Breast Cancer
Conditions
Brief summary
A study to evaluate the efficacy and safety of triplet combination of inavolisib plus ribociclib and fulvestrant versus placebo plus ribociclib and fulvestrant in the first-line setting in participants with endocrine-therapy-resistant hormone receptor (HR)-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC).
Interventions
DRUGInavolisib
Inavolisib will be administered as per the schedule mentioned in the protocol.
DRUGRibociclib
Ribociclib will be administered as per the schedule mentioned in the protocol.
DRUGFulvestrant
Fulvestrant will be administered as per the schedule mentioned in the protocol.
DRUGPlacebo
Placebo will be administered as per the schedule mentioned in the protocol.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
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 that is locally advanced or metastatic and is not amenable to surgical or radiation therapy with curative intent * Documented estrogen receptor (ER)-positive and/or progesterone receptor (PR)-positive tumor according to American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines, defined as \>=1% of tumor cells stained positive based on the most recent tumor biopsy and assessed locally (Allison et al. 2020) * Participants must not have received any prior systemic therapy for locally advanced unresectable or metastatic breast cancer (mBC) and must have progressed during adjuvant endocrine-based treatment or within 12 months after completing adjuvant endocrine-based therapy with an aromatase inhibitor or tamoxifen * Confirmed biomarker eligibility as documented through central laboratory testing of a tumor tissue sample documenting both the lack of a phosphatidylinositol-4,5-biphosphate 3-kinase catalytic subunit alpha gene (PIK3CA) mutation and the presence of heterozygous loss of chromosome 8p (i.e., PIK3CAnmd and chr8p loss) * Measurable disease per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
Exclusion criteria
* Metaplastic breast cancer * Radiotherapy within 2 weeks before randomization * Appropriate for treatment with cytotoxic chemotherapy at time of entry into the study, as per national or local treatment guidelines (e.g., participants with visceral crisis) * Type 2 diabetes requiring ongoing systemic treatment at the time of study entry; or any history of Type 1 diabetes * Known and untreated, or active Central nervous system (CNS) metastases (progressing or requiring anticonvulsants or corticosteroids for symptomatic control). Participants with a history of treated CNS metastases are eligible * Any history of leptomeningeal disease or carcinomatous meningitis
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of Participants With Confirmed Objective Response (cORR) | Up to approximately 2 years |
Secondary
| Measure | Time frame |
|---|---|
| Progression-Free Survival (PFS) | Up to approximately 2 years |
| Overall Survival (OS) | Up to approximately 2 years |
| Duration of Response (DOR) | Up to approximately 2 years |
| Percentage of Participants with Clinical Benefit (CBR) | Up to approximately 2 years |
| Percentage of Participants with Adverse Events (AEs) | Up to approximately 2 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 approximately 2 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 approximately 2 years |
| Change From Baseline in Symptomatic Treatment Toxicities as Assessed Through use of the PRO-CTCAE | Baseline, Up to approximately 2 years |
| Change from Baseline in Treatment Side-effect Bother as Assessed Through use of the FACT-G GP5 Item | Baseline, Up to approximately 2 years |
Countries
Argentina, Brazil, Canada, France, Germany, Italy, Mexico, Poland, South Korea, Spain, United Kingdom, United States
Contacts
CONTACTReference Study ID Number: CO46274 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