Clinical Trials List
Protocol NumberAFT-05, ABCSG 42, BIG 14-03
NCT Number(ClinicalTrials.gov Identfier)NCT02513394
2017-02-01 - 2027-02-01
Phase III
Terminated5
ICD-10C50
Malignant neoplasm of breast
PALbociclib CoLlaborative Adjuvant Study: A Randomized Phase III Trial of Palbociclib With Standard Adjuvant Endocrine Therapy Versus Standard Adjuvant Endocrine Therapy Alone for Hormone Receptor Positive (HR+) / Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Early Breast Cancer
-
Trial Applicant
Syneos Health
-
Sponsor
ABCSG GmbH/Alliance Foundation Trials, LLC.
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- 邱仁輝 Division of General Surgery
- Yi-Fang Tsai Division of General Surgery
- Ta-Chung Chao Division of Hematology & Oncology
- 金光亮 Division of General Surgery
- Chun-Yu Liu Division of Hematology & Oncology
- 林燕淑 Division of General Surgery
The Actual Total Number of Participants Enrolled
8 Stop recruiting
Audit
None
Co-Principal Investigator
- Kuo-Ting Lee Division of General Surgery
- Ya-Ting Hsu Division of General Internal Medicine
- Ya-Ping Chen Division of General Internal Medicine
- Jui-Hung Tsai Division of General Internal Medicine
- Wu-Chou Su Division of General Internal Medicine
- Zhu-Jun Loh Division of General Surgery
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Audit
None
Co-Principal Investigator
Audit
None
Co-Principal Investigator
- 蔡立威 Division of General Surgery
- 張端瑩 Division of Hematology & Oncology
- 羅喬 Division of General Surgery
- YEN-SHEN LU Division of Hematology & Oncology
- MING-YANG WANG Division of General Surgery
- SUNG-HSIN KUO Division of Hematology & Oncology
- 郭文宏 Division of General Surgery
- 林柏翰 Division of General Internal Medicine
- Wei-Wu Chen Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Audit
None
Co-Principal Investigator
- Chieh-Han Chuang Division of General Surgery
- Fang-Ming Chen Division of General Surgery
- Fu Ouyang Division of General Surgery
- 甘蓉瑜 Division of General Surgery
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Condition/Disease
Hormone receptor positive (HR+)/human epidermal growth factor receptor 2 (HER2)-negative early breast cancer
Objectives
Primary Objective
To compare invasive disease-free survival (iDFS) for the combination
of at least 5 years endocrine therapy and 2-year palbociclib treatment
versus at least 5 years endocrine therapy alone in patients with
histologically confirmed HR+/HER2- invasive early breast cancer (EBC).
Secondary Objectives
-To compare the following endpoints: iDFS excluding second primary
cancers of non-breast origin, distant recurrence-free survival (DRFS),
locoregional recurrences-free survival (LRRFS), and overall survival (OS).
-To compare the safety of 2 years of palbociclib with adjuvant endocrine
therapy versus adjuvant endocrine therapy alone.
Test Drug
Ibrance
Active Ingredient
Palbociclib
Dosage Form
capsule
Dosage
75, 100, 125
Endpoints
Primary Endpoint:
The primary endpoint is invasive disease-free survival (iDFS),
defined according to STEEP criteria as the composite of: local/regional invasive
ipsilateral recurrence, contralateral invasive breast cancer, distant recurrence, second
primary invasive*
cancer of non-breast origin or death from any cause. Surviving patients
who are event-free will be censored at: the date of last disease assessment, or withdrawal
of consent to be followed, whichever occurs first.
*Second non-breast primary cancers also include e.g. leukemia, myelodysplasia,
plasmocytoma but do not include any new in situ carcinomas of any site or nonmetastatic non-melanomatous skin cancers.
Secondary Endpoints:
Invasive disease-free survival (iDFS) excluding second primary cancers of non-breast
origin. Second primary cancers of non-breast origin will not be considered as events for
this endpoint. Surviving patients who are event-free will be censored at: the date of last
disease assessment, or withdrawal of consent to be followed, whichever occurs first.
The primary endpoint is invasive disease-free survival (iDFS),
defined according to STEEP criteria as the composite of: local/regional invasive
ipsilateral recurrence, contralateral invasive breast cancer, distant recurrence, second
primary invasive*
cancer of non-breast origin or death from any cause. Surviving patients
who are event-free will be censored at: the date of last disease assessment, or withdrawal
of consent to be followed, whichever occurs first.
*Second non-breast primary cancers also include e.g. leukemia, myelodysplasia,
plasmocytoma but do not include any new in situ carcinomas of any site or nonmetastatic non-melanomatous skin cancers.
Secondary Endpoints:
Invasive disease-free survival (iDFS) excluding second primary cancers of non-breast
origin. Second primary cancers of non-breast origin will not be considered as events for
this endpoint. Surviving patients who are event-free will be censored at: the date of last
disease assessment, or withdrawal of consent to be followed, whichever occurs first.
Inclution Criteria
Inclusion Criteria
Please note that waivers to eligibility requirements are not allowed.
Patients must meet the following criteria for study entry:
Patient/Disease Specifics
(1) Signed informed consent obtained prior to any study specific assessments and procedures.
(2) Age ≥18 years (or per national guidelines).
(3) Premenopausal and postmenopausal women or men with Stage II (Stage IIA
limited to a maximum of 1000 patients) or Stage III early invasive breast cancer
per AJCC (American Joint Committee on Cancer) Breast Cancer Staging version
7 / UICC (Union for International Cancer Control)54. Baseline staging to
document absence of metastatic disease is not required, however is recommended
as determined by institutional practice (in patients where there may be a
reasonable suspicion of advanced disease e.g., large tumors, clinically positive
axillary lymph nodes, signs and symptoms). If performed, reports of these
examinations must be available. Examination type for staging, i.e. X-ray,
sonography, bone scan, CT, MRI, and/or PET-CT, is at the discretion of the investigator.
If neoadjuvant systemic therapy was received (either chemotherapy or
endocrine therapy), either initial clinical stage (determined by physical
and/or radiologic examination) or post-operative pathologic stage can be
used for eligibility purposes, with the higher stage determining eligibility.
(4) Patients with multicentric and/or multifocal and/or bilateral early invasive breast
cancer whose histopathologically examined tumors all meet pathologic criteria
for ER+ and/or PR+ and HER2-.
(5) Patients must have histologically confirmed hormone receptor positive (ER+
and/or PR+), HER2-, early invasive breast cancer. ER, PR and HER2
measurements should be performed according to institutional guidelines, in a
CLIA-approved setting in the US or certified laboratories for Non-US regions.
Cut-off values for positive/negative staining should be in accordance with current
ASCO/CAP (American Society of Clinical Oncology/College of American
Pathologists) guidelines55
. Patients with equivocal HER2 in situ hybridization
results according to current ASCO/CAP guidelines are eligible, as long as they
have not received and are not scheduled to receive anti-HER2 treatment. Testing
may occur on diagnostic core or surgical tumor tissue.
(6) Patients must have undergone breast surgery for the current malignancy.
(7) A formalin-fixed paraffin-embedded (FFPE) tumor tissue block must be
transmitted to a central sample repository and confirmation of receipt must be
available prior to randomization. For details please refer to section 8.2.
(8) ECOG performance status 0-1.
(9) Patients must be able and willing to swallow and retain oral medication without a
condition that would interfere with enteric absorption.
(10) Serum or urine pregnancy test must be negative within 7 days of randomization,
in women of childbearing potential. Pregnancy testing does not need to be
pursued in patients who are judged as postmenopausal before randomization, as
determined by local practice, or who have undergone bilateral oophorectomy,
total hysterectomy, or bilateral tubal ligation. Women of childbearing potential
and male patients randomized into treatment Arm A or B must use adequate
contraception for the duration of protocol treatment and for 6 months after the
last treatment with palbociclib if they are in arm A. Adequate contraception is
defined as one highly effective form (i.e. abstinence, (fe)male sterilization) OR
two effective forms (e.g. non-hormonal IUD and condom / occlusive cap with
spermicidal foam / gel / film / cream / suppository).
Prior Treatment Specifics
(11) Patients may or may not have received neo/adjuvant therapy, but must be after
last dose of chemotherapy and/or biologic therapy and must have sufficient
resolution of side effects per physician assessment at the time of randomization.
(12) Patients may or may not have received breast/axilla/ post-mastectomy chest wall
radiotherapy, but must be after last dose of radiotherapy and must have sufficient
resolution of side effects per physician assessment at the time of randomization.
(13) Patients must have sufficient resolution of any surgical side effects from the last
surgery per physician assessment, with no active wound healing complications at
the time of randomization.
(14) Patients must either be initiating or have already started adjuvant hormonal
treatment. Patients may already have initiated endocrine therapy at the time of
randomization, but randomization must take place within 12 months of date of
histological diagnosis and within 6 months of initiating standard adjuvant
endocrine therapy. Patients who received neoadjuvant endocrine therapy are
eligible as long as they are enrolled within 12 months of initial histological
diagnosis and after completing no more than 6 months of adjuvant endocrine
therapy. Patients may be receiving either tamoxifen or aromatase inhibitor (AI:
letrozole, anastrozole, or exemestane). For premenopausal patients and men,
concurrent LHRH agonist use is allowable and may also be ongoing at the time
of randomization.
Baseline Body Function Specifics
(15) Absolute neutrophil count ≥ 1,500/mm3.
(16) Platelets ≥ 100,000/mm3.
(17) Hemoglobin ≥ 10g/dL.
(18) Total serum bilirubin ≤ ULN; or total bilirubin ≤ 3.0 × ULN with direct bilirubin
within normal range in patients with documented Gilbert’s Syndrome.
(19) Aspartate amino transferase (AST or SGOT) and alanine amino transferase (ALT
or SGPT) ≤ 1.5 × institutional ULN.
(20) Serum creatinine within normal institutional limits or creatinine clearance ≥ 60
mL/min/1.73 m2
for patients with serum creatinine levels above institutional ULN.
Please note that waivers to eligibility requirements are not allowed.
Patients must meet the following criteria for study entry:
Patient/Disease Specifics
(1) Signed informed consent obtained prior to any study specific assessments and procedures.
(2) Age ≥18 years (or per national guidelines).
(3) Premenopausal and postmenopausal women or men with Stage II (Stage IIA
limited to a maximum of 1000 patients) or Stage III early invasive breast cancer
per AJCC (American Joint Committee on Cancer) Breast Cancer Staging version
7 / UICC (Union for International Cancer Control)54. Baseline staging to
document absence of metastatic disease is not required, however is recommended
as determined by institutional practice (in patients where there may be a
reasonable suspicion of advanced disease e.g., large tumors, clinically positive
axillary lymph nodes, signs and symptoms). If performed, reports of these
examinations must be available. Examination type for staging, i.e. X-ray,
sonography, bone scan, CT, MRI, and/or PET-CT, is at the discretion of the investigator.
If neoadjuvant systemic therapy was received (either chemotherapy or
endocrine therapy), either initial clinical stage (determined by physical
and/or radiologic examination) or post-operative pathologic stage can be
used for eligibility purposes, with the higher stage determining eligibility.
(4) Patients with multicentric and/or multifocal and/or bilateral early invasive breast
cancer whose histopathologically examined tumors all meet pathologic criteria
for ER+ and/or PR+ and HER2-.
(5) Patients must have histologically confirmed hormone receptor positive (ER+
and/or PR+), HER2-, early invasive breast cancer. ER, PR and HER2
measurements should be performed according to institutional guidelines, in a
CLIA-approved setting in the US or certified laboratories for Non-US regions.
Cut-off values for positive/negative staining should be in accordance with current
ASCO/CAP (American Society of Clinical Oncology/College of American
Pathologists) guidelines55
. Patients with equivocal HER2 in situ hybridization
results according to current ASCO/CAP guidelines are eligible, as long as they
have not received and are not scheduled to receive anti-HER2 treatment. Testing
may occur on diagnostic core or surgical tumor tissue.
(6) Patients must have undergone breast surgery for the current malignancy.
(7) A formalin-fixed paraffin-embedded (FFPE) tumor tissue block must be
transmitted to a central sample repository and confirmation of receipt must be
available prior to randomization. For details please refer to section 8.2.
(8) ECOG performance status 0-1.
(9) Patients must be able and willing to swallow and retain oral medication without a
condition that would interfere with enteric absorption.
(10) Serum or urine pregnancy test must be negative within 7 days of randomization,
in women of childbearing potential. Pregnancy testing does not need to be
pursued in patients who are judged as postmenopausal before randomization, as
determined by local practice, or who have undergone bilateral oophorectomy,
total hysterectomy, or bilateral tubal ligation. Women of childbearing potential
and male patients randomized into treatment Arm A or B must use adequate
contraception for the duration of protocol treatment and for 6 months after the
last treatment with palbociclib if they are in arm A. Adequate contraception is
defined as one highly effective form (i.e. abstinence, (fe)male sterilization) OR
two effective forms (e.g. non-hormonal IUD and condom / occlusive cap with
spermicidal foam / gel / film / cream / suppository).
Prior Treatment Specifics
(11) Patients may or may not have received neo/adjuvant therapy, but must be after
last dose of chemotherapy and/or biologic therapy and must have sufficient
resolution of side effects per physician assessment at the time of randomization.
(12) Patients may or may not have received breast/axilla/ post-mastectomy chest wall
radiotherapy, but must be after last dose of radiotherapy and must have sufficient
resolution of side effects per physician assessment at the time of randomization.
(13) Patients must have sufficient resolution of any surgical side effects from the last
surgery per physician assessment, with no active wound healing complications at
the time of randomization.
(14) Patients must either be initiating or have already started adjuvant hormonal
treatment. Patients may already have initiated endocrine therapy at the time of
randomization, but randomization must take place within 12 months of date of
histological diagnosis and within 6 months of initiating standard adjuvant
endocrine therapy. Patients who received neoadjuvant endocrine therapy are
eligible as long as they are enrolled within 12 months of initial histological
diagnosis and after completing no more than 6 months of adjuvant endocrine
therapy. Patients may be receiving either tamoxifen or aromatase inhibitor (AI:
letrozole, anastrozole, or exemestane). For premenopausal patients and men,
concurrent LHRH agonist use is allowable and may also be ongoing at the time
of randomization.
Baseline Body Function Specifics
(15) Absolute neutrophil count ≥ 1,500/mm3.
(16) Platelets ≥ 100,000/mm3.
(17) Hemoglobin ≥ 10g/dL.
(18) Total serum bilirubin ≤ ULN; or total bilirubin ≤ 3.0 × ULN with direct bilirubin
within normal range in patients with documented Gilbert’s Syndrome.
(19) Aspartate amino transferase (AST or SGOT) and alanine amino transferase (ALT
or SGPT) ≤ 1.5 × institutional ULN.
(20) Serum creatinine within normal institutional limits or creatinine clearance ≥ 60
mL/min/1.73 m2
for patients with serum creatinine levels above institutional ULN.
Exclusion Criteria
Exclusion Criteria
Patients who meet any of the following criteria will be excluded from study entry:
(1) Concurrent therapy with other Investigational Products.
(2) Prior therapy with any CDK inhibitor.
(3) Patients with Stage I or IV breast cancer are not eligible. Baseline staging to
document absence of metastatic disease is not required, however is recommended
as determined by institutional practice (in patients where there may be a
reasonable suspicion of advanced disease e.g., large tumors, clinically positive
axillary lymph nodes, signs and symptoms). If performed, reports of these
examinations must be available. Examination type for staging, i.e. X-ray,
sonography, bone scan, CT, MRI, and/or PET-CT, is at the discretion of the investigator.
(4) History of allergic reactions attributed to compounds of chemical or biologic
composition similar to palbociclib.
(5) Patients receiving any medications or substances that are potent inhibitors or
inducers of CYP3A isoenzymes within 7 days of randomization (see Section
9.5.2.1 for list of CYP3A inhibitors and inducers).
(6) Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, diabetes, or psychiatric illness/social situations that would limit
compliance with study requirements. Ability to comply with study requirements
is to be assessed by each investigator at the time of screening for study participation.
(7) Pregnant women, or women of childbearing potential without a negative
pregnancy test (serum or urine) within 7 days prior to randomization, irrespective
of the method of contraception used, are excluded from this study because the
effect of palbociclib on a developing fetus is unknown. Breastfeeding must be
discontinued prior to study entry.
(8) Patients with a history of any malignancy are ineligible except for the following
circumstances:
Patients with a malignancy history other than invasive breast cancer are
eligible if they have been disease-free for at least 5 years and are deemed by
the investigator to be at low risk for recurrence of that malignancy.
Patients with the following cancers are eligible, even if diagnosed and
treated within the past 5 years: ductal carcinoma in situ of the breast,
cervical cancer in situ, and non-metastatic non-melanomatous skin cancers.
(9) Patients are not eligible if they have previously received endocrine therapy
within 5 years prior to diagnosis of the current malignancy. This includes use for
prophylactic reasons, including treatment of osteoporosis or cancer prevention
with tamoxifen, raloxifene or AI. Patients may concurrently receive
bisphosphonates or rank ligand inhibitors while on this study if necessary for
treatment or prevention of osteopenia or osteoporosis.
(10) Patients on combination antiretroviral therapy, i.e. those who are HIV-positive,
are ineligible because of the potential for pharmacokinetic interactions or
increased immunosuppression with palbociclib.
(11) Patients with clinically significant history of liver disease, including viral or other
known hepatitis, current alcohol abuse, or cirrhosis, etc.
(12) Patients receiving concurrent exogenous hormone therapy (hormone replacement
therapy, oral or any other hormonal contraceptives such as hormonal
contraceptive coil, etc.) are not eligible but topical vaginal estrogen therapy is allowable.
Patients who meet any of the following criteria will be excluded from study entry:
(1) Concurrent therapy with other Investigational Products.
(2) Prior therapy with any CDK inhibitor.
(3) Patients with Stage I or IV breast cancer are not eligible. Baseline staging to
document absence of metastatic disease is not required, however is recommended
as determined by institutional practice (in patients where there may be a
reasonable suspicion of advanced disease e.g., large tumors, clinically positive
axillary lymph nodes, signs and symptoms). If performed, reports of these
examinations must be available. Examination type for staging, i.e. X-ray,
sonography, bone scan, CT, MRI, and/or PET-CT, is at the discretion of the investigator.
(4) History of allergic reactions attributed to compounds of chemical or biologic
composition similar to palbociclib.
(5) Patients receiving any medications or substances that are potent inhibitors or
inducers of CYP3A isoenzymes within 7 days of randomization (see Section
9.5.2.1 for list of CYP3A inhibitors and inducers).
(6) Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, diabetes, or psychiatric illness/social situations that would limit
compliance with study requirements. Ability to comply with study requirements
is to be assessed by each investigator at the time of screening for study participation.
(7) Pregnant women, or women of childbearing potential without a negative
pregnancy test (serum or urine) within 7 days prior to randomization, irrespective
of the method of contraception used, are excluded from this study because the
effect of palbociclib on a developing fetus is unknown. Breastfeeding must be
discontinued prior to study entry.
(8) Patients with a history of any malignancy are ineligible except for the following
circumstances:
Patients with a malignancy history other than invasive breast cancer are
eligible if they have been disease-free for at least 5 years and are deemed by
the investigator to be at low risk for recurrence of that malignancy.
Patients with the following cancers are eligible, even if diagnosed and
treated within the past 5 years: ductal carcinoma in situ of the breast,
cervical cancer in situ, and non-metastatic non-melanomatous skin cancers.
(9) Patients are not eligible if they have previously received endocrine therapy
within 5 years prior to diagnosis of the current malignancy. This includes use for
prophylactic reasons, including treatment of osteoporosis or cancer prevention
with tamoxifen, raloxifene or AI. Patients may concurrently receive
bisphosphonates or rank ligand inhibitors while on this study if necessary for
treatment or prevention of osteopenia or osteoporosis.
(10) Patients on combination antiretroviral therapy, i.e. those who are HIV-positive,
are ineligible because of the potential for pharmacokinetic interactions or
increased immunosuppression with palbociclib.
(11) Patients with clinically significant history of liver disease, including viral or other
known hepatitis, current alcohol abuse, or cirrhosis, etc.
(12) Patients receiving concurrent exogenous hormone therapy (hormone replacement
therapy, oral or any other hormonal contraceptives such as hormonal
contraceptive coil, etc.) are not eligible but topical vaginal estrogen therapy is allowable.
The Estimated Number of Participants
-
Taiwan
115 participants
-
Global
4600 participants
