Clinical Trials List
Protocol NumberCBKM120F2302
2012-09-01 - 2018-12-18
Phase III
Terminated5
A phase III randomized, double blind placebo controlled study of oral BKM120 in combination with fulvestrant, in the treatment of postmenopausal women with hormone receptor-positive HER2-negative locally advanced or metastatic breast cancer whose disease has progressed on or after aromatase inhibitor treatment
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Trial Applicant
NOVARTIS (TAIWAN) CO., LTD.
-
Sponsor
Novartis
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- 陳怡君 Division of Hematology & Oncology
- Wei-Wu Chen Division of Hematology & Oncology
- 張端瑩 Division of Hematology & Oncology
- 林璟宏 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Yi-Fang Tsai Division of General Surgery
- 金光亮 Division of General Surgery
- Ta-Chung Chao Division of Hematology & Oncology
- 賴亦貞 Division of Radiology
- Chun-Yu Liu Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Chieh-Han Chuang Division of General Surgery
- Fang-Ming Chen Division of General Surgery
- Fu Ouyang Division of General Surgery
- Jui-Sheng Hsu Division of General Surgery
The Actual Total Number of Participants Enrolled
0 Stop recruiting
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- 蔡伯邦 Division of General Surgery
- Chih-Jung Chen Division of General Surgery
- Liang-Chih Liu Division of General Surgery
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Condition/Disease
locally advanced or metastatic breast cancer
Objectives
A phase III randomized, double blind placebo controlled study of oral BKM120 in combination with fulvestrant, in the treatment of postmenopausal women with hormone receptor-positive HER2-negative locally advanced or metastatic breast cancer whose disease has progressed on or after aromatase inhibitor treatment
Test Drug
BKM120
Active Ingredient
BKM120
Dosage Form
capsule
Dosage
10
50
50
Endpoints
A phase III randomized, double blind placebo controlled study of oral BKM120 in combination with
fulvestrant, in the treatment of postmenopausal women with hormone receptor-positive HER2-negative
locally advanced or metastatic breast cancer whose disease has progressed on or after aromatase
inhibitor treatment
fulvestrant, in the treatment of postmenopausal women with hormone receptor-positive HER2-negative
locally advanced or metastatic breast cancer whose disease has progressed on or after aromatase
inhibitor treatment
Inclution Criteria
Patients eligible for inclusion in this study have to meet all of the following criteria:
1. Patient is an adult, female ≥ 18 years old at the time of informed consent
2. Patient has histologically and/or cytologically confirmed diagnosis of breast cancer
3. Patient has archival tumor tissue for the analysis of PI3K-related biomarkers (PIK3CA
mutation, PTEN mutation, PTEN expression). One tumor block (preferred) or a minimum
of 20 unstained slides is recommended to determine the PI3K activation status.
Enrollment in the study will be contingent to the central laboratory confirming reception
of adequate amount of tissue
4. Patient has inoperable locally advanced or metastatic breast cancer
5. Patient has HER2 negative breast cancer (based on most recently analyzed biopsy) defined
as a negative immunohistochemistry, fluorescent, non-florescent chromogenic or silver in
situ hybridization (respectively FISH/CISH/SISH) test or an IHC status of 0, 1+ or 2+ (if IHC 2+, a negative SISH/FISH/CISH test is required) by local laboratory testing
6. Patient has ER positive and/or PgR positive breast cancer by local laboratory testing
7. Patient is postmenopausal. Women are considered post-menopausal and not of child
bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an
appropriate clinical profile (e.g., age appropriate, history of vasomotor symptoms) or six
months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL and estradiol <
20 pg/mL or have had surgical bilateral oophorectomy (with or without hysterectomy) at
least six weeks ago. In the case of oophorectomy alone, only when the reproductive status
of the woman has been confirmed by follow up hormone level assessment is she
considered not of child bearing potential
8. Patient has disease refractory to AI defined as:
• Recurrence while on, or within 12 months of end of adjuvant treatment with AI, or
• Progression while on, or within one month of end of AI treatment for locally
advanced or MBC
Note: AI do not have to be the last treatment prior to enrollment in the run-in treatment
phase. Patients who received maximum one prior chemotherapy line for MBC are
allowed. Other prior anticancer therapies, e.g. tamoxifen are also allowed. Patients do
not need to meet the definition of “refractory to AI” within any specified time period
prior to enrollment in the run-in treatment phase. Patients can receive any number of
endocrine/hormonal lines of therapy before or after meeting the definition of
“refractory to AI”
9. Patient is able to swallow and retain oral medication
10. Radiological or objective evidence of recurrence or progression on or after the last
systemic therapy prior to enrollment in the run-in treatment phase.
11. Patient must have as per RECIST 1.1 (Appendix 7):
• measurable disease
or
• non-measurable lytic or mixed (lytic + blastic) bone lesions in the absence of
measurable disease.
Note: Measurable lesions include lytic or mixed (lytic + blastic) bone lesions, with an
identifiable soft tissue component that meets the measurability criteria per RECIST
1.1. Patients with only non-measurable lesions (e.g. pleural effusion, ascites) and no
lytic or a mix of lytic and blastic bone lesions are not eligible.
12. Patient has adequate bone marrow and organ function as defined by the following
laboratory values:
• Absolute Neutrophil Count (ANC) ≥ 1.0 x 109/L
• Platelets (plt) ≥ 100 x 109/L
• Hemoglobin (Hgb) ≥ 9 g/dl
• INR ≤ 1.5
• Potassium, calcium (corrected for serum albumin) and magnesium within normal
limits (WNL) for the institution
• Serum creatinine ≤ 1.5 x ULN
• Alanine aminotransferase (AST) and aspartate aminotransferase (ALT) within normal
range (or < 3.0 x ULN if liver metastases are present)
• Total serum bilirubin within normal range (or ≤ 1.5 x ULN if liver metastases are
present; or total bilirubin ≤ 3.0 x ULN with direct bilirubin within normal range in
patients with well documented Gilbert’s Syndrome, which is defined as presence of
several episodes of unconjugated hyperbilirubinemia with normal results from CBC
count (including normal reticulocyte count and blood smear), normal liver function
test results, and absence of other contributing disease processes at the time of
diagnosis (see Appendix 1)
• Fasting plasma glucose ≤ 120 mg/dL or 6.7 mmol/L
• HbA1c ≤ 8 %
13. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 which the investigator believes is stable at the time of screening
14. Patient has signed informed consents obtained before any trial related activities and according to local guidelines
1. Patient is an adult, female ≥ 18 years old at the time of informed consent
2. Patient has histologically and/or cytologically confirmed diagnosis of breast cancer
3. Patient has archival tumor tissue for the analysis of PI3K-related biomarkers (PIK3CA
mutation, PTEN mutation, PTEN expression). One tumor block (preferred) or a minimum
of 20 unstained slides is recommended to determine the PI3K activation status.
Enrollment in the study will be contingent to the central laboratory confirming reception
of adequate amount of tissue
4. Patient has inoperable locally advanced or metastatic breast cancer
5. Patient has HER2 negative breast cancer (based on most recently analyzed biopsy) defined
as a negative immunohistochemistry, fluorescent, non-florescent chromogenic or silver in
situ hybridization (respectively FISH/CISH/SISH) test or an IHC status of 0, 1+ or 2+ (if IHC 2+, a negative SISH/FISH/CISH test is required) by local laboratory testing
6. Patient has ER positive and/or PgR positive breast cancer by local laboratory testing
7. Patient is postmenopausal. Women are considered post-menopausal and not of child
bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an
appropriate clinical profile (e.g., age appropriate, history of vasomotor symptoms) or six
months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL and estradiol <
20 pg/mL or have had surgical bilateral oophorectomy (with or without hysterectomy) at
least six weeks ago. In the case of oophorectomy alone, only when the reproductive status
of the woman has been confirmed by follow up hormone level assessment is she
considered not of child bearing potential
8. Patient has disease refractory to AI defined as:
• Recurrence while on, or within 12 months of end of adjuvant treatment with AI, or
• Progression while on, or within one month of end of AI treatment for locally
advanced or MBC
Note: AI do not have to be the last treatment prior to enrollment in the run-in treatment
phase. Patients who received maximum one prior chemotherapy line for MBC are
allowed. Other prior anticancer therapies, e.g. tamoxifen are also allowed. Patients do
not need to meet the definition of “refractory to AI” within any specified time period
prior to enrollment in the run-in treatment phase. Patients can receive any number of
endocrine/hormonal lines of therapy before or after meeting the definition of
“refractory to AI”
9. Patient is able to swallow and retain oral medication
10. Radiological or objective evidence of recurrence or progression on or after the last
systemic therapy prior to enrollment in the run-in treatment phase.
11. Patient must have as per RECIST 1.1 (Appendix 7):
• measurable disease
or
• non-measurable lytic or mixed (lytic + blastic) bone lesions in the absence of
measurable disease.
Note: Measurable lesions include lytic or mixed (lytic + blastic) bone lesions, with an
identifiable soft tissue component that meets the measurability criteria per RECIST
1.1. Patients with only non-measurable lesions (e.g. pleural effusion, ascites) and no
lytic or a mix of lytic and blastic bone lesions are not eligible.
12. Patient has adequate bone marrow and organ function as defined by the following
laboratory values:
• Absolute Neutrophil Count (ANC) ≥ 1.0 x 109/L
• Platelets (plt) ≥ 100 x 109/L
• Hemoglobin (Hgb) ≥ 9 g/dl
• INR ≤ 1.5
• Potassium, calcium (corrected for serum albumin) and magnesium within normal
limits (WNL) for the institution
• Serum creatinine ≤ 1.5 x ULN
• Alanine aminotransferase (AST) and aspartate aminotransferase (ALT) within normal
range (or < 3.0 x ULN if liver metastases are present)
• Total serum bilirubin within normal range (or ≤ 1.5 x ULN if liver metastases are
present; or total bilirubin ≤ 3.0 x ULN with direct bilirubin within normal range in
patients with well documented Gilbert’s Syndrome, which is defined as presence of
several episodes of unconjugated hyperbilirubinemia with normal results from CBC
count (including normal reticulocyte count and blood smear), normal liver function
test results, and absence of other contributing disease processes at the time of
diagnosis (see Appendix 1)
• Fasting plasma glucose ≤ 120 mg/dL or 6.7 mmol/L
• HbA1c ≤ 8 %
13. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 which the investigator believes is stable at the time of screening
14. Patient has signed informed consents obtained before any trial related activities and according to local guidelines
Exclusion Criteria
1. Patient has received previous treatment with PI3K inhibitors, AKT inhibitors, mTORi or
fulvestrant
2. Patient has received more than one chemotherapy line for metastatic disease
• A chemotherapy line in advanced disease is an anticancer regimen(s) that contains at
least 1 cytotoxic chemotherapy agent and was discontinued due to progression. If a
cytotoxic chemotherapy regimen was discontinued for a reason other than disease
progression then this regimen does not count as a "prior line of chemotherapy"
• Adjuvant/neo-adjuvant therapy will be counted as prior line of chemotherapy for
metastatic/recurrent disease if the patient had a progression/recurrence while or within
6 months after completion of the therapy (12 months for taxane-based therapy)
3. Patient has a known hypersensitivity to any of the excipients of BKM120 or fulvestrant
4. Patient has symptomatic CNS metastases
• Patients with asymptomatic CNS metastases may participate in this trial. The patient
must have completed any prior local treatment for CNS metastases ≥ 28 days prior to
the entry in the run-in treatment phase (including radiotherapy and/or surgery)
5. Patient has a concurrent malignancy or malignancy within 3 years of study enrollment
(with the exception of adequately treated, basal or squamous cell carcinoma, nonmelanomatous skin cancer or curatively resected cervical cancer).
6. Patient who has received wide field radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to starting study drug or who have not recovered to grade 1 or better from related side effects of such therapy (exceptions include alopecia, bone marrow and organ functions)
7. Patient has not recovered to grade 1 or better (except alopecia) from related side effects of any prior antineoplastic therapy
8. Patient has had major surgery within 14 days prior to starting study drug or has not
recovered from major side effects
9. Patient is currently receiving increasing or chronic treatment (> 5 days) with
corticosteroids or another immunosuppressive agent, as chronic administration of
corticosteroids (> 5 days) can induce CYP3A4
• The following uses of corticosteroids are permitted: single doses; topical applications
(e.g., rash), inhaled sprays (e.g., obstructive airways diseases), eye drops or local
injections (e.g., intra-articular)
10. Patient is currently receiving warfarin or other coumarin derived anti-coagulant, for
treatment, prophylaxis or otherwise. Therapy with heparin, low molecular weight heparin
(LMWH), or fondaparinux is allowed
11. Patient is currently receiving treatment with drugs known to be moderate or strong
inhibitors or inducers of isoenzyme CYP3A. The patient must have discontinued strong
inducers for at least one week and must have discontinued strong inhibitors before the runin
treatment phase is initiated. Switching to a different medication prior to entry in the
run-in treatment phase is allowed. Please refer to the Table 14-1 in Appendix 2 for a list of
strong and moderate inhibitors and inducers of CYP3A4
12. Patient has a score ≥ 12 on the PHQ-9 questionnaire
13. Patient selects a response of “1, 2 or 3” to question number 9 on the PHQ-9 questionnaire
regarding potential for suicidal thoughts or ideation (independent of the total score of the
PHQ-9)
14. Patient has a GAD-7 mood scale score ≥ 15
15. Patient has a medically documented history of or active major depressive episode, bipolar
disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal
attempt or ideation, or homicidal ideation (e.g. risk of doing harm to self or others)
16. Patient has ≥ CTCAE grade 3 anxiety
17. Patient has active cardiac disease or a history of cardiac dysfunction including any of the
following:
a. Unstable angina pectoris within 6 months prior to study entry
b. Symptomatic pericarditis
c. Documented myocardial infarction within 6 months prior to study entry
d. History of documented congestive heart failure (New York Heart Association
functional classification III-IV)
e. Documented cardiomyopathy
18. Patient has a Left Ventricular Ejection Fraction (LVEF) < 50% as determined by Multiple
Gated acquisition (MUGA) scan or echocardiogram (ECHO)
19. Patient has any of the following cardiac conduction abnormalities
a. Ventricular arrhythmias except for benign premature ventricular contractions
b. Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication
c. Conduction abnormality requiring a pacemaker
d. Other cardiac arrhythmia not controlled with medication
e. Patient has a QTcF > 480 msec on the screening ECG (using the QTcF formula)
20. Patient is currently receiving treatment with medication that has a known risk to prolong
the QT interval or inducing Torsades de Pointes, and the treatment cannot be discontinued
or switched to a different medication prior to randomization. Please refer to Table 14-3 in
Appendix 4 for a list of prohibited drugs
21. Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of BKM120 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
22. Patient has any other concurrent severe and/or uncontrolled medical condition that would, in the investigator’s judgment contraindicate patient participation in the clinical study (e.g.
chronic pancreatitis, chronic active hepatitis, etc.)
23. Patient has a history of non-compliance to medical regimen or inability to grant consent
24. Patient has a known history of HIV infection (testing not mandatory) infection
25. Patient is concurrently using other approved or investigational antineoplastic agent.
fulvestrant
2. Patient has received more than one chemotherapy line for metastatic disease
• A chemotherapy line in advanced disease is an anticancer regimen(s) that contains at
least 1 cytotoxic chemotherapy agent and was discontinued due to progression. If a
cytotoxic chemotherapy regimen was discontinued for a reason other than disease
progression then this regimen does not count as a "prior line of chemotherapy"
• Adjuvant/neo-adjuvant therapy will be counted as prior line of chemotherapy for
metastatic/recurrent disease if the patient had a progression/recurrence while or within
6 months after completion of the therapy (12 months for taxane-based therapy)
3. Patient has a known hypersensitivity to any of the excipients of BKM120 or fulvestrant
4. Patient has symptomatic CNS metastases
• Patients with asymptomatic CNS metastases may participate in this trial. The patient
must have completed any prior local treatment for CNS metastases ≥ 28 days prior to
the entry in the run-in treatment phase (including radiotherapy and/or surgery)
5. Patient has a concurrent malignancy or malignancy within 3 years of study enrollment
(with the exception of adequately treated, basal or squamous cell carcinoma, nonmelanomatous skin cancer or curatively resected cervical cancer).
6. Patient who has received wide field radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to starting study drug or who have not recovered to grade 1 or better from related side effects of such therapy (exceptions include alopecia, bone marrow and organ functions)
7. Patient has not recovered to grade 1 or better (except alopecia) from related side effects of any prior antineoplastic therapy
8. Patient has had major surgery within 14 days prior to starting study drug or has not
recovered from major side effects
9. Patient is currently receiving increasing or chronic treatment (> 5 days) with
corticosteroids or another immunosuppressive agent, as chronic administration of
corticosteroids (> 5 days) can induce CYP3A4
• The following uses of corticosteroids are permitted: single doses; topical applications
(e.g., rash), inhaled sprays (e.g., obstructive airways diseases), eye drops or local
injections (e.g., intra-articular)
10. Patient is currently receiving warfarin or other coumarin derived anti-coagulant, for
treatment, prophylaxis or otherwise. Therapy with heparin, low molecular weight heparin
(LMWH), or fondaparinux is allowed
11. Patient is currently receiving treatment with drugs known to be moderate or strong
inhibitors or inducers of isoenzyme CYP3A. The patient must have discontinued strong
inducers for at least one week and must have discontinued strong inhibitors before the runin
treatment phase is initiated. Switching to a different medication prior to entry in the
run-in treatment phase is allowed. Please refer to the Table 14-1 in Appendix 2 for a list of
strong and moderate inhibitors and inducers of CYP3A4
12. Patient has a score ≥ 12 on the PHQ-9 questionnaire
13. Patient selects a response of “1, 2 or 3” to question number 9 on the PHQ-9 questionnaire
regarding potential for suicidal thoughts or ideation (independent of the total score of the
PHQ-9)
14. Patient has a GAD-7 mood scale score ≥ 15
15. Patient has a medically documented history of or active major depressive episode, bipolar
disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal
attempt or ideation, or homicidal ideation (e.g. risk of doing harm to self or others)
16. Patient has ≥ CTCAE grade 3 anxiety
17. Patient has active cardiac disease or a history of cardiac dysfunction including any of the
following:
a. Unstable angina pectoris within 6 months prior to study entry
b. Symptomatic pericarditis
c. Documented myocardial infarction within 6 months prior to study entry
d. History of documented congestive heart failure (New York Heart Association
functional classification III-IV)
e. Documented cardiomyopathy
18. Patient has a Left Ventricular Ejection Fraction (LVEF) < 50% as determined by Multiple
Gated acquisition (MUGA) scan or echocardiogram (ECHO)
19. Patient has any of the following cardiac conduction abnormalities
a. Ventricular arrhythmias except for benign premature ventricular contractions
b. Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication
c. Conduction abnormality requiring a pacemaker
d. Other cardiac arrhythmia not controlled with medication
e. Patient has a QTcF > 480 msec on the screening ECG (using the QTcF formula)
20. Patient is currently receiving treatment with medication that has a known risk to prolong
the QT interval or inducing Torsades de Pointes, and the treatment cannot be discontinued
or switched to a different medication prior to randomization. Please refer to Table 14-3 in
Appendix 4 for a list of prohibited drugs
21. Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of BKM120 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
22. Patient has any other concurrent severe and/or uncontrolled medical condition that would, in the investigator’s judgment contraindicate patient participation in the clinical study (e.g.
chronic pancreatitis, chronic active hepatitis, etc.)
23. Patient has a history of non-compliance to medical regimen or inability to grant consent
24. Patient has a known history of HIV infection (testing not mandatory) infection
25. Patient is concurrently using other approved or investigational antineoplastic agent.
The Estimated Number of Participants
-
Taiwan
30 participants
-
Global
842 participants
