Clinical Trials List
Protocol NumberD3615C00001
NCT Number(ClinicalTrials.gov Identfier)NCT04305496
2020-05-01 - 2025-06-30
Phase III
Recruiting9
ICD-10C50.911
Malignant neoplasm of unspecified site of right female breast
ICD-10C50.912
Malignant neoplasm of unspecified site of left female breast
ICD-10C50.919
Malignant neoplasm of unspecified site of unspecified female breast
ICD-10Z51.12
Encounter for antineoplastic immunotherapy
ICD-9174.9
Malignant neoplasm of female breast, unspecified
A Phase III Double-blind Randomised Study Assessing the Efficacy and Safety of Capivasertib + Fulvestrant Versus Placebo + Fulvestrant as Treatment for Locally Advanced (Inoperable) or Metastatic Hormone Receptor Positive, Human Epidermal Growth Factor Receptor 2 Negative (HR+/HER2-) Breast Cancer Following Recurrence or Progression On or After Treatment With an Aromatase Inhibitor
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Trial Applicant
COVANCE TAIWAN SERVICES LIMITED
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Sponsor
AstraZeneca AB
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Chih-Jung Chen 無
- Liang-Chih Liu 無
- 黃至豪 無
- Chen-Teng Wu 無
- Yao-Chung Wu 無
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
Principal Investigator
Co-Principal Investigator
- 林燕淑 無
- Chi-Cheng Huang 無
- Yi-Fang Tsai 無
- 賴亦貞 無
- 邱仁輝 無
- Chun-Yu Liu 無
- Jiun-I Lai 無
- Ling-Ming Tseng 無
- Ta-Chung Chao 無
- 馮晉榮 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Mengting Peng 無
- 周旭桓 無
- Wen-Ling Kuo 無
- Chan-Keng Yang 無
- Chi-Chang Yu 無
- Wen-Chi Shen 無
- 沈士哲 無
- Yung-Chang Lin 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Kuo-Ting Lee 無
- 楊舜如 無
- Zhu-Jun Loh 無
- Ya-Ting Hsu 無
- Chun-Hui Lee 無
- Ya-Ping Chen 無
- Yao-Lung Kuo 無
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
Principal Investigator
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Meng-Jer Hsieh 無
- 洪朝明 無
- 蔡郁棻 無
- 裴松南 無
- 李蕙鳴 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 陳怡君 無
- 林柏翰 無
- Wei-Wu Chen 無
- 羅喬 無
- 張端瑩 無
- WEI-LI MA 無
- 林季宏 無
- MING-YANG WANG 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
advanced or metastatic breast cancer
Objectives
Phase III, double-blind, randomised study assessing the efficacy of capivasertib + fulvestrant vs placebo + fulvestrant for the treatment of patients with locally advanced (inoperable) or metastatic Hormone Receptor Positive, Human Epidermal Growth Factor Receptor 2 Negative (HR+/HER2-) breast cancer following recurrence or progression on or after aromatase inhibitor (AI) therapy.
To compare the effect of capivasertib + fulvestrant relative to placebo + fulvestrant by assessment of PFS in the overall population.
Test Drug
Capivasertib
Active Ingredient
Capivasertib (AZD5363)
Dosage Form
film-coated tablet
Dosage
160mg 及 200mg
Endpoints
Primary Outcome Measures :
Progression-Free Survival (PFS) in the overall population [ Time Frame: The time from date of randomisation to the date of progression or death due to any cause, whichever occurs earlier, up to approximately 51 months ]
Progression-Free Survival by investigator assessment (in accordance with RECIST 1.1)
Secondary Outcome Measures :
PFS in PIK3CA/AKT1/PTEN-altered subgroup [ Time Frame: The time from date of randomisation to the date of progression or death due to any cause, whichever occurs earlier, up to approximately 51 months ]
Progression-Free Survival by investigator assessment (in accordance with RECIST 1.1)
Overall Survival (OS) [ Time Frame: The time from date of randomisation to the date of death due to any cause up to 51 months ]
Overall Survival (OS)
Investigator assessment of PFS2 [ Time Frame: The time from the date of randomisation to the date of progression subsequent to the first subsequent therapy, or death due to any cause, whichever occurs earlier, up to approximately 51 months ]
PFS2 - time from randomisation to second progression by investigator assessment
Response Rate (ORR) [ Time Frame: Up to Approximately 51 months ]
percentage of patients with at least one investigator-assessed visit response of complete or partial response (as assessed by the investigator, using RECIST 1.1)
Duration of Response (DoR) [ Time Frame: Up to Approximately 51 months ]
time from the date of first documented response until date of documented progression (as assessed by the investigator, using RECIST 1.1) or death in the absence of disease progression
Clinical Benefit Rate (CBR) [ Time Frame: Up to Approximately 51 months ]
number of patients with complete or partial response or with stable disease maintained ≥24 weeks after randomisation (as assessed by the investigator, using RECIST 1.1)
ocurrence/frequency of AEs and its relationship to study drugs (safety and tolerability) [ Time Frame: Up to Approximately 51 months ]
AEs graded according to the National Cancer Institute (NCI CTCAE)
plasma concentration of capivasertib [ Time Frame: Minimum plasma concentration (Cmin), plasma concentration 1 hour post-dose (C1h) and 4 hours post-dose (C4h) during cycles 1 and 2 (each cycle is 28 days) ]
plasma concentration of capivasertib pre-dose and post-dose (C1h and C4h) in the overall population
EORTC QLQ BR23(European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire breast cancer specific module) [ Time Frame: Up to Approximately 51 months ]
The self-administered instrument includes 23-items and yields 5 multi-item scores (body image, sexual functioning, arm symptoms, breast symptoms, and systemic therapy side effects). Items are scored on a 4-point verbal rating scale: "Not at All," "A Little," "Quite a Bit," and "Very Much". Scores are transformed to a 0 to 100 scale, where higher scores indicate better unctioning, better HRQoL, or greater level of symptom
The EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 items) [ Time Frame: Up to Approximately 51 months ]
5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, pain, and nausea/vomiting), and global health status/QoL scale, along with 5 individual item symptom scores (appetite loss, dyspnoea, insomnia, constipation, and diarrhoea. The EORTC QLQ-C30 will be scored according to the EORTC QLQ-C30 Scoring Manual (Fayers et al. 2001). Higher scores on the global measure of health status and functional scales indicate better health status/function, but higher scores on symptom scales/scores represent greater symptom severity
Time to definitive deterioration of the ECOG (Eastern Cooperative Oncology Group) performance status [ Time Frame: Up to approximately 51 months ]
Time from randomisation to the earlier of the date of the first definitive deterioration or death due to any cause. Deterioration is defined as a 1-point decrease in ECOG score from baseline, and the deterioration is considered definitive if no improvements in the ECOG performance status are observed at a subsequent time of measurement during the treatment period, or at no further assessments following the time point where the deterioration is observed
Progression-Free Survival (PFS) in the overall population [ Time Frame: The time from date of randomisation to the date of progression or death due to any cause, whichever occurs earlier, up to approximately 51 months ]
Progression-Free Survival by investigator assessment (in accordance with RECIST 1.1)
Secondary Outcome Measures :
PFS in PIK3CA/AKT1/PTEN-altered subgroup [ Time Frame: The time from date of randomisation to the date of progression or death due to any cause, whichever occurs earlier, up to approximately 51 months ]
Progression-Free Survival by investigator assessment (in accordance with RECIST 1.1)
Overall Survival (OS) [ Time Frame: The time from date of randomisation to the date of death due to any cause up to 51 months ]
Overall Survival (OS)
Investigator assessment of PFS2 [ Time Frame: The time from the date of randomisation to the date of progression subsequent to the first subsequent therapy, or death due to any cause, whichever occurs earlier, up to approximately 51 months ]
PFS2 - time from randomisation to second progression by investigator assessment
Response Rate (ORR) [ Time Frame: Up to Approximately 51 months ]
percentage of patients with at least one investigator-assessed visit response of complete or partial response (as assessed by the investigator, using RECIST 1.1)
Duration of Response (DoR) [ Time Frame: Up to Approximately 51 months ]
time from the date of first documented response until date of documented progression (as assessed by the investigator, using RECIST 1.1) or death in the absence of disease progression
Clinical Benefit Rate (CBR) [ Time Frame: Up to Approximately 51 months ]
number of patients with complete or partial response or with stable disease maintained ≥24 weeks after randomisation (as assessed by the investigator, using RECIST 1.1)
ocurrence/frequency of AEs and its relationship to study drugs (safety and tolerability) [ Time Frame: Up to Approximately 51 months ]
AEs graded according to the National Cancer Institute (NCI CTCAE)
plasma concentration of capivasertib [ Time Frame: Minimum plasma concentration (Cmin), plasma concentration 1 hour post-dose (C1h) and 4 hours post-dose (C4h) during cycles 1 and 2 (each cycle is 28 days) ]
plasma concentration of capivasertib pre-dose and post-dose (C1h and C4h) in the overall population
EORTC QLQ BR23(European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire breast cancer specific module) [ Time Frame: Up to Approximately 51 months ]
The self-administered instrument includes 23-items and yields 5 multi-item scores (body image, sexual functioning, arm symptoms, breast symptoms, and systemic therapy side effects). Items are scored on a 4-point verbal rating scale: "Not at All," "A Little," "Quite a Bit," and "Very Much". Scores are transformed to a 0 to 100 scale, where higher scores indicate better unctioning, better HRQoL, or greater level of symptom
The EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 items) [ Time Frame: Up to Approximately 51 months ]
5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, pain, and nausea/vomiting), and global health status/QoL scale, along with 5 individual item symptom scores (appetite loss, dyspnoea, insomnia, constipation, and diarrhoea. The EORTC QLQ-C30 will be scored according to the EORTC QLQ-C30 Scoring Manual (Fayers et al. 2001). Higher scores on the global measure of health status and functional scales indicate better health status/function, but higher scores on symptom scales/scores represent greater symptom severity
Time to definitive deterioration of the ECOG (Eastern Cooperative Oncology Group) performance status [ Time Frame: Up to approximately 51 months ]
Time from randomisation to the earlier of the date of the first definitive deterioration or death due to any cause. Deterioration is defined as a 1-point decrease in ECOG score from baseline, and the deterioration is considered definitive if no improvements in the ECOG performance status are observed at a subsequent time of measurement during the treatment period, or at no further assessments following the time point where the deterioration is observed
Inclution Criteria
Inclusion Criteria:
Adult females, pre- and/or post-menopausal, and adult males. Pre-menopausal (and peri-menopausal) women can be enrolled if amenable to treatment with an LHRH agonist. Patients are to have commenced concomitant treatment with LHRH agonist at least 4 weeks prior to Cycle 1, Day 1 and must be willing to continue on it for the duration of the study
Histologically confirmed HR+/HER2- breast cancer determined from the most recent tumour sample (primary or metastatic), as per the American Society of Clinical Oncology and College of American Pathologists guideline recommendations. To fulfil the requirement of HR+ disease, a breast cancer must express ER with or without co-expression of progesterone receptor.
Metastatic or locally advanced disease with radiological or objective evidence of recurrence or progression; locally advanced disease must not be amenable to resection with curative intent (patients who are considered suitable for surgical or ablative techniques following potential down-staging with study treatment are not eligible)
ECOG/WHO PS: 0-1
Patients are to have received treatment with an AI containing regimen (single agent or in combination) and have:
Radiological evidence of breast cancer recurrence or progression while on, or within 12 months of the end of (neo)adjuvant treatment with an AI, OR
Radiological evidence of progression while on prior AI administered as a treatment line for locally advanced or metastatic breast cancer (this does not need to be the most recent therapy)
Patients must have measurable disease according to RECIST 1.1 and/or at least 1 lytic or mixed (lytic + sclerotic) bone lesion that can be assessed by CT or MRI; patients with sclerotic/osteoblastic bone lesions only in the absence of measurable disease are not eligible
FFPE tumour sample from primary/recurrent cancer for central testing
Adult females, pre- and/or post-menopausal, and adult males. Pre-menopausal (and peri-menopausal) women can be enrolled if amenable to treatment with an LHRH agonist. Patients are to have commenced concomitant treatment with LHRH agonist at least 4 weeks prior to Cycle 1, Day 1 and must be willing to continue on it for the duration of the study
Histologically confirmed HR+/HER2- breast cancer determined from the most recent tumour sample (primary or metastatic), as per the American Society of Clinical Oncology and College of American Pathologists guideline recommendations. To fulfil the requirement of HR+ disease, a breast cancer must express ER with or without co-expression of progesterone receptor.
Metastatic or locally advanced disease with radiological or objective evidence of recurrence or progression; locally advanced disease must not be amenable to resection with curative intent (patients who are considered suitable for surgical or ablative techniques following potential down-staging with study treatment are not eligible)
ECOG/WHO PS: 0-1
Patients are to have received treatment with an AI containing regimen (single agent or in combination) and have:
Radiological evidence of breast cancer recurrence or progression while on, or within 12 months of the end of (neo)adjuvant treatment with an AI, OR
Radiological evidence of progression while on prior AI administered as a treatment line for locally advanced or metastatic breast cancer (this does not need to be the most recent therapy)
Patients must have measurable disease according to RECIST 1.1 and/or at least 1 lytic or mixed (lytic + sclerotic) bone lesion that can be assessed by CT or MRI; patients with sclerotic/osteoblastic bone lesions only in the absence of measurable disease are not eligible
FFPE tumour sample from primary/recurrent cancer for central testing
Exclusion Criteria
Exclusion Criteria:
Symptomatic visceral disease or any disease burden that makes the patient ineligible for endocrine therapy per the investigator's best judgement
More than 2 lines of endocrine therapy for inoperable locally advanced or metastatic disease
More than 1 line of chemotherapy for inoperable locally advanced or metastatic disease. Adjuvant and neoadjuvant chemotherapy are not classed as lines of chemotherapy for advanced breast cancer
Prior treatment with any of the following:
AKT, PI3K and mTOR inhibitors
Fulvestrant, and other SERDs
Any other chemotherapy, immunotherapy, immunosuppressant medication (other than corticosteroids) or anticancer agents within 3 weeks prior to study treatment initiation.
Potent inhibitors or inducers of CYP3A4 within 2 weeks prior to the first dose of study treatment (3 weeks for St John's wort) or sensitive substrates of CYP3A4, CYP2C9 and/or CYP2D6 with a narrow therapeutic window within 1 week prior to study treatment initiation.
Radiotherapy with a wide field of radiation up to 4 weeks before study treatment initiation (capivasertib/placebo) and/or radiotherapy with a limited field of radiation for palliation up to 2 weeks before study treatment initiation (capivasertib/placebo)
With the exception of alopecia, any unresolved toxicities from prior therapy greater than CTCAE grade 1 at the time of starting study treatment
Spinal cord compression or brain metastases unless asymptomatic, treated and stable and not requiring steroids up to 4 weeks before study treatment initiation
Any of the following cardiac criteria:
Mean resting corrected QT interval (QTc) >470 msec obtained from 3 consecutive ECGs
Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (eg, complete left bundle branch block, third degree heart block)
Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, potential for torsades de pointes, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age or any concomitant medication known to prolong the QT interval
Experience of any of the following procedures or conditions in the preceding 6 months: coronary artery bypass graft, angioplasty, vascular stent, myocardial infarction, angina pectoris, congestive heart failure New York Heart Association (NYHA) grade ≥2
Uncontrolled hypotension - systolic blood pressure <90 mmHg and/or diastolic blood pressure <50 mmHg
Cardiac ejection fraction outside institutional range of normal or <50% (whichever is higher) as measured by echocardiogram (or multiple-gated acquisition [MUGA] scan if an echocardiogram cannot be performed or is inconclusive)
Clinically significant abnormalities of glucose metabolism as defined by any of the following:
Patients with diabetes mellitus type 1 or diabetes mellitus type 2 requiring insulin treatment
HbA1c ≥8.0% (63.9 mmol/mol)
Known abnormalities in coagulation such as bleeding diathesis, or treatment with anticoagulants precluding intramuscular injections of fulvestrant or LHRH (if applicable)
Currently pregnant (confirmed with positive pregnancy test) or breast-feeding
Symptomatic visceral disease or any disease burden that makes the patient ineligible for endocrine therapy per the investigator's best judgement
More than 2 lines of endocrine therapy for inoperable locally advanced or metastatic disease
More than 1 line of chemotherapy for inoperable locally advanced or metastatic disease. Adjuvant and neoadjuvant chemotherapy are not classed as lines of chemotherapy for advanced breast cancer
Prior treatment with any of the following:
AKT, PI3K and mTOR inhibitors
Fulvestrant, and other SERDs
Any other chemotherapy, immunotherapy, immunosuppressant medication (other than corticosteroids) or anticancer agents within 3 weeks prior to study treatment initiation.
Potent inhibitors or inducers of CYP3A4 within 2 weeks prior to the first dose of study treatment (3 weeks for St John's wort) or sensitive substrates of CYP3A4, CYP2C9 and/or CYP2D6 with a narrow therapeutic window within 1 week prior to study treatment initiation.
Radiotherapy with a wide field of radiation up to 4 weeks before study treatment initiation (capivasertib/placebo) and/or radiotherapy with a limited field of radiation for palliation up to 2 weeks before study treatment initiation (capivasertib/placebo)
With the exception of alopecia, any unresolved toxicities from prior therapy greater than CTCAE grade 1 at the time of starting study treatment
Spinal cord compression or brain metastases unless asymptomatic, treated and stable and not requiring steroids up to 4 weeks before study treatment initiation
Any of the following cardiac criteria:
Mean resting corrected QT interval (QTc) >470 msec obtained from 3 consecutive ECGs
Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (eg, complete left bundle branch block, third degree heart block)
Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, potential for torsades de pointes, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age or any concomitant medication known to prolong the QT interval
Experience of any of the following procedures or conditions in the preceding 6 months: coronary artery bypass graft, angioplasty, vascular stent, myocardial infarction, angina pectoris, congestive heart failure New York Heart Association (NYHA) grade ≥2
Uncontrolled hypotension - systolic blood pressure <90 mmHg and/or diastolic blood pressure <50 mmHg
Cardiac ejection fraction outside institutional range of normal or <50% (whichever is higher) as measured by echocardiogram (or multiple-gated acquisition [MUGA] scan if an echocardiogram cannot be performed or is inconclusive)
Clinically significant abnormalities of glucose metabolism as defined by any of the following:
Patients with diabetes mellitus type 1 or diabetes mellitus type 2 requiring insulin treatment
HbA1c ≥8.0% (63.9 mmol/mol)
Known abnormalities in coagulation such as bleeding diathesis, or treatment with anticoagulants precluding intramuscular injections of fulvestrant or LHRH (if applicable)
Currently pregnant (confirmed with positive pregnancy test) or breast-feeding
The Estimated Number of Participants
-
Taiwan
27 participants
-
Global
700 participants
