A Clinical Trial of Ipatasertib plus chemotherapy for Patients withAdvanced Triple Negative Breast Cancer or Hormone Receptor–Positive,HER2-Negative Breast Cancer that has a change in the PIK3CA/AKT1/PTENGene
- Conditions
- ocally advanced unresectable or metastatic triple-negative (estrogenreceptor, progesterone receptor, and HER2 negative) breast cancer orlocally advanced unresectable or metastatic hormone receptor–positive,HER2-negative breast cancer with PIK3CA/AKT1/PTEN-altered tumorand no prior chemotherapy in the advanced settingTherapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2017-001548-36-PL
- Lead Sponsor
- F. Hoffmann-La Roche Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 450
General Inclusion Criteria
- 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
- 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 Ipat/placebo, 5 months after the
last dose of Atezo and 6 months after the last dose of Pac, whichever
occurs later, and agreement to refrain from donating eggs during this
same period
- For men: agreement to remain abstinent (refrain from heterosexual
intercourse) or use contraceptive measures, and agreement to refrain
from donating sperm 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
- For any patients enrolled in the extended enrollment phase (i.e.,
China extension phase): patient is a current resident of mainland China,
Hong Kong, or Taiwan, and of Chinese ancestry
Disease-Specific Inclusion Criteria
- Locally assessed, 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
- Measurable disease according to Response Evaluation Criteria in Solid
Tumors (RECIST) v1.1
- Eligible for taxane monotherapy
- HR+/HER2– breast cancer that is not considered appropriate for
endocrine-based therapy and that meets one of the following inclusion
criteria:
o Patient has recurrent disease (locoregional or metastatic) during
adjuvant endocrine therapy (i.e. =5 years of being on therapy)
o If patient has de novo metastatic disease, patient has progressive
disease within 6 months of being on first-line endocrine treatment of
metastatic disease.
- 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. Cytologic or FNA samples are not acceptable. Tumor
tissue from bone metastases that is subject to decalcification is not
acceptable.
- If the patient already has PIK3CA/AKT1/PTEN alteration results
available from the FMI commercial tissue-based NGS assay known as
FoundationONE CDx TM, then reduced tissue requirements may be
required (upon approval by the Medical Monitor)
o This tumor tissue sample is required to be submitted as described
above for all patients, i.e., if local assessment of PIK3CA/AKT1/PTEN
alteration status or central ctDNA is used to confirm biomarker eligibility
tumor tissue is still required to assess alteration status centrally
- Confirmation of biomarker eligibility, i.e., valid results from either
central testing or local testing (at a CLIA or equivalently accredited
laboratory) of tumor tissue or blood demonstrating PIK3CA/AKT1/PTENaltered status
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 360
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 90
General Exclusion Criteria:
- 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 systemic anti-microbial treatment (including antibiotics anti-fungals, anti-viral agents)
- Known HIV infection and clinically significant history of liver disease
consistent with Child-Pugh Class B or C, including active viral or other
hepatitis, current drug or alcohol abuse, or cirrhosis-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-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- 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, may contraindicate the use of an investigational drug
Disease-Specific Exclusion Criteria:
- History of or known presence of brain or spinal cord metastases, as determined by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation during screening or prior radiographic assessments
- Any previous chemotherapy for inoperable locally advanced or metastatic TNBC or HR+/HER2– adenocarcinoma of the breast
- Unresolved, clinically significant toxicity from prior therapy
- Patients with HR+/HER2– breast cancer, for whom endocrine therapy (alone or with approved targeted therapy such as CDK4/6 inhibitors or everolimus) is considered an appropriate option per local clinical guidelines, i.e., all patients enrolled must not be appropriate candidates for endocrine-based therapy at time of screening
- Patients who have received palliative radiation treatment to peripheral sites for pain control and whose last treatment was completed 14 days prior to Day 1 of Cycle 1 may be enrolled in the study if they have recovered from all acute, reversible effects (e.g., to Grade 1 or resolved by enrollment)
- Uncontrolled pleural effusion, pericardial effusion, or ascites tumorrelated pain, and hypercalcemia or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy
- Malignancies other than breast cancer within 5 years prior to Day 1 of
Cycle 1 except for appropriately treated carcinoma in situ of the cervix,
non melanoma skin carcinoma, or Stage I uterine cancer
Ipatasertib-Specific Exclusion Criteria:
- History of Type I or Type II diabetes mellitus requiring insulin
- Grade >=2 uncontrolled or untreated hypercholesterolemia or hypertriglyceridemia
- History of or active inflammatory bowel disease or active bowel inflammation
- Lung disease: pneumonitis, inters
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method