Breast Cancer
Conditions
Brief summary
This study will evaluate the efficacy and safety of the combination of inavolisib plus a cyclin-dependent kinase 4 and 6 inhibitor (CDK4/6i) and letrozole versus placebo plus a CDK4/6i and letrozole in the first-line setting in participants with endocrine-sensitive PIK3CA-mutated hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), advanced breast cancer (ABC).
Interventions
DRUGInavolisib
Participants will receive oral inavolisib once daily (QD).
DRUGPlacebo
Participants will receive oral placebo QD.
DRUGCDK4/6i
Participants will receive CDK4/6i on either Days 1-21 or Days 1-28 of each 28-day cycle.
DRUGLetrozole
Participants will receive oral letrozole QD.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Women or men with histologically or cytologically confirmed carcinoma of the breast * Documented ER-positive and/or progesterone receptor-positive tumor according to American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines * Documented HER2-negative tumor according to ASCO/CAP guidelines * De-novo HR+ , HER2- ABC, or, alternatively, relapsed HR+ , HER2- ABC after at least 2 years of standard neoadjuvant/adjuvant endocrine therapy without disease progression during that treatment and disease-free interval of at least 1 year since the completion of that treatment * Participants who have bilateral breast cancers which are both HR-positive and HER2-negative * Confirmation of biomarker eligibility * Consent to provide fresh or archival tumor tissue specimen * Measurable disease per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 * Adequate hematologic and organ function within 14 days prior to initiation of study treatment
Exclusion criteria
* Pregnant or breastfeeding, or intention of becoming pregnant during the study or within the time frame in which contraception is required * Metaplastic breast cancer * Any prior systemic therapy for locally advanced unresectable or metastatic breast cancer * Type 2 diabetes requiring ongoing systemic treatment at the time of study entry; or any history of Type 1 diabetes * Any history of leptomeningeal disease or carcinomatous meningitis * Known and untreated, or active CNS metastases. Participants with a history of treated CNS metastases are eligible * Active inflammatory or infectious conditions in either eye or history of idiopathic or autoimmune-associated uveitis in either eye * Symptomatic active lung disease * History of or active inflammatory bowel disease * Any active bowel inflammation * Prior hematopoietic stem cell or bone marrow transplantation * Treatment with strong cytochrome P450 (CYP) 3A4 inhibitors or strong CYP3A4 inducers within 4 weeks or 5 drug-elimination half-lives, prior to initiation of study treatment
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression-Free Survival (PFS) | From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to 7 years) |
Secondary
| Measure | Time frame |
|---|---|
| Overall Survival (OS) | From randomization to death from any cause (up to 7 years) |
| Investigator-assessed Objective Response Rate (ORR) | Up to 7 years |
| Investigator-assessed Duration of Response (DOR) | From the first occurrence of a confirmed objective response to the first occurrence of disease progression or death from any cause, whichever occurs first (up to 7 years) |
| Investigator-assessed Clinical Benefit Rate (CBR) | Up to 7 years |
| Time to Confirmed Deterioration (TTCD) in Pain | From baseline until end of follow-up (up to 7 years) |
| TTCD in Physical Function | From baseline until end of follow-up (up to 7 years) |
| TTCD in Role Function | From baseline until end of follow-up (up to 7 years) |
| TTCD in Global Health Status | From baseline until end of follow-up (up to 7 years) |
| Percentage of Participants with Adverse Events | From baseline until end of follow-up (up to 7 years) |
| Number of Participants Reporting Presence, Frequency, Severity, and/or Degree of Interference with Daily Function of Symptomatic Treatment Toxicities Assessed by NCI Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (PRO-CTCAE) | Up to 7 years |
| Number of Participants Reporting Each Response Option for Treatment Side-effect Bother Single-item General Population, Question 5 (GP5) from the Functional Assessment of Cancer Therapy-General Questionnaire; (FACT-G) | Up to 7 years |
| Change from Baseline in Symptomatic Treatment Toxicities as Assessed Through use of the PRO-CTCAE | Baseline up to 7 years |
| Change from Baseline in Treatment Side-effect Bother as Assessed Through use of the FACT-G GP5 Item | Baseline up to 7 years |
Countries
Argentina, Australia, Brazil, Canada, China, France, Germany, Italy, Japan, Mexico, Poland, Puerto Rico, South Africa, South Korea, Spain, Switzerland, Taiwan, Turkey (Türkiye), United Kingdom, United States
Contacts
CONTACTReference Study ID Number: WO45654 https://forpatients.roche.com/ No attachments to email below.
CONTACTFastest response: use the inquiry form. https://www.gene.com/contact-us/submit-medical-inquiry
STUDY_DIRECTORClinical Trials
Hoffmann-La Roche
Outcome results
None listed