Clinical Trials List
Protocol NumberA5481027
NCT Number(ClinicalTrials.gov Identfier)NCT02297438
2014-10-01 - 2025-12-31
Phase III
Terminated9
ICD-10C50.019
Malignant neoplasm of nipple and areola, unspecified female breast
A MULTICENTER, RANDOMIZED, DOUBLE-BLIND PHASE 3 STUDY OF PALBOCICLIB (ORAL CDK 4/6 INHIBITOR) PLUS LETROZOLE VERSUS PLACEBO PLUS LETROZOLE FOR THE TREATMENT OF PREVIOUSLY UNTREATED ASIAN POSTMENOPAUSAL WOMEN WITH ER (+), HER2 (-) ADVANCED BREAST CANCER
-
Trial Applicant
IQVIA RDS Taiwan Ltd.
-
Sponsor
Pfizer Inc.
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Principal Investigator
Co-Principal Investigator
- 張財旺 Division of General Surgery
- Wu-Chou Su Division of General Internal Medicine
- Wen-Pin Su Division of General Internal Medicine
- Shang-Yin Wu Division of General Internal Medicine
- Wei-Pang Chung Division of General Surgery
- Yu-Min Yeh Division of General Internal Medicine
- Yao-Lung Kuo Division of General Surgery
- Ya-Ting Hsu Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Ta-Chung Chao Division of Hematology & Oncology
- Yi-Fang Tsai Division of General Surgery
- 金光亮 Division of General Surgery
- Chun-Yu Liu Division of Hematology & Oncology
- 邱仁輝 Division of General Surgery
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- YEN-SHEN LU Division of Hematology & Oncology
- Wei-Wu Chen Division of Hematology & Oncology
- SUNG-HSIN KUO Division of Hematology & Oncology
- 羅喬 Division of General Surgery
- MING-YANG WANG Division of General Surgery
- 林柏翰 Division of General Internal Medicine
- 林璟宏 Division of Hematology & Oncology
- 張端瑩 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 林炯森 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- HWEI-CHUNG WANG 未分科
- Chih-Jung Chen 未分科
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- CHIA-CHUN KUO Division of Others -
- 謝瑞坤 Division of Hematology & Oncology
- 夏和雄 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Principal Investigator
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Mao-Chih Hsieh Division of General Surgery
- Chi-Long Chen Division of Radiation Therapy
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Terminated
Condition/Disease
breast cancer
Objectives
Primary Objective:
To compare the combination of Palbociclib plus letrozole with placebo plus letrozole
in term of progression-free survival (PFS) in Asian postmenopausal women with
ER(+)/HER2(-) advanced breast cancer (ABC) who have not received any prior
systemic anti-cancer therapy for advanced disease.
Secondary Objectives:
To compare Objective Response (OR), Duration of Response (DR), Disease Control
Rate (DCR), and Overall Survival (OS) between the treatment arms;
To evaluate the safeties and tolerability of the treatment arms;
To determine trough Palbociclib plasma concentration in this patient population and
explore the correlations between exposure and response and/or safety findings;To
compare health-related quality of life between the treatment arms;
To characterize alterations in genes, proteins, and RNAs relevant to the cell cycle,
drug targets, and tumor sensitivity and/or resistance in tumor tissues;
To explore the relationship between germline polymorphism in CDK6 gene and
palbociclib treatment related neutropenia.
Test Drug
Palbociclib
Active Ingredient
Palbociclib (PD-0332991)
Dosage Form
Oral Capsule
Dosage
75 mg/Capsule、100 mg/Capsule、125 mg/Capsule
Endpoints
Primary Endpoint
Progression-Free Survival (PFS) based on investigator’s assessment.
Secondary Endpoint(s)
Progression-Free Survival (PFS) based on blinded independent central review
(BICR);
090177e185960f7f\Approved\Approved On: 06-Aug-2014 17:22
Objective Response (OR)
Duration of Response (DR);
Disease Control Rate (DCR);
Overall Survival (OS);
1-year, 2-year, and 3-year Survival Probabilities;
Trough plasma concentration of Palbociclib;
Quality of life assessments: EuroQol (EQ-5D) Score (see Appendix 5) and Functional
Assessment of Cancer Therapy - Breast (FACT-B) (See Appendix 6);
Type, incidence, severity (as graded by NCI CTCAE v4.0), seriousness and
relationship to study medications of adverse events (AE) and any laboratory
abnormalities;
Tumor tissue biomarkers, including genes, proteins, and RNA expression (eg, ER,
Ki67).
Progression-Free Survival (PFS) based on investigator’s assessment.
Secondary Endpoint(s)
Progression-Free Survival (PFS) based on blinded independent central review
(BICR);
090177e185960f7f\Approved\Approved On: 06-Aug-2014 17:22
Objective Response (OR)
Duration of Response (DR);
Disease Control Rate (DCR);
Overall Survival (OS);
1-year, 2-year, and 3-year Survival Probabilities;
Trough plasma concentration of Palbociclib;
Quality of life assessments: EuroQol (EQ-5D) Score (see Appendix 5) and Functional
Assessment of Cancer Therapy - Breast (FACT-B) (See Appendix 6);
Type, incidence, severity (as graded by NCI CTCAE v4.0), seriousness and
relationship to study medications of adverse events (AE) and any laboratory
abnormalities;
Tumor tissue biomarkers, including genes, proteins, and RNA expression (eg, ER,
Ki67).
Inclution Criteria
1. Adult Asian women (ages 18-70 years, inclusive) with proven diagnosis of adenocarcinoma of
the breast with evidence of locoregionally recurrent or metastatic disease not amenable to
resection or radiation therapy with curative intent and for whom chemotherapy is not
clinically indicated. Sites in Taiwan will recruit subjects ≥20 years old only.
2. Documentation of histologically or cytologically confirmed diagnosis of estrogen-receptor
positive (ER+) breast cancer based on local laboratory results.
3. Previously untreated with any systemic anti-cancer therapy for their locoregionally recurrent
or metastatic ER+ disease.
4. Postmenopausal status defined as :
Prior bilateral surgical oophorectomy, or
Medically confirmed post-menopausal status defined as spontaneous cessation of
regular menses for at least 12 consecutive months or follicle-stimulating hormone
(FSH) and estradiol blood levels in their respective postmenopausal ranges with no
alternative pathological or physiological cause.
5. Measurable disease as defined per RECIST v.1.1 or bone-only disease. Tumor lesions
previously irradiated or subjected to other locoregional therapy will only be deemed
measurable if disease progression at the treated site after completion of therapy is clearly
documented.
6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1.
7. Adequate organ and bone marrow function defined as follows:
Absolute Neutrophil Count (ANC) ≥1,500/mm3
(1.5 x 109
/L);
Platelets ≥100,000/mm3
(100 x 109
/L);
Hemoglobin ≥9 g/dL (90 g/L);
Serum creatinine ≤1.5 x Upper Limit of Normal (ULN) or estimated creatinine
clearance ≥ 60 mL/min as calculated using the method standard for the institution;
Total serum bilirubin ≤1.5 x ULN (≤3.0 x ULN if Gilbert’s disease);
AST and/or ALT ≤3 x ULN (≤5.0 x ULN if liver metastases present);
Alkaline phosphatase ≤2.5 x ULN (≤5.0 x ULN if bone or liver metastases present).
8. Resolution of all acute toxic effects of prior anti-cancer therapy or surgical procedures to
NCI CTCAE version 4.0 Grade ≤1 (except alopecia or other toxicities not considered a safety
risk for the patient at investigator's discretion).
9. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and
other study procedures.
10. You must agree to provide tumor tissues for centralized retrospective confirmation of ER
status and to evaluate correlation between genes, proteins, and RNAs relevant to the cell
cycle pathways and sensitivity/resistance to the investigational agents. Freshly biopsied,
recurrent/metastatic tumor samples must be provided whenever possible. If such a biopsy is
not feasible or cannot be safely performed, then an archived tumor sample may be accepted.
In either case a formalin fixed, paraffin embedded (FFPE) block or 12 unstained FFPE slides
(highly recommend to submit tissue block or 12 unstained slides, but if there would be
technical difficulties or other issues refraining from obtaining tissue block or 12 unstained
slides, however, it is still mandatory to collect a minimum 7 unstained slides) are required
for patient participation.
11. Evidence of a personally signed and dated informed consent document indicating that the
patient has been informed of all pertinent aspects of the study.
the breast with evidence of locoregionally recurrent or metastatic disease not amenable to
resection or radiation therapy with curative intent and for whom chemotherapy is not
clinically indicated. Sites in Taiwan will recruit subjects ≥20 years old only.
2. Documentation of histologically or cytologically confirmed diagnosis of estrogen-receptor
positive (ER+) breast cancer based on local laboratory results.
3. Previously untreated with any systemic anti-cancer therapy for their locoregionally recurrent
or metastatic ER+ disease.
4. Postmenopausal status defined as :
Prior bilateral surgical oophorectomy, or
Medically confirmed post-menopausal status defined as spontaneous cessation of
regular menses for at least 12 consecutive months or follicle-stimulating hormone
(FSH) and estradiol blood levels in their respective postmenopausal ranges with no
alternative pathological or physiological cause.
5. Measurable disease as defined per RECIST v.1.1 or bone-only disease. Tumor lesions
previously irradiated or subjected to other locoregional therapy will only be deemed
measurable if disease progression at the treated site after completion of therapy is clearly
documented.
6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1.
7. Adequate organ and bone marrow function defined as follows:
Absolute Neutrophil Count (ANC) ≥1,500/mm3
(1.5 x 109
/L);
Platelets ≥100,000/mm3
(100 x 109
/L);
Hemoglobin ≥9 g/dL (90 g/L);
Serum creatinine ≤1.5 x Upper Limit of Normal (ULN) or estimated creatinine
clearance ≥ 60 mL/min as calculated using the method standard for the institution;
Total serum bilirubin ≤1.5 x ULN (≤3.0 x ULN if Gilbert’s disease);
AST and/or ALT ≤3 x ULN (≤5.0 x ULN if liver metastases present);
Alkaline phosphatase ≤2.5 x ULN (≤5.0 x ULN if bone or liver metastases present).
8. Resolution of all acute toxic effects of prior anti-cancer therapy or surgical procedures to
NCI CTCAE version 4.0 Grade ≤1 (except alopecia or other toxicities not considered a safety
risk for the patient at investigator's discretion).
9. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and
other study procedures.
10. You must agree to provide tumor tissues for centralized retrospective confirmation of ER
status and to evaluate correlation between genes, proteins, and RNAs relevant to the cell
cycle pathways and sensitivity/resistance to the investigational agents. Freshly biopsied,
recurrent/metastatic tumor samples must be provided whenever possible. If such a biopsy is
not feasible or cannot be safely performed, then an archived tumor sample may be accepted.
In either case a formalin fixed, paraffin embedded (FFPE) block or 12 unstained FFPE slides
(highly recommend to submit tissue block or 12 unstained slides, but if there would be
technical difficulties or other issues refraining from obtaining tissue block or 12 unstained
slides, however, it is still mandatory to collect a minimum 7 unstained slides) are required
for patient participation.
11. Evidence of a personally signed and dated informed consent document indicating that the
patient has been informed of all pertinent aspects of the study.
Exclusion Criteria
1. HER2-positive tumor as defined by documentation of erbB-2 gene amplification by FISH
(as defined by a HER2/CEP17 ratio ≥2) or chromogenic in situ hybridization (CISH, as
defined by the manufacturer’s kit instruction) or documentation of HER2-overexpression
by IHC (defined as IHC3+, or IHC2+ with FISH or CISH confirmation) based on local
laboratory results utilizing one of the sponsor-approved assays. If HER2 status is
unavailable or was determined using a test other than a sponsor-approved assay, then testing
must be performed/repeated using one of these assays prior to randomization. If tissue
sample from both primary and recurrent/metastatic tumors are available, HER2 assessment
from the most recent sample (ie, recurrent/metastatic sample) should be used to define
eligibility whenever feasible.
2. Patients with advanced, symptomatic, visceral spread, that are at risk of life-threatening
complications in the short term (including patients with massive uncontrolled effusions
[pleural, pericardial, peritoneal], pulmonary lymphangitis, and over 50% liver
involvement).
3. Known active uncontrolled or symptomatic CNS metastases, carcinomatous meningitis, or
leptomeningeal disease as indicated by clinical symptoms, cerebral edema, and/or
progressive growth. Patients with a history of CNS metastases or cord compression are
eligible if they have been definitively treated with local therapy (eg, radiotherapy,
stereotactic surgery) and are clinically stable off anticonvulsants and steroids for at least
4 weeks before randomization.
4. Prior neoadjuvant or adjuvant treatment with a non-steroidal aromatase inhibitor (ie,
anastrozole or letrozole) with disease recurrence while on or within 12 months of
completing treatment.
5. Prior treatment with any CDK4/6 inhibitor.
6. Patients treated within the last 7 days prior to randomization with:
Food or drugs that are known to be CYP3A4 inhibitors (ie, amprenavir, atazanavir,
boceprevir, clarithromycin, conivaptan, delavirdine, diltiazem, erythromycin,
fosamprenavir, indinavir, itraconazole, ketoconazole, lopinavir, mibefradil, miconazole,
nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin,
verapamil, voriconazole, and grapefruit or grapefruit juice);
Drugs that are known to be CYP3A4 inducers (ie, carbamazepine, felbamate,
nevirapine, phenobarbital, phenytoin, primidone, rifabutin, rifampin, rifapentin, and St.
John’s wort);
Drugs that are known to prolong the QT interval.
7. Major surgery, chemotherapy, radiotherapy, any investigational agents, or other anti-cancer
therapy within 2 weeks before randomization. Patients who received prior radiotherapy to
≥25% of bone marrow are not eligible independent of when it was received.
8. Diagnosis of any other malignancy within 3 years prior to randomization, except for
adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix.
9. Machine-read QTc >480 msec (based on the mean value of the triplicate Electrocardiogram,
ECGs), family or personal history of long or short QT syndrome, Brugada syndrome or
known history of QTc prolongation, or Torsade de Pointes (TdP).
10. Uncontrolled electrolyte disorders that can compound the effects of a QTc-prolonging drug
(eg, hypocalcemia, hypokalemia, hypomagnesemia).
11. Any of the following within 6 months of randomization: myocardial infarction,
severe/unstable angina, ongoing cardiac dysrhythmias of NCI CTCAE
version 4.0 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.
12. Active inflammatory bowel disease or chronic diarrhea, short bowel syndrome, or any upper
gastrointestinal surgery including gastric resection.
13. Known hypersensitivity to letrozole, or any of its excipients, or to any Palbociclib/placebo
excipients.
14. Known human immunodeficiency virus infection.
15. Other severe acute or chronic medical or psychiatric condition (including recent or active
suicidal ideation or behavior) or laboratory abnormality that may increase the risk
associated with study participation or investigational product administration or may
interfere with the interpretation of study results and, in the judgment of the investigator,
would make the patient inappropriate for entry into this study.
16. Patients who are investigational site staff members directly involved in the conduct of the
trial and their family members, site staff members otherwise supervised by the Investigator,
or subjects who are Pfizer employees directly involved in the conduct of the trial.
17. Participation in other studies involving investigational drug(s) (Phase 1-4) within 4 weeks
before the current study begins and/or during study participation in the active treatment
phase of the trial.
(as defined by a HER2/CEP17 ratio ≥2) or chromogenic in situ hybridization (CISH, as
defined by the manufacturer’s kit instruction) or documentation of HER2-overexpression
by IHC (defined as IHC3+, or IHC2+ with FISH or CISH confirmation) based on local
laboratory results utilizing one of the sponsor-approved assays. If HER2 status is
unavailable or was determined using a test other than a sponsor-approved assay, then testing
must be performed/repeated using one of these assays prior to randomization. If tissue
sample from both primary and recurrent/metastatic tumors are available, HER2 assessment
from the most recent sample (ie, recurrent/metastatic sample) should be used to define
eligibility whenever feasible.
2. Patients with advanced, symptomatic, visceral spread, that are at risk of life-threatening
complications in the short term (including patients with massive uncontrolled effusions
[pleural, pericardial, peritoneal], pulmonary lymphangitis, and over 50% liver
involvement).
3. Known active uncontrolled or symptomatic CNS metastases, carcinomatous meningitis, or
leptomeningeal disease as indicated by clinical symptoms, cerebral edema, and/or
progressive growth. Patients with a history of CNS metastases or cord compression are
eligible if they have been definitively treated with local therapy (eg, radiotherapy,
stereotactic surgery) and are clinically stable off anticonvulsants and steroids for at least
4 weeks before randomization.
4. Prior neoadjuvant or adjuvant treatment with a non-steroidal aromatase inhibitor (ie,
anastrozole or letrozole) with disease recurrence while on or within 12 months of
completing treatment.
5. Prior treatment with any CDK4/6 inhibitor.
6. Patients treated within the last 7 days prior to randomization with:
Food or drugs that are known to be CYP3A4 inhibitors (ie, amprenavir, atazanavir,
boceprevir, clarithromycin, conivaptan, delavirdine, diltiazem, erythromycin,
fosamprenavir, indinavir, itraconazole, ketoconazole, lopinavir, mibefradil, miconazole,
nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin,
verapamil, voriconazole, and grapefruit or grapefruit juice);
Drugs that are known to be CYP3A4 inducers (ie, carbamazepine, felbamate,
nevirapine, phenobarbital, phenytoin, primidone, rifabutin, rifampin, rifapentin, and St.
John’s wort);
Drugs that are known to prolong the QT interval.
7. Major surgery, chemotherapy, radiotherapy, any investigational agents, or other anti-cancer
therapy within 2 weeks before randomization. Patients who received prior radiotherapy to
≥25% of bone marrow are not eligible independent of when it was received.
8. Diagnosis of any other malignancy within 3 years prior to randomization, except for
adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix.
9. Machine-read QTc >480 msec (based on the mean value of the triplicate Electrocardiogram,
ECGs), family or personal history of long or short QT syndrome, Brugada syndrome or
known history of QTc prolongation, or Torsade de Pointes (TdP).
10. Uncontrolled electrolyte disorders that can compound the effects of a QTc-prolonging drug
(eg, hypocalcemia, hypokalemia, hypomagnesemia).
11. Any of the following within 6 months of randomization: myocardial infarction,
severe/unstable angina, ongoing cardiac dysrhythmias of NCI CTCAE
version 4.0 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.
12. Active inflammatory bowel disease or chronic diarrhea, short bowel syndrome, or any upper
gastrointestinal surgery including gastric resection.
13. Known hypersensitivity to letrozole, or any of its excipients, or to any Palbociclib/placebo
excipients.
14. Known human immunodeficiency virus infection.
15. Other severe acute or chronic medical or psychiatric condition (including recent or active
suicidal ideation or behavior) or laboratory abnormality that may increase the risk
associated with study participation or investigational product administration or may
interfere with the interpretation of study results and, in the judgment of the investigator,
would make the patient inappropriate for entry into this study.
16. Patients who are investigational site staff members directly involved in the conduct of the
trial and their family members, site staff members otherwise supervised by the Investigator,
or subjects who are Pfizer employees directly involved in the conduct of the trial.
17. Participation in other studies involving investigational drug(s) (Phase 1-4) within 4 weeks
before the current study begins and/or during study participation in the active treatment
phase of the trial.
The Estimated Number of Participants
-
Taiwan
16 participants
-
Global
330 participants
