Clinical Trials List
Protocol NumberNCCH1607
NCT Number(ClinicalTrials.gov Identfier)NCT03423199
2018-02-01 - 2025-09-30
Phase III
Recruiting3
ICD-10C50
Malignant neoplasm of breast
ICD-9174.9
Malignant neoplasm of female breast, unspecified
Asian, International, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial of Tamoxifen With or Without Palbociclib +/- Goserelin in Women with Hormone Receptor-Positive, HER2-Negative Advanced or Metastatic Breast Cancer 賀爾蒙受體陽性、HER2 陰性之晚期或轉移性乳癌婦女，使用 Tamoxifen 併用或不併用 Palbociclib +/- Goserelin 之亞洲跨國、多中心、隨機、雙盲、安慰劑對照第三期試驗
-
Trial Applicant
GEORGE CLINICAL ASIA PACIFIC LIMITED
-
Sponsor
National Cancer Center, Japan
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 邱仁輝 Division of General Surgery
- Chun-Yu Liu Division of Hematology & Oncology
- Yi-Fang Tsai Division of General Surgery
- 賴亦貞 Division of Radiology
- 金光亮 Division of General Surgery
- Ta-Chung Chao Division of Hematology & Oncology
- 林燕淑 Division of General Surgery
The Actual Total Number of Participants Enrolled
1 Recruiting
Audit
None
Co-Principal Investigator
- 林季宏 Division of Hematology & Oncology
- Wei-Wu Chen Division of Hematology & Oncology
- 張端瑩 Division of Hematology & Oncology
- MING-YANG WANG Division of General Surgery
The Actual Total Number of Participants Enrolled
0 Recruiting
Audit
None
Condition/Disease
Advanced or Metastatic Breast Cancer
Objectives
Primary Objective
• To demonstrate the superiority of palbociclib in combination with
tamoxifen (with or without goserelin) over tamoxifen (with or without
goserelin) alone in prolonging investigator-assessed PFS in women with
HR-positive/HER2-negative advanced or metastatic breast cancer,
regardless of their menopausal status.
Test Drug
Ibrance / Palbociclib
Active Ingredient
Palbociclib
Dosage Form
capsule
Dosage
75 mg, 100 mg, 125 mg
Endpoints
Primary Endpoint
• Progression-Free Survival (PFS) as assessed by the investigator.
• Progression-Free Survival (PFS) as assessed by the investigator.
Inclution Criteria
Patients must meet all of the following inclusion criteria to be eligible for
enrollment into the study:
1. Women 18 years of age or older at informed consent.
2. Histologically or cytologically proven diagnosis of breast cancer with
evidence of locally advanced or metastatic disease, not amenable to
resection or radiation therapy with curative intent.
3. Documentation of ER-positive and/or PgR-positive tumor (1% positive
stained cells, or Allred score of 3 or more) based on most recent tumor
biopsy (unless bone-only disease) utilizing an assay consistent with local
standards.
4. Documented HER2-negative tumor based on local testing on most recent
tumor biopsy (unless bone-only disease) utilizing an assay consistent with
local standards.
5. Patients will be candidates to receive tamoxifen as first-line or second-line
endocrine treatment for their advanced/metastatic disease. Thus, patients
must satisfy the following criteria for prior therapy:
• Previously untreated with any endocrine therapy for their HRpositive/HER2-negative advanced/metastatic disease;
If patients have received adjuvant endocrine therapy, patients must
satisfy the following criteria.
➢ Progressed after 12 months or more since the last dosing of
adjuvant therapy with tamoxifen or other SERM (eg. toremifene
or raloxifene, etc) with or without LH-RH agonist;
OR
➢ Progressed during treatment or after adjuvant therapy with an
AI, regardless of the period from adjuvant endocrine therapy
until disease progression.
OR
• Progressed while on or within 3 month after the end of prior one
regimen of AI or endocrine treatment other than tamoxifen or other
SERM for advanced/metastatic breast cancer
One previous line of chemotherapy for advanced/metastatic disease is
allowed in addition to endocrine therapy.
6. Measurable disease or non-measurable disease as defined by RECIST
ver.1.1. Tumor lesions previously irradiated or subjected to other loco
regional therapy will only be deemed measurable if progression at the
treated site after completion of therapy is clearly documented.
7. Eastern Cooperative Oncology Group (ECOG) PS 0-1.
8. Adequate organ and marrow function defined as follows:
• 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 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).
9. Resolution of all adverse effects of prior therapy or surgical procedures to
National Cancer Institute (NCI) CTCAE ver.4.0 Grade 1 (except
alopecia).
10. Evidence of a personally signed and dated informed consent document
indicating that the patient (or a legal representative) has been informed of
all pertinent aspects of the study.
11. Patients who are willing and able to comply with scheduled visits,
treatment plan, laboratory tests, and other study procedures.
enrollment into the study:
1. Women 18 years of age or older at informed consent.
2. Histologically or cytologically proven diagnosis of breast cancer with
evidence of locally advanced or metastatic disease, not amenable to
resection or radiation therapy with curative intent.
3. Documentation of ER-positive and/or PgR-positive tumor (1% positive
stained cells, or Allred score of 3 or more) based on most recent tumor
biopsy (unless bone-only disease) utilizing an assay consistent with local
standards.
4. Documented HER2-negative tumor based on local testing on most recent
tumor biopsy (unless bone-only disease) utilizing an assay consistent with
local standards.
5. Patients will be candidates to receive tamoxifen as first-line or second-line
endocrine treatment for their advanced/metastatic disease. Thus, patients
must satisfy the following criteria for prior therapy:
• Previously untreated with any endocrine therapy for their HRpositive/HER2-negative advanced/metastatic disease;
If patients have received adjuvant endocrine therapy, patients must
satisfy the following criteria.
➢ Progressed after 12 months or more since the last dosing of
adjuvant therapy with tamoxifen or other SERM (eg. toremifene
or raloxifene, etc) with or without LH-RH agonist;
OR
➢ Progressed during treatment or after adjuvant therapy with an
AI, regardless of the period from adjuvant endocrine therapy
until disease progression.
OR
• Progressed while on or within 3 month after the end of prior one
regimen of AI or endocrine treatment other than tamoxifen or other
SERM for advanced/metastatic breast cancer
One previous line of chemotherapy for advanced/metastatic disease is
allowed in addition to endocrine therapy.
6. Measurable disease or non-measurable disease as defined by RECIST
ver.1.1. Tumor lesions previously irradiated or subjected to other loco
regional therapy will only be deemed measurable if progression at the
treated site after completion of therapy is clearly documented.
7. Eastern Cooperative Oncology Group (ECOG) PS 0-1.
8. Adequate organ and marrow function defined as follows:
• 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 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).
9. Resolution of all adverse effects of prior therapy or surgical procedures to
National Cancer Institute (NCI) CTCAE ver.4.0 Grade 1 (except
alopecia).
10. Evidence of a personally signed and dated informed consent document
indicating that the patient (or a legal representative) has been informed of
all pertinent aspects of the study.
11. Patients who are willing and able to comply with scheduled visits,
treatment plan, laboratory tests, and other study procedures.
Exclusion Criteria
Patients presenting with any of the following will not be included in the study:
1. Prior treatment with any CDK inhibitor, or tamoxifen (patients who
progressed >12 months after the completion of adjuvant therapy with
tamoxifen with or without LH-RH agonist are eligible), or with
everolimus, or any agent whose mechanism of action is to inhibit the
PI3K-mTOR pathway.
2. Patients with advanced/metastatic, symptomatic, visceral spread, that are at
risk of life-threatening complications in the short term (“visceral crisis”,
including patients with massive uncontrolled effusions [pleural,
pericardial, peritoneal], pulmonary lymphangitis, pulmonary metastasis
with dyspnea on exertion, and over 50% liver involvement).
3. Known active uncontrolled or symptomatic Central Nervous System
(CNS) metastases, carcinomatous meningitis, or leptomeningeal disease as
indicated by at least of the following: clinical symptoms, cerebral edema,
or progressive growth. Patients with a history of CNS metastases or cord
compression are eligible if they have been definitively treated (eg,
radiotherapy, stereotactic surgery) and are clinically stable off
anticonvulsants and steroids for at least 4 weeks before randomization.
4. Current use (including within last 10 days prior to randomization) of food
or drugs known to be strong or moderate CYP3A4 and/or CYP2D6
inhibitors, drugs known to be strong or moderate CYP3A4 inducers, and drugs that are known to prolong the QT interval. Topical use of these
agents is allowed, if necessary.
5. Patients who received other SERM (eg. toremifene or raloxifene, etc) or
hormone replacement therapy (HRT) within 12 months prior to
randomization. Prior oral contraceptives are allowed.
6. Major surgery, chemotherapy, endocrine therapy, radiotherapy, 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.
7. 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 esophagus, stomach, colon or cervix.
8. QTc interval >480 msec (based on the mean value of the triplicate ECGs),
family or personal history of long or short QT syndrome, Brugada
syndrome or known history of QTc prolongation or Torsade de Pointes.
9. Any of the following within 6 months prior to randomization: myocardial
infarction, severe/unstable angina, ongoing cardiac dysrhythmias of NCI
CTCAE ver.4.0 Grade 2, atrial fibrillation of any grade,
coronary/peripheral artery bypass graft, symptomatic congestive heart
failure, cerebrovascular accident including transient ischemic attack,
symptomatic deep vein thrombosis or symptomatic pulmonary embolism.
10. Impairment of gastro-intestinal (GI) function or GI disease that may
significantly alter the absorption of palbociclib/placebo and tamoxifen,
such as history of GI surgery with may result in intestinal blind loops and
patients with clinically significant gastroparesis, short bowel syndrome,
unresolved nausea, vomiting, active inflammatory bowel disease or
diarrhea of CTCAE ver.4.0 Grade 2.
11. Prior hematopoietic stem cell or bone marrow transplantation.
12. Known abnormalities in coagulation such as bleeding diathesis, or
treatment with anticoagulants precluding subcutaneous injection of
goserelin (if applicable).
13. Known or possible hypersensitivity to tamoxifen, goserelin, any of their
excipients or to any palbociclib/placebo excipients.
14. Known human immunodeficiency virus infection.
15. Patients with positive hepatitis B surface antigen (HBsAg) test and/or
detectable hepatitis B virus (HBV) DNA in serum are recommended to
receive antiviral prophylaxis against HBV reactivation. Patients with
positive hepatitis B core antibosy (anti-HBc) and negative HbsAg/undetectable HBV DNA are recommended to receive periodic
monitoring of HBV DNA.
16. 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 enrollment into this study.
17. 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 and 90 days in her partner after the last dose
of investigational drug (palbociclib/placebo) and tamoxifen.
18. 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 patients who are Pfizer employees
directly involved in the conduct of the trial for palbociclib.
19. Participation in other studies involving investigational drug(s) (phases 1-4)
within 4 weeks before randomization.
1. Prior treatment with any CDK inhibitor, or tamoxifen (patients who
progressed >12 months after the completion of adjuvant therapy with
tamoxifen with or without LH-RH agonist are eligible), or with
everolimus, or any agent whose mechanism of action is to inhibit the
PI3K-mTOR pathway.
2. Patients with advanced/metastatic, symptomatic, visceral spread, that are at
risk of life-threatening complications in the short term (“visceral crisis”,
including patients with massive uncontrolled effusions [pleural,
pericardial, peritoneal], pulmonary lymphangitis, pulmonary metastasis
with dyspnea on exertion, and over 50% liver involvement).
3. Known active uncontrolled or symptomatic Central Nervous System
(CNS) metastases, carcinomatous meningitis, or leptomeningeal disease as
indicated by at least of the following: clinical symptoms, cerebral edema,
or progressive growth. Patients with a history of CNS metastases or cord
compression are eligible if they have been definitively treated (eg,
radiotherapy, stereotactic surgery) and are clinically stable off
anticonvulsants and steroids for at least 4 weeks before randomization.
4. Current use (including within last 10 days prior to randomization) of food
or drugs known to be strong or moderate CYP3A4 and/or CYP2D6
inhibitors, drugs known to be strong or moderate CYP3A4 inducers, and drugs that are known to prolong the QT interval. Topical use of these
agents is allowed, if necessary.
5. Patients who received other SERM (eg. toremifene or raloxifene, etc) or
hormone replacement therapy (HRT) within 12 months prior to
randomization. Prior oral contraceptives are allowed.
6. Major surgery, chemotherapy, endocrine therapy, radiotherapy, 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.
7. 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 esophagus, stomach, colon or cervix.
8. QTc interval >480 msec (based on the mean value of the triplicate ECGs),
family or personal history of long or short QT syndrome, Brugada
syndrome or known history of QTc prolongation or Torsade de Pointes.
9. Any of the following within 6 months prior to randomization: myocardial
infarction, severe/unstable angina, ongoing cardiac dysrhythmias of NCI
CTCAE ver.4.0 Grade 2, atrial fibrillation of any grade,
coronary/peripheral artery bypass graft, symptomatic congestive heart
failure, cerebrovascular accident including transient ischemic attack,
symptomatic deep vein thrombosis or symptomatic pulmonary embolism.
10. Impairment of gastro-intestinal (GI) function or GI disease that may
significantly alter the absorption of palbociclib/placebo and tamoxifen,
such as history of GI surgery with may result in intestinal blind loops and
patients with clinically significant gastroparesis, short bowel syndrome,
unresolved nausea, vomiting, active inflammatory bowel disease or
diarrhea of CTCAE ver.4.0 Grade 2.
11. Prior hematopoietic stem cell or bone marrow transplantation.
12. Known abnormalities in coagulation such as bleeding diathesis, or
treatment with anticoagulants precluding subcutaneous injection of
goserelin (if applicable).
13. Known or possible hypersensitivity to tamoxifen, goserelin, any of their
excipients or to any palbociclib/placebo excipients.
14. Known human immunodeficiency virus infection.
15. Patients with positive hepatitis B surface antigen (HBsAg) test and/or
detectable hepatitis B virus (HBV) DNA in serum are recommended to
receive antiviral prophylaxis against HBV reactivation. Patients with
positive hepatitis B core antibosy (anti-HBc) and negative HbsAg/undetectable HBV DNA are recommended to receive periodic
monitoring of HBV DNA.
16. 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 enrollment into this study.
17. 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 and 90 days in her partner after the last dose
of investigational drug (palbociclib/placebo) and tamoxifen.
18. 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 patients who are Pfizer employees
directly involved in the conduct of the trial for palbociclib.
19. Participation in other studies involving investigational drug(s) (phases 1-4)
within 4 weeks before randomization.
The Estimated Number of Participants
-
Taiwan
18 participants
-
Global
180 participants
