Clinical Trials List
Protocol NumberD081CC00006
2014-05-01 - 2029-12-31
Phase III
Terminated12
ICD-10C50.919
Malignant neoplasm of unspecified site of unspecified female breast
ICD-9174.9
Malignant neoplasm of female breast, unspecified
A randomised, double-blind, parallel group, placebo-controlled multicentre Phase III study to assess the efficacy and safety of olaparib versus placebo as adjuvant treatment in patients with germline BRCA1/2 mutations and high risk HER2 negative primary breast cancer who have completed definitive local treatment and neoadjuvant or adjuvant chemotherapy
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Trial Applicant
-
Sponsor
AstraZeneca
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 戴明燊 Division of Hematology & Oncology
- 吳宜穎 Division of Hematology & Oncology
- 廖國秀 Division of General Surgery
- 何景良 Division of Hematology & Oncology
- 陳佳宏 Division of Hematology & Oncology
- Tsu-Yi Chao Division of Hematology & Oncology
- 黃子權 Division of Hematology & Oncology
- 陳宇欽 Division of Hematology & Oncology
- 高偉堯 Division of Hematology & Oncology
- 張平穎 Division of Hematology & Oncology
- 許桓銘 Division of General Surgery
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Yung-Chang Lin Division of Hematology & Oncology
- Hsien-Kun Chang Division of Hematology & Oncology
- 沈士哲 Division of General Surgery
- Wen-Chi Shen Division of Hematology & Oncology
- Chi-Chang Yu Division of General Surgery
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Chieh-Han Chuang Division of General Surgery
- 甘蓉瑜 Division of General Surgery
- Fu Ouyang Division of General Surgery
- Fang-Ming Chen Division of General Surgery
The Actual Total Number of Participants Enrolled
0 Terminated
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 陳威宇 Division of Hematology & Oncology
- Shang-Hung Chen Division of Hematology & Oncology
- 曹朝榮 Division of Hematology & Oncology
- 陳昭勳 Division of Hematology & Oncology
- 陳彥勳 Division of Hematology & Oncology
- 黃文聰 Division of Hematology & Oncology
- 林建良 Division of Hematology & Oncology
- 林明賢 Division of Hematology & Oncology
- 林正耀 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 賴鴻文 Division of General Surgery
- 曾信順 Division of General Surgery
- 蘇進成 Division of General Surgery
- Yao-Chung Wu Division of General Surgery
- 葉坤土 Division of Others
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 郭文宏 Division of General Surgery
- Wei-Wu Chen 無
- 林璟宏 Division of Hematology & Oncology
- 張端瑩 Division of Hematology & Oncology
- 蔡立威 無
- YEN-SHEN LU Division of Hematology & Oncology
- 林柏翰 Division of General Internal Medicine
- 羅喬 Division of General Surgery
- MING-YANG WANG Division of General Surgery
- 林季宏 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 金光亮 Division of General Surgery
- 邱仁輝 Division of General Surgery
- Chun-Yu Liu Division of Hematology & Oncology
- 林永慧 Division of Radiology
- Yi-Fang Tsai Division of General Surgery
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Sin-Syue Li Division of General Internal Medicine
- 張財旺 Division of General Surgery
- Ya-Ting Hsu Division of General Internal Medicine
- Yao-Lung Kuo Division of General Surgery
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Chih-Jung Chen Division of General Surgery
- Yao-Chung Wu Division of General Surgery
- Liang-Chih Liu Division of General Surgery
The Actual Total Number of Participants Enrolled
1 Stop recruiting
The Actual Total Number of Participants Enrolled
0 Terminated
Condition/Disease
primary breast cancer
Objectives
The primary objective is to assess the effect of adjuvant treatment with olaparib on Invasive Disease Free Survival (IDFS)
Test Drug
Olaparib
Active Ingredient
Olaparib
Dosage Form
tablet
Dosage
150 mg/ tablet 100 mg/tablet
Endpoints
Primary objective
The primary objective is to assess the effect of adjuvant treatment with olaparib on Invasive
Disease Free Survival (IDFS).
Secondary objectives
The secondary objectives of this study are:
1. To assess the effect of adjuvant treatment with olaparib on overall survival (OS)
2. To assess the effect of adjuvant treatment with olaparib on Distant Disease Free
Survival (DDFS)
3. To assess the effect of adjuvant treatment with olaparib on the incidence of new
invasive breast primary cancer and/or new epithelial ovarian cancer
4. To assess the effect of olaparib on patient reported outcomes using the FACIT
fatigue scale and EORTC QLQ-C30 QoL scale
5. To assess efficacy of olaparib in patients identified as having a deleterious or
suspected deleterious variant in either of the BRCA genes using variants identified
with current and future BRCA mutation assays (gene sequencing and large
rearrangement analysis)
The primary objective is to assess the effect of adjuvant treatment with olaparib on Invasive
Disease Free Survival (IDFS).
Secondary objectives
The secondary objectives of this study are:
1. To assess the effect of adjuvant treatment with olaparib on overall survival (OS)
2. To assess the effect of adjuvant treatment with olaparib on Distant Disease Free
Survival (DDFS)
3. To assess the effect of adjuvant treatment with olaparib on the incidence of new
invasive breast primary cancer and/or new epithelial ovarian cancer
4. To assess the effect of olaparib on patient reported outcomes using the FACIT
fatigue scale and EORTC QLQ-C30 QoL scale
5. To assess efficacy of olaparib in patients identified as having a deleterious or
suspected deleterious variant in either of the BRCA genes using variants identified
with current and future BRCA mutation assays (gene sequencing and large
rearrangement analysis)
Inclution Criteria
For inclusion in the study patients should fulfil the following criteria:
1. *Provision of informed consent prior to any study specific procedures
2. *Female or male patients must be 18 years of age
3. Histologically confirmed non-metastatic primary triple negative invasive
adenocarcinoma of the breast that is at surgery:
either axillary node-positive (any tumour size) or axillary node-negative with
primary tumour > 2cm for patients who received adjuvant chemotherapy
or showing evidence of non pCR for patients who received neoadjuvant
chemotherapy
4. Invasive TNBC defined as:
ER and PR negative (not eligible for endocrine therapy) defined as IHC nuclear
staining <1% AND
HER2 negative (not eligible for anti-HER2 therapy) defined as:
o IHC 0, 1+ without ISH OR
o IHC 2+ and ISH non-amplified with ratio less than 2.0 and if reported
average HER2 copy number < 6 signals/cells OR
o ISH non-amplified with ratio less than 2.0 and if reported average HER2
copy number < 6 signals/cells without IHC)
5. Documented mutation in BRCA1 or BRCA2 that is predicted to be deleterious or
suspected deleterious (known or predicted to be detrimental/lead to loss of function)
(See Section 3.1).
6. Completed adequate breast and axilla surgery defined as:
The inked margins of breast conservation surgery or mastectomy must be
histologically free of invasive breast cancer and ductal carcinoma in situ with
the exception of the posterior margin if this margin is the pectoralis major
fascia or the anterior margin if this is the dermis. Patients with resection
margins positive for lobular carcinoma in situ are eligible.
Patients with breast conservation must have adjuvant radiotherapy. Patients
having mastectomy should have adjuvant radiotherapy according to
international guidelines (St Gallen/ASCO/ESTRO).
Adjuvant Group:
Sentinel lymph node biopsy alone if negative or if lymph node(s) only contain
micrometastases (2.0 mm) OR positive sentinel lymph node biopsy followed
by axillary node clearance or axillary nodal radiotherapy
Neoadjuvant group:
If sentinel lymph node biopsy before neoadjuvant chemotherapy: sentinel
lymph node biopsy alone if negative or if lymph node(s) only contain
micrometastases (2.0 mm) OR positive sentinel lymph node biopsy followed
by axillary node clearance or axillary nodal radiotherapy following completion
of neoadjuvant chemotherapy
If sentinel lymph node biopsy after neoadjuvant chemotherapy: Sentinel lymph
node biopsy alone if negative OR positive sentinel lymph node biopsy
followed by axillary node clearance.
7. Completed at least 6 cycles neoadjuvant or adjuvant chemotherapy containing
anthracyclines, taxanes or the combination of both. Prior platinum as potentially
curative treatment for prior cancer (e.g. ovarian) or as adjuvant or neoadjuvant
treatment for breast cancer is allowed
8. Patients must have normal organ and bone marrow function measured within 28
days prior to randomisation as defined below:
Haemoglobin 10.0 g/dL with no blood transfusions in the past 28 days
Absolute neutrophil count (ANC) 1.5 x 109
/L
Platelet count 100 x 109
/L
Total Bilirubin ULN (institutional upper limit of normal) except elevated
total bilirubin <1.5 x ULN due to Gilbert’s disease or similar syndrome
involving slow conjugation of bilirubin
AST (SGOT)/ALT (SGPT) 2.5 x ULN
ALP 2.5 x ULN
Patients with screening ALT/AST or ALP above institutional upper limit of normal
should have liver ultrasound or CT/ MRI prior to randomisation. Screening bone
scan is required if ALP and/or corrected calcium level are above the institutional
upper limit. (Note PET CT scan may be used as an alternative imaging techniques).
9. Serum creatinine 1.5 x ULN
10. ECOG performance status 0-1
11. *Postmenopausal or evidence of non-childbearing status for women of childbearing
potential: negative urine or serum pregnancy test within 7 days prior to
randomisation
Postmenopausal is defined as:
Age > 60 yrs
Age < 60 and amenorrheic for 1 year or more in the absence of chemotherapy
and/or hormonal treatment
LH, FSH and plasma oestradiol levels in the post menopausal range for women
under 60
radiation-induced oophorectomy with last menses >1 year ago
or surgical sterilisation (bilateral oophorectomy or hysterectomy)
12. *Patient is willing and able to comply with the protocol for the duration of the study
including undergoing treatment and scheduled visits and examinations
13. Formalin fixe
1. *Provision of informed consent prior to any study specific procedures
2. *Female or male patients must be 18 years of age
3. Histologically confirmed non-metastatic primary triple negative invasive
adenocarcinoma of the breast that is at surgery:
either axillary node-positive (any tumour size) or axillary node-negative with
primary tumour > 2cm for patients who received adjuvant chemotherapy
or showing evidence of non pCR for patients who received neoadjuvant
chemotherapy
4. Invasive TNBC defined as:
ER and PR negative (not eligible for endocrine therapy) defined as IHC nuclear
staining <1% AND
HER2 negative (not eligible for anti-HER2 therapy) defined as:
o IHC 0, 1+ without ISH OR
o IHC 2+ and ISH non-amplified with ratio less than 2.0 and if reported
average HER2 copy number < 6 signals/cells OR
o ISH non-amplified with ratio less than 2.0 and if reported average HER2
copy number < 6 signals/cells without IHC)
5. Documented mutation in BRCA1 or BRCA2 that is predicted to be deleterious or
suspected deleterious (known or predicted to be detrimental/lead to loss of function)
(See Section 3.1).
6. Completed adequate breast and axilla surgery defined as:
The inked margins of breast conservation surgery or mastectomy must be
histologically free of invasive breast cancer and ductal carcinoma in situ with
the exception of the posterior margin if this margin is the pectoralis major
fascia or the anterior margin if this is the dermis. Patients with resection
margins positive for lobular carcinoma in situ are eligible.
Patients with breast conservation must have adjuvant radiotherapy. Patients
having mastectomy should have adjuvant radiotherapy according to
international guidelines (St Gallen/ASCO/ESTRO).
Adjuvant Group:
Sentinel lymph node biopsy alone if negative or if lymph node(s) only contain
micrometastases (2.0 mm) OR positive sentinel lymph node biopsy followed
by axillary node clearance or axillary nodal radiotherapy
Neoadjuvant group:
If sentinel lymph node biopsy before neoadjuvant chemotherapy: sentinel
lymph node biopsy alone if negative or if lymph node(s) only contain
micrometastases (2.0 mm) OR positive sentinel lymph node biopsy followed
by axillary node clearance or axillary nodal radiotherapy following completion
of neoadjuvant chemotherapy
If sentinel lymph node biopsy after neoadjuvant chemotherapy: Sentinel lymph
node biopsy alone if negative OR positive sentinel lymph node biopsy
followed by axillary node clearance.
7. Completed at least 6 cycles neoadjuvant or adjuvant chemotherapy containing
anthracyclines, taxanes or the combination of both. Prior platinum as potentially
curative treatment for prior cancer (e.g. ovarian) or as adjuvant or neoadjuvant
treatment for breast cancer is allowed
8. Patients must have normal organ and bone marrow function measured within 28
days prior to randomisation as defined below:
Haemoglobin 10.0 g/dL with no blood transfusions in the past 28 days
Absolute neutrophil count (ANC) 1.5 x 109
/L
Platelet count 100 x 109
/L
Total Bilirubin ULN (institutional upper limit of normal) except elevated
total bilirubin <1.5 x ULN due to Gilbert’s disease or similar syndrome
involving slow conjugation of bilirubin
AST (SGOT)/ALT (SGPT) 2.5 x ULN
ALP 2.5 x ULN
Patients with screening ALT/AST or ALP above institutional upper limit of normal
should have liver ultrasound or CT/ MRI prior to randomisation. Screening bone
scan is required if ALP and/or corrected calcium level are above the institutional
upper limit. (Note PET CT scan may be used as an alternative imaging techniques).
9. Serum creatinine 1.5 x ULN
10. ECOG performance status 0-1
11. *Postmenopausal or evidence of non-childbearing status for women of childbearing
potential: negative urine or serum pregnancy test within 7 days prior to
randomisation
Postmenopausal is defined as:
Age > 60 yrs
Age < 60 and amenorrheic for 1 year or more in the absence of chemotherapy
and/or hormonal treatment
LH, FSH and plasma oestradiol levels in the post menopausal range for women
under 60
radiation-induced oophorectomy with last menses >1 year ago
or surgical sterilisation (bilateral oophorectomy or hysterectomy)
12. *Patient is willing and able to comply with the protocol for the duration of the study
including undergoing treatment and scheduled visits and examinations
13. Formalin fixe
Exclusion Criteria
Patients should not enter the study if any of the following exclusion criteria are fulfilled:
1. Involvement in the planning and/or conduct of the study.
2. BRCA 1 and/or BRCA2 mutations that are considered to be non detrimental (e.g.,
“Variants of uncertain clinical significance” or “Variant of unknown significance”
or “Variant, favour polymorphism” or “benign polymorphism” etc.).
3. *Previous randomisation in the present study.
4. *Evidence of metastatic breast cancer. Patient considered at high risk of having
disseminated disease (i.e those with clinical N2-3 or pathological N1-3 or locally
advanced disease) must have a CT/MRI scan of the Thorax/Abdomen/Pelvis or any
other area as clinically indicated and a bone scan at any point prior to
randomisation. (Note PET CT scan may be used as an alternative imaging
techniques and precludes the need for bone scan)
5. *Exposure to an investigational product within 30 days or five half lives (whichever
is the longer) prior to randomisation.
6. *Any previous treatment with a PARP inhibitor, including olaparib and/or known
hypersensitivity to any of the excipients of study treatment.
7. *Patients with second primary cancer, EXCEPTIONS: adequately treated nonmelanoma skin cancer, curatively treated in situ cancer of the cervix, Ductal
Carcinoma in situ (DCIS) of the breast, stage 1 grade 1 endometrial carcinoma, or
other solid tumours including lymphomas (without bone marrow involvement)
curatively treated with no evidence of disease for 5 years prior to randomization.
More than one course of chemotherapy for previous malignancies (e.g: breast
cancer or ovarian cancer > 5 years ago treated with adjuvant chemotherapy)
8. Resting ECG with QTc > 470 msec detected on 2 or more time points within a 24
hour period or family history of long QT syndrome. If ECG demonstrates QTc
>470 msec, patient will be eligible only if repeat ECG demonstrates QTc 470
msec.
9. Patients receiving systemic chemotherapy within 3 weeks prior to start of study
treatment.
10. Patients receiving adjuvant radiotherapy within 2 weeks prior to start of study
treatment
11. Concomitant use of known potent CYP3A4 inhibitors such as ketoconazole,
itraconazole, ritonavir, indinavir, saquinavir, telithromycin, clarithromycin and
nelfinavir. For further detail refer to Appendix I.
12. Persistent toxicities (CTCAE grade 2) caused by previous cancer therapy,
excluding alopecia and CTCAE grade 2 peripheral neuropathy.
13. *Patients with myelodysplastic syndrome/ treatment related acute myeloid
leukaemia (t-AML).
14. Major surgery within 2 weeks of starting study treatment: patients must have
recovered from any effects of any major surgery.
15. Patients considered a poor medical risk due to a serious, uncontrolled medical
disorder, non-malignant systemic disease or active, uncontrolled infection.
Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent
(within 3 months) myocardial infarction, uncontrolled major seizure disorder,
extensive bilateral lung disease on High Resolution Computed Tomography scan or
any psychiatric disorder that prohibits obtaining informed consent.
16. *Patients unable to swallow orally administered medication and patients with
gastrointestinal disorders likely to interfere with absorption of the study medication.
17. Pregnant or breastfeeding women.
18. * Patients with known active Hepatitis B or C or HIV
19. *Previous allogeneic bone marrow transplant.
20. *Whole blood transfusions in the last 120 days prior to entry to the study which
may interfere with gBRCA testing (packed red blood cells and platelet transfusions
are acceptable, for timing refer to inclusion criteria no.8)
1. Involvement in the planning and/or conduct of the study.
2. BRCA 1 and/or BRCA2 mutations that are considered to be non detrimental (e.g.,
“Variants of uncertain clinical significance” or “Variant of unknown significance”
or “Variant, favour polymorphism” or “benign polymorphism” etc.).
3. *Previous randomisation in the present study.
4. *Evidence of metastatic breast cancer. Patient considered at high risk of having
disseminated disease (i.e those with clinical N2-3 or pathological N1-3 or locally
advanced disease) must have a CT/MRI scan of the Thorax/Abdomen/Pelvis or any
other area as clinically indicated and a bone scan at any point prior to
randomisation. (Note PET CT scan may be used as an alternative imaging
techniques and precludes the need for bone scan)
5. *Exposure to an investigational product within 30 days or five half lives (whichever
is the longer) prior to randomisation.
6. *Any previous treatment with a PARP inhibitor, including olaparib and/or known
hypersensitivity to any of the excipients of study treatment.
7. *Patients with second primary cancer, EXCEPTIONS: adequately treated nonmelanoma skin cancer, curatively treated in situ cancer of the cervix, Ductal
Carcinoma in situ (DCIS) of the breast, stage 1 grade 1 endometrial carcinoma, or
other solid tumours including lymphomas (without bone marrow involvement)
curatively treated with no evidence of disease for 5 years prior to randomization.
More than one course of chemotherapy for previous malignancies (e.g: breast
cancer or ovarian cancer > 5 years ago treated with adjuvant chemotherapy)
8. Resting ECG with QTc > 470 msec detected on 2 or more time points within a 24
hour period or family history of long QT syndrome. If ECG demonstrates QTc
>470 msec, patient will be eligible only if repeat ECG demonstrates QTc 470
msec.
9. Patients receiving systemic chemotherapy within 3 weeks prior to start of study
treatment.
10. Patients receiving adjuvant radiotherapy within 2 weeks prior to start of study
treatment
11. Concomitant use of known potent CYP3A4 inhibitors such as ketoconazole,
itraconazole, ritonavir, indinavir, saquinavir, telithromycin, clarithromycin and
nelfinavir. For further detail refer to Appendix I.
12. Persistent toxicities (CTCAE grade 2) caused by previous cancer therapy,
excluding alopecia and CTCAE grade 2 peripheral neuropathy.
13. *Patients with myelodysplastic syndrome/ treatment related acute myeloid
leukaemia (t-AML).
14. Major surgery within 2 weeks of starting study treatment: patients must have
recovered from any effects of any major surgery.
15. Patients considered a poor medical risk due to a serious, uncontrolled medical
disorder, non-malignant systemic disease or active, uncontrolled infection.
Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent
(within 3 months) myocardial infarction, uncontrolled major seizure disorder,
extensive bilateral lung disease on High Resolution Computed Tomography scan or
any psychiatric disorder that prohibits obtaining informed consent.
16. *Patients unable to swallow orally administered medication and patients with
gastrointestinal disorders likely to interfere with absorption of the study medication.
17. Pregnant or breastfeeding women.
18. * Patients with known active Hepatitis B or C or HIV
19. *Previous allogeneic bone marrow transplant.
20. *Whole blood transfusions in the last 120 days prior to entry to the study which
may interfere with gBRCA testing (packed red blood cells and platelet transfusions
are acceptable, for timing refer to inclusion criteria no.8)
The Estimated Number of Participants
-
Taiwan
40 participants
-
Global
1800 participants
