status ≥ 70%
8. No previous history of radiotherapy or systemic therapy including chemotherapy
and hormone therapy for breast cancer
9. 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).
10. Able to give written informed consent form
11. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures
Exclusion Criteria
1. Male
2. Locally advanced breast cancer (T3N1 or Any T4 or Any N2, N3), or distant metastasis
3. Multifocal or multicentric breast cancer
4. Prior treatment with chemotherapy, radiotherapy and/or endocrine therapy
5. Previous use of SERMs such as raloxifene.
6. Prior therapy with any CDK4/6 inhibitor or with everolimus, or any agent whose
mechanism of action is to inhibit the PI3K-mTOR pathway.
7. 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
8. Major surgery within 3 weeks of first study treatment
9. 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, ciprofloxacin, clarithromycin, conivaptan, cobicistat, crizotinib, cyclosporine, darunavir, diltiazem, dronedarone, elvitegravir, erythromycin, fluconazole,
fosamprenavir, imatinib, indinavir, isavuconazole, istradefylline, itraconazole,ketoconazole, letermovir, lopinavir, mibefradil, miconazole, nefazodone,
nelfinavir, nilotinib, posaconazole, ritonavir, saquinavir, schisandra sphenanthera 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, rifampin, rifapentin, and St. John’s wort);
10. Any of the following in the previous 6 months of randomization: myocardial infarction, 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 including transient ischemic attack, or symptomatic pulmonary embolism
11. Family or personal history of long or short QT syndrome, Brugada syndrome or
known history of QTc prolongation, or Torsade de Pointes (TdP).
12. Uncontrolled electrolyte disorders (eg, hypocalcemia, hypokalemia, hypomagnesemia) that can compound the effects of a QTc-prolonging drug.
13. Active inflammatory bowel disease or chronic diarrhea. Short bowel syndrome.
Upper gastrointestinal surgery including gastric resection.
14. Prior hematopoietic stem cell or bone marrow transplantation.
15. Known abnormalities in coagulation such as bleeding diathesis, or treatment with
anticoagulants precluding subcutaneous injections of leuprorelin or goserelin.
16. Hepatitis B and/or hepatitis C carriers (unless with normal hepatic function)
17. Known human immunodeficiency virus (HIV) infection
18. Known hypersensitivity to anti-aromatase drugs, tamoxifen or any cell cycle inhibitor.
19. 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 nonhormonal contraception throughout the study and continue for at least 21 days in
patients and 90 days in her partner after the last dose of investigational drug.
20. Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that would impart, in the judgment of the investigator, excess risk associated 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
21. Patients who are investigational site staff members or relatives of those site staff members or patients who are the sponsor employees directly involved in the conduct of the trial.
22. Participation in other studies involving investigational drug (s) (Phases 1-4) within 2 weeks before randomization and/or during participation in the active treatment phase of the trial.
2. Locally advanced breast cancer (T3N1 or Any T4 or Any N2, N3), or distant metastasis
3. Multifocal or multicentric breast cancer
4. Prior treatment with chemotherapy, radiotherapy and/or endocrine therapy
5. Previous use of SERMs such as raloxifene.
6. Prior therapy with any CDK4/6 inhibitor or with everolimus, or any agent whose
mechanism of action is to inhibit the PI3K-mTOR pathway.
7. 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
8. Major surgery within 3 weeks of first study treatment
9. 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, ciprofloxacin, clarithromycin, conivaptan, cobicistat, crizotinib, cyclosporine, darunavir, diltiazem, dronedarone, elvitegravir, erythromycin, fluconazole,
fosamprenavir, imatinib, indinavir, isavuconazole, istradefylline, itraconazole,ketoconazole, letermovir, lopinavir, mibefradil, miconazole, nefazodone,
nelfinavir, nilotinib, posaconazole, ritonavir, saquinavir, schisandra sphenanthera 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, rifampin, rifapentin, and St. John’s wort);
10. Any of the following in the previous 6 months of randomization: myocardial infarction, 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 including transient ischemic attack, or symptomatic pulmonary embolism
11. Family or personal history of long or short QT syndrome, Brugada syndrome or
known history of QTc prolongation, or Torsade de Pointes (TdP).
12. Uncontrolled electrolyte disorders (eg, hypocalcemia, hypokalemia, hypomagnesemia) that can compound the effects of a QTc-prolonging drug.
13. Active inflammatory bowel disease or chronic diarrhea. Short bowel syndrome.
Upper gastrointestinal surgery including gastric resection.
14. Prior hematopoietic stem cell or bone marrow transplantation.
15. Known abnormalities in coagulation such as bleeding diathesis, or treatment with
anticoagulants precluding subcutaneous injections of leuprorelin or goserelin.
16. Hepatitis B and/or hepatitis C carriers (unless with normal hepatic function)
17. Known human immunodeficiency virus (HIV) infection
18. Known hypersensitivity to anti-aromatase drugs, tamoxifen or any cell cycle inhibitor.
19. 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 nonhormonal contraception throughout the study and continue for at least 21 days in
patients and 90 days in her partner after the last dose of investigational drug.
20. Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that would impart, in the judgment of the investigator, excess risk associated 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
21. Patients who are investigational site staff members or relatives of those site staff members or patients who are the sponsor employees directly involved in the conduct of the trial.
22. Participation in other studies involving investigational drug (s) (Phases 1-4) within 2 weeks before randomization and/or during participation in the active treatment phase of the trial.
The Estimated Number of Participants
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Taiwan
38 participants
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Global
200 participants
