Clinical Trials List
Protocol NumberCO40016
NCT Number(ClinicalTrials.gov Identfier)NCT03337724
2017-12-01 - 2021-12-31
Phase III
Terminated3
ICD-10C50
Malignant neoplasm of breast
A Double-Blind, Placebo-Controlled, Randomized Phase III Study of Ipatasertib in Combination With Paclitaxel as a Treatment for Patients With PIK3CA/AKT1/PTEN-Altered, Locally Advanced or Metastatic, Triple-Negative Breast Cancer or Hormone Receptor-Positive, HER2-Negative Breast Cancer
-
Trial Applicant
-
Sponsor
Hoffmann-La Roche
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- 邱仁輝 Division of General Surgery
- 賴亦貞 Division of Radiology
- Yi-Fang Tsai Division of General Surgery
- Chun-Yu Liu Division of Hematology & Oncology
- Ta-Chung Chao Division of Hematology & Oncology
- 林燕淑 Division of General Surgery
The Actual Total Number of Participants Enrolled
6 Terminated
Audit
None
Co-Principal Investigator
- 褚乃銘 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 郭文宏 Division of General Surgery
- 蔡立威 Division of General Surgery
- 林柏翰 Division of General Internal Medicine
- SUNG-HSIN KUO Division of Hematology & Oncology
- Wei-Wu Chen Division of Hematology & Oncology
- 羅喬 Division of General Surgery
- 張端瑩 Division of Hematology & Oncology
- MING-YANG WANG Division of General Surgery
- YEN-SHEN LU Division of Hematology & Oncology
- 林季宏 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Audit
None
Condition/Disease
TNBC, HR+/HER2- breast cancer
Objectives
This study will evaluate the efficacy of ipatasertib + paclitaxel versus placebo + paclitaxel in participants with histologically confirmed, locally advanced or metastatic triple-negative breast cancer (TNBC) and in participants with locally advanced or metastatic hormone receptor positive (HR+)/ human epidermal growth factor receptor 2 negative (HER2-) breast adenocarcinoma who are not suitable for endocrine therapy.
Test Drug
IPATASERTIB
Active Ingredient
IPATASERTIB
Dosage Form
tablet
Dosage
100mg / 200mg
Endpoints
This protocol encompasses two studies, or cohorts, of different patient populations that
will independently evaluate the safety, efficacy, and pharmacokinetics of ipatasertib in
combination with paclitaxel (ipatasertib + paclitaxel) compared with placebo plus
paclitaxel (placebo + paclitaxel) in patients with PIK3CA/AKT1/PTEN-altered tumors.
One cohort will be a first-line treatment in patients with locally advanced or metastatic
TNBC and the second will be a first-chemotherapy treatment in patients with advanced
HR+/HER2− breast cancer who are not appropriate candidates for endocrine therapy.
Patients will be screened for PIK3CA/AKT1/PTEN-altered tumors for eligibility and will
be allocated to one of the cohorts based on hormone-receptor status. HER2-positive
patients are not eligible. The reason that the two patient populations will be evaluated
separately is that TNBC and HR+/HER2− breast cancers have different biologies that
manifest clinically in different prognoses and response to treatment, and molecularly with
distinctly different molecular profiles with dissimilar oncogenic drivers. The two
populations have different prevalences and PFS and OS expectations, and thus different
enrollment and analysis timelines.
The two independent target patient populations for this study are premenopausal and
postmenopausal female and male patients with measurable, locally advanced or
metastatic TNBC and HR+/HER2− breast cancer who have not received chemotherapy
for advanced disease. Patients must be appropriate candidates for taxane
chemotherapy. In particular, patients with HR+/HER2− breast cancer should be suitable
for treatment with chemotherapy (e.g., experiencing symptomatic visceral disease or
demonstrated insensitivity to endocrine therapy). Prior adjuvant or neoadjuvant
chemotherapy is allowed, provided it has been concluded for at least 12 months before
randomization.
Patients with PIK3CA/AKT1/PTEN-altered tumors (as defined in Section 3.1.1 and
Section 4.1.1) will be assigned to Cohort A (TNBC) or Cohort B (HR+/HER2− breast
cancer) based on their hormone receptor status (as evaluated locally; via central
laboratory only if local evaluation is not available, with additional slides submitted for this
purpose) and randomized with a 2:1 ratio to the experimental versus control arm. All
primary, secondary, exploratory, and safety objectives will be assessed independently
for each cohort (i.e., Cohort A: patients with TNBC with PIK3CA/AKT1/PTEN-altered
tumors and Cohort B: patients with HR+/HER2− breast cancer with
PIK3CA/AKT1/PTEN-altered tumors).
The primary endpoint for the Cohort A (TNBC) is PFS. The primary endpoint for Cohort
B (HR+/HER2− breast cancer) is also PFS. The primary analysis for each cohort will be
independent and triggered by cohort-specific events and will also be independent of the
readout of the other cohort (refer to Section 6). The secondary endpoints for each
cohort will be tested if the primary analysis of the respective PFS reaches statistical
significance at the level of 5%.
will independently evaluate the safety, efficacy, and pharmacokinetics of ipatasertib in
combination with paclitaxel (ipatasertib + paclitaxel) compared with placebo plus
paclitaxel (placebo + paclitaxel) in patients with PIK3CA/AKT1/PTEN-altered tumors.
One cohort will be a first-line treatment in patients with locally advanced or metastatic
TNBC and the second will be a first-chemotherapy treatment in patients with advanced
HR+/HER2− breast cancer who are not appropriate candidates for endocrine therapy.
Patients will be screened for PIK3CA/AKT1/PTEN-altered tumors for eligibility and will
be allocated to one of the cohorts based on hormone-receptor status. HER2-positive
patients are not eligible. The reason that the two patient populations will be evaluated
separately is that TNBC and HR+/HER2− breast cancers have different biologies that
manifest clinically in different prognoses and response to treatment, and molecularly with
distinctly different molecular profiles with dissimilar oncogenic drivers. The two
populations have different prevalences and PFS and OS expectations, and thus different
enrollment and analysis timelines.
The two independent target patient populations for this study are premenopausal and
postmenopausal female and male patients with measurable, locally advanced or
metastatic TNBC and HR+/HER2− breast cancer who have not received chemotherapy
for advanced disease. Patients must be appropriate candidates for taxane
chemotherapy. In particular, patients with HR+/HER2− breast cancer should be suitable
for treatment with chemotherapy (e.g., experiencing symptomatic visceral disease or
demonstrated insensitivity to endocrine therapy). Prior adjuvant or neoadjuvant
chemotherapy is allowed, provided it has been concluded for at least 12 months before
randomization.
Patients with PIK3CA/AKT1/PTEN-altered tumors (as defined in Section 3.1.1 and
Section 4.1.1) will be assigned to Cohort A (TNBC) or Cohort B (HR+/HER2− breast
cancer) based on their hormone receptor status (as evaluated locally; via central
laboratory only if local evaluation is not available, with additional slides submitted for this
purpose) and randomized with a 2:1 ratio to the experimental versus control arm. All
primary, secondary, exploratory, and safety objectives will be assessed independently
for each cohort (i.e., Cohort A: patients with TNBC with PIK3CA/AKT1/PTEN-altered
tumors and Cohort B: patients with HR+/HER2− breast cancer with
PIK3CA/AKT1/PTEN-altered tumors).
The primary endpoint for the Cohort A (TNBC) is PFS. The primary endpoint for Cohort
B (HR+/HER2− breast cancer) is also PFS. The primary analysis for each cohort will be
independent and triggered by cohort-specific events and will also be independent of the
readout of the other cohort (refer to Section 6). The secondary endpoints for each
cohort will be tested if the primary analysis of the respective PFS reaches statistical
significance at the level of 5%.
Inclution Criteria
General Inclusion Criteria
Patients must meet the following general criteria for study entry:
• Signed Informed Consent Form(s)
• Woman or man age≥ 18 years at the time of signing the Informed Consent Form
• Eastern Cooperative Oncology Group Performance Status of 0 or 1
• Adequate hematologic and organ function within 14 days before the first study
treatment on Day 1 of Cycle 1, defined by the following:
– Neutrophils (ANC ≥ 1500/µL)
– Hemoglobin ≥ 9 g/dL
– Platelet count ≥ 100,000/µL
– Serum albumin ≥ 3 g/dL
– Total bilirubin ≤ 1.5 × the upper limit of normal (ULN), with the following
exception:
Patients with known Gilbert syndrome who have serum bilirubin ≤ 3×ULN
may be enrolled.
– AST and ALT ≤ 2.5× ULN, with the following exception:
Patients with documented liver or bone metastases may have AST and
ALT ≤ 5×ULN.
– ALP ≤ 2× ULN, with the following exceptions:
Patients with known liver involvement may have ALP ≤ 5× ULN
Patients with known bone involvement may have ALP ≤ 7× ULN
– PTT (or aPTT) and INR ≤ 1.5 ×ULN (except for patients receiving
anticoagulation therapy)
Patients receiving heparin treatment should have a PTT (or aPTT)
between 1.5 and 2.5× ULN (or patient value before starting heparin
treatment). Patients receiving coumarin derivatives should have an INR
between 2.0 and 3.0 assessed in two consecutive measurements 1 to
4 days apart.
– Serum creatinine < 1.5 × ULN or creatinine clearance ≥50 mL/min based on
Cockcroft−Gault glomerular filtration rate estimation:
– Fasting total serum glucose ≤150 mg/dL and HbA1C ≤ 7.5%
• Life expectancy of at least 6 months
• For women of childbearing potential: agreement to remain abstinent (refrain from
heterosexual intercourse) or use contraceptive methods with a failure rate of <1%
per year during the treatment period and for at least 28 days after the last dose of
ipatasertib/placebo and 6 months after the last dose of paclitaxel, whichever occurs
later
– A woman is considered to be of childbearing potential if she is
postmenarcheal, has not reached a postmenopausal state (≥12 continuous
months of amenorrhea with no identified cause other than menopause),
and has not undergone surgical sterilization (removal of ovaries and/or
uterus).
– Examples of contraceptive methods with a failure rate of < 1% per year,
when used consistently and correctly, include combined (estrogen and
progestogen containing) hormonal contraception associated with inhibition
of ovulation, progestogen-only hormonal contraception associated with
inhibition of ovulation, bilateral tubal occlusion, male sterilization,
intrauterine hormone-releasing system, and sexual abstinence.
– Hormonal contraceptive methods may be used in accordance with specific
country and local requirements for patients with breast cancer.
– The reliability of sexual abstinence should be evaluated in relation to the
duration of the clinical trial and the preferred and usual lifestyle of the
patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or
postovulation methods) and withdrawal are not acceptable methods of
contraception.
• For men: agreement to remain abstinent (refrain from heterosexual intercourse) or
use contraceptive measures, and agreement to refrain from donating sperm, as
defined below:
– With female partners of childbearing potential, men must remain abstinent
or use a condom plus an additional contraceptive method that together
result in a failure rate of < 1% per year during the treatment period and for
28 days after the last dose of ipatasertib or 6 months after the last dose of
paclitaxel, whichever occurs later. Men must refrain from donating sperm
during this same period.
– With pregnant female partners, men must remain abstinent or use a
condom during the treatment period and for 28 days after the last dose of
ipatasertib or 6 months after the last dose of paclitaxel, whichever occurs
later, to avoid exposing the embryo.
– Examples of contraceptive methods with a failure rate of < 1% per year,
when used consistently and correctly, include combined (estrogen and
progestogen containing) hormonal contraception associated with inhibition
of ovulation, progestogen-only hormonal contraception associated with
inhibition of ovulation, bilateral tubal occlusion, male sterilization,
intrauterine hormone-releasing system, and sexual abstinence.
– The reliability of sexual abstinence should be evaluated in relation to the
duration of the clinical trial and the preferred and usual lifestyle of the
patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or
postovulation methods) and withdrawal are not acceptable methods of
contraception.
Disease-Specific Inclusion Criteria
Patients must meet the following disease-specific criteria for study entry:
• Histologically documented TNBC or HR+/HER2– adenocarcinoma of the breast that
is locally advanced or metastatic and is not amenable to resection with curative
intent
– Receptor status at study entry should correspond to the evaluation of the
most recent biopsy (non−fine-needle aspiration [FNA] sample), as
assessed locally (or centrally, if not available locally) according to the
ASCO/CAP guidelines (see Appendix 3 and Appendix 4):
HER2+ is defined as one of the following: immunohistochemistry 3+ or
in situ hybridization positive
ER or PgR positivity is defined as ≥ 1% of tumor cell nuclei immunoreactive
to the respective hormonal receptor
TNBC is defined as HER2–, ER–, and PgR– (required for eligibility for
Cohort A)
HR+/HER2– is defined as HER2– and ER+ and/or PgR+ (required for
eligibility for Cohort B)
• Measurable disease according to RECIST v1.1
• Submission of a formalin-fixed, paraffin-embedded tumor (FFPE) tissue block or a
minimum of 20 freshly cut unstained, serial tumor slides from the most recently
collected tumor tissue for central molecular analysis (mandatory NGS testing for
eligibility [PIK3CA/AKT1/PTEN-altered status] and for other protocol-mandated
secondary and exploratory assessments). Cytologic or FNA samples are not
acceptable. Tumor tissue from bone metastases that is subject to decalcification is
not acceptable.
– If the specimen is either insufficient or unavailable, the patient may still be
eligible if the patient can provide a tissue block (preferred) or a minimum of
20 unstained serial slides from an older archival tumor tissue or is willing to
consent to and undergo an additional pretreatment core or excisional
biopsy of the non-target lesion (if it is assessable and the biopsy can be
safely obtained). In general, a minimum of three core biopsies for NGS
testing are required.
• Valid results confirming PIK3CA/AKT1/PTEN-altered status in tumor tissue, defined
as the presence of one or more of the following by NGS:
– AKT1 missense mutations that result in amino acid substitution at the
following residues E17, L52, or Q79
– PIK3CA missense mutations that result in amino acid substitution at the
following residues R88, G106, K111, G118, N345, C420, E453, E542,
E545, Q546, M1043, H1047, or G1049
– PTEN alterations that meet any of the following criteria:
Homozygous deletion (copy number of 0)
Dominant negative short variant (e.g., C124S, G129E, R130X;
Papa et al. 2014)
Loss of heterozygosity (LOH) with copy number of 1 without concomitant
single-nucleotide variants
One deleterious short variant (including insertions and deletions;
classification criteria provided below) with a concomitant loss of the
non-mutant PTEN allele defined by LOH with copy number of 1 or LOH
with copy number >1.
o Any protein truncating mutations, including nonsense mutations
and frameshift indels
o Any mutations in the consensus splice donor and acceptor
sequence that disrupts the consensus, including insertions and
deletions
o Any missense or non-frameshift mutation that has been
confirmed somatic as described in the COSMIC database
o If there are two or more deleterious short variants under LOH,
the patient will not be eligible for the study.
Patients must meet the following general criteria for study entry:
• Signed Informed Consent Form(s)
• Woman or man age≥ 18 years at the time of signing the Informed Consent Form
• Eastern Cooperative Oncology Group Performance Status of 0 or 1
• Adequate hematologic and organ function within 14 days before the first study
treatment on Day 1 of Cycle 1, defined by the following:
– Neutrophils (ANC ≥ 1500/µL)
– Hemoglobin ≥ 9 g/dL
– Platelet count ≥ 100,000/µL
– Serum albumin ≥ 3 g/dL
– Total bilirubin ≤ 1.5 × the upper limit of normal (ULN), with the following
exception:
Patients with known Gilbert syndrome who have serum bilirubin ≤ 3×ULN
may be enrolled.
– AST and ALT ≤ 2.5× ULN, with the following exception:
Patients with documented liver or bone metastases may have AST and
ALT ≤ 5×ULN.
– ALP ≤ 2× ULN, with the following exceptions:
Patients with known liver involvement may have ALP ≤ 5× ULN
Patients with known bone involvement may have ALP ≤ 7× ULN
– PTT (or aPTT) and INR ≤ 1.5 ×ULN (except for patients receiving
anticoagulation therapy)
Patients receiving heparin treatment should have a PTT (or aPTT)
between 1.5 and 2.5× ULN (or patient value before starting heparin
treatment). Patients receiving coumarin derivatives should have an INR
between 2.0 and 3.0 assessed in two consecutive measurements 1 to
4 days apart.
– Serum creatinine < 1.5 × ULN or creatinine clearance ≥50 mL/min based on
Cockcroft−Gault glomerular filtration rate estimation:
– Fasting total serum glucose ≤150 mg/dL and HbA1C ≤ 7.5%
• Life expectancy of at least 6 months
• For women of childbearing potential: agreement to remain abstinent (refrain from
heterosexual intercourse) or use contraceptive methods with a failure rate of <1%
per year during the treatment period and for at least 28 days after the last dose of
ipatasertib/placebo and 6 months after the last dose of paclitaxel, whichever occurs
later
– A woman is considered to be of childbearing potential if she is
postmenarcheal, has not reached a postmenopausal state (≥12 continuous
months of amenorrhea with no identified cause other than menopause),
and has not undergone surgical sterilization (removal of ovaries and/or
uterus).
– Examples of contraceptive methods with a failure rate of < 1% per year,
when used consistently and correctly, include combined (estrogen and
progestogen containing) hormonal contraception associated with inhibition
of ovulation, progestogen-only hormonal contraception associated with
inhibition of ovulation, bilateral tubal occlusion, male sterilization,
intrauterine hormone-releasing system, and sexual abstinence.
– Hormonal contraceptive methods may be used in accordance with specific
country and local requirements for patients with breast cancer.
– The reliability of sexual abstinence should be evaluated in relation to the
duration of the clinical trial and the preferred and usual lifestyle of the
patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or
postovulation methods) and withdrawal are not acceptable methods of
contraception.
• For men: agreement to remain abstinent (refrain from heterosexual intercourse) or
use contraceptive measures, and agreement to refrain from donating sperm, as
defined below:
– With female partners of childbearing potential, men must remain abstinent
or use a condom plus an additional contraceptive method that together
result in a failure rate of < 1% per year during the treatment period and for
28 days after the last dose of ipatasertib or 6 months after the last dose of
paclitaxel, whichever occurs later. Men must refrain from donating sperm
during this same period.
– With pregnant female partners, men must remain abstinent or use a
condom during the treatment period and for 28 days after the last dose of
ipatasertib or 6 months after the last dose of paclitaxel, whichever occurs
later, to avoid exposing the embryo.
– Examples of contraceptive methods with a failure rate of < 1% per year,
when used consistently and correctly, include combined (estrogen and
progestogen containing) hormonal contraception associated with inhibition
of ovulation, progestogen-only hormonal contraception associated with
inhibition of ovulation, bilateral tubal occlusion, male sterilization,
intrauterine hormone-releasing system, and sexual abstinence.
– The reliability of sexual abstinence should be evaluated in relation to the
duration of the clinical trial and the preferred and usual lifestyle of the
patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or
postovulation methods) and withdrawal are not acceptable methods of
contraception.
Disease-Specific Inclusion Criteria
Patients must meet the following disease-specific criteria for study entry:
• Histologically documented TNBC or HR+/HER2– adenocarcinoma of the breast that
is locally advanced or metastatic and is not amenable to resection with curative
intent
– Receptor status at study entry should correspond to the evaluation of the
most recent biopsy (non−fine-needle aspiration [FNA] sample), as
assessed locally (or centrally, if not available locally) according to the
ASCO/CAP guidelines (see Appendix 3 and Appendix 4):
HER2+ is defined as one of the following: immunohistochemistry 3+ or
in situ hybridization positive
ER or PgR positivity is defined as ≥ 1% of tumor cell nuclei immunoreactive
to the respective hormonal receptor
TNBC is defined as HER2–, ER–, and PgR– (required for eligibility for
Cohort A)
HR+/HER2– is defined as HER2– and ER+ and/or PgR+ (required for
eligibility for Cohort B)
• Measurable disease according to RECIST v1.1
• Submission of a formalin-fixed, paraffin-embedded tumor (FFPE) tissue block or a
minimum of 20 freshly cut unstained, serial tumor slides from the most recently
collected tumor tissue for central molecular analysis (mandatory NGS testing for
eligibility [PIK3CA/AKT1/PTEN-altered status] and for other protocol-mandated
secondary and exploratory assessments). Cytologic or FNA samples are not
acceptable. Tumor tissue from bone metastases that is subject to decalcification is
not acceptable.
– If the specimen is either insufficient or unavailable, the patient may still be
eligible if the patient can provide a tissue block (preferred) or a minimum of
20 unstained serial slides from an older archival tumor tissue or is willing to
consent to and undergo an additional pretreatment core or excisional
biopsy of the non-target lesion (if it is assessable and the biopsy can be
safely obtained). In general, a minimum of three core biopsies for NGS
testing are required.
• Valid results confirming PIK3CA/AKT1/PTEN-altered status in tumor tissue, defined
as the presence of one or more of the following by NGS:
– AKT1 missense mutations that result in amino acid substitution at the
following residues E17, L52, or Q79
– PIK3CA missense mutations that result in amino acid substitution at the
following residues R88, G106, K111, G118, N345, C420, E453, E542,
E545, Q546, M1043, H1047, or G1049
– PTEN alterations that meet any of the following criteria:
Homozygous deletion (copy number of 0)
Dominant negative short variant (e.g., C124S, G129E, R130X;
Papa et al. 2014)
Loss of heterozygosity (LOH) with copy number of 1 without concomitant
single-nucleotide variants
One deleterious short variant (including insertions and deletions;
classification criteria provided below) with a concomitant loss of the
non-mutant PTEN allele defined by LOH with copy number of 1 or LOH
with copy number >1.
o Any protein truncating mutations, including nonsense mutations
and frameshift indels
o Any mutations in the consensus splice donor and acceptor
sequence that disrupts the consensus, including insertions and
deletions
o Any missense or non-frameshift mutation that has been
confirmed somatic as described in the COSMIC database
o If there are two or more deleterious short variants under LOH,
the patient will not be eligible for the study.
Exclusion Criteria
General Exclusion Criteria
Patients who meet any of the following general criteria will be excluded from study entry:
• Inability to comply with study and follow-up procedures
• History of malabsorption syndrome or other condition that would interfere with
enteral absorption or results in the inability or unwillingness to swallow pills
• Active infection requiring antibiotics
• Known HIV infection
• Known clinically significant history of liver disease consistent with Child-Pugh
Class B or C, including active viral or other hepatitis (e.g., positive for hepatitis B
surface antigen [HBsAg] or hepatitis C virus [HCV] antibody at screening), current
drug or alcohol abuse, or cirrhosis
– Patients with past hepatitis B virus (HBV) infection or resolved HBV
infection (defined as having a negative HBsAg test and a positive antibody
to hepatitis B core antigen [HBcAg] antibody test) are eligible.
– Patients positive for HCV antibody are eligible only if polymerase chain
reaction (PCR) is negative for HCV RNA.
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
prior to Day 1 of Cycle 1 or anticipation of need for a major surgical procedure
during the course of the study
– Placement of a vascular access device is not considered major surgery.
• Pregnant or breastfeeding, or intending to become pregnant during the study or
within 28 days after the last dose of ipatasertib/placebo and within 6 months after
the last dose of paclitaxel, whichever occurs later
– Women of childbearing potential (who are not postmenopausal with
≥ 12 months of non-therapy induced amenorrhea nor surgically sterile)
must have a negative serum pregnancy test result within 48 hours prior to
initiation of study drug.
• New York Heart Association Class II, III, or IV heart failure; left ventricular ejection
fraction < 50%; or active ventricular arrhythmia requiring medication
• Current unstable angina or history of myocardial infarction within 6 months prior to
Day 1 of Cycle 1
• Congenital long QT syndrome or screening QT interval corrected using Fridericia's
formula (QTcF) > 480 milliseconds
• History or presence of an abnormal ECG that is clinically significant in the
investigator's opinion, including complete left bundle branch block, second- or
third-degree heart block, or evidence of prior myocardial infarction
• Need for chronic corticosteroid therapy of ≥ 10 mg of prednisone per day
or an equivalent dose of other anti-inflammatory corticosteroids
or immunosuppressants for a chronic disease
• Treatment with approved or investigational cancer therapy within 14 days prior to
Day 1 of Cycle 1
• Any other disease, metabolic dysfunction, physical examination finding, or clinical
laboratory finding that, in the investigator's opinion, gives reasonable suspicion of a
disease or condition that contraindicates the use of an investigational drug or that
may affect the interpretation of the results or render the patient at high risk from
treatment complications
Patients who meet any of the following general criteria will be excluded from study entry:
• Inability to comply with study and follow-up procedures
• History of malabsorption syndrome or other condition that would interfere with
enteral absorption or results in the inability or unwillingness to swallow pills
• Active infection requiring antibiotics
• Known HIV infection
• Known clinically significant history of liver disease consistent with Child-Pugh
Class B or C, including active viral or other hepatitis (e.g., positive for hepatitis B
surface antigen [HBsAg] or hepatitis C virus [HCV] antibody at screening), current
drug or alcohol abuse, or cirrhosis
– Patients with past hepatitis B virus (HBV) infection or resolved HBV
infection (defined as having a negative HBsAg test and a positive antibody
to hepatitis B core antigen [HBcAg] antibody test) are eligible.
– Patients positive for HCV antibody are eligible only if polymerase chain
reaction (PCR) is negative for HCV RNA.
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
prior to Day 1 of Cycle 1 or anticipation of need for a major surgical procedure
during the course of the study
– Placement of a vascular access device is not considered major surgery.
• Pregnant or breastfeeding, or intending to become pregnant during the study or
within 28 days after the last dose of ipatasertib/placebo and within 6 months after
the last dose of paclitaxel, whichever occurs later
– Women of childbearing potential (who are not postmenopausal with
≥ 12 months of non-therapy induced amenorrhea nor surgically sterile)
must have a negative serum pregnancy test result within 48 hours prior to
initiation of study drug.
• New York Heart Association Class II, III, or IV heart failure; left ventricular ejection
fraction < 50%; or active ventricular arrhythmia requiring medication
• Current unstable angina or history of myocardial infarction within 6 months prior to
Day 1 of Cycle 1
• Congenital long QT syndrome or screening QT interval corrected using Fridericia's
formula (QTcF) > 480 milliseconds
• History or presence of an abnormal ECG that is clinically significant in the
investigator's opinion, including complete left bundle branch block, second- or
third-degree heart block, or evidence of prior myocardial infarction
• Need for chronic corticosteroid therapy of ≥ 10 mg of prednisone per day
or an equivalent dose of other anti-inflammatory corticosteroids
or immunosuppressants for a chronic disease
• Treatment with approved or investigational cancer therapy within 14 days prior to
Day 1 of Cycle 1
• Any other disease, metabolic dysfunction, physical examination finding, or clinical
laboratory finding that, in the investigator's opinion, gives reasonable suspicion of a
disease or condition that contraindicates the use of an investigational drug or that
may affect the interpretation of the results or render the patient at high risk from
treatment complications
The Estimated Number of Participants
-
Taiwan
30 participants
-
Global
450 participants
