Recruiting NCT06790693

A Study Evaluating the Efficacy and Safety of Inavolisib Plus CDK4/6 Inhibitor and Letrozole vs Placebo + CDK4/6i and Letrozole in Participants With Endocrine-Sensitive PIK3CA-Mutated, Hormone Receptor-Positive, HER2-Negative Advanced Breast Cancer

Phase III Interventional Breast Cancer

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied: The protocol lists: Inavolisib, Placebo, CDK4/6i, Letrozole.
Who it may be relevant to: Registry conditions: Breast Cancer. Basic parameters: from 18 years · All.
What needs checking: Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place: United States, Argentina, Australia, Brazil, Canada +15
Next step: Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Official title

A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of Inavolisib Plus a CDK4/6 Inhibitor and Letrozole Versus Placebo Plus a CDK4/6 Inhibitor and Letrozole in Patients With Endocrine-Sensitive PIK3CA-Mutated, Hormone Receptor-Positive, HER2-Negative Advanced Breast Cancer

Overview

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

Drug Inavolisib
Participants will receive oral inavolisib once daily (QD).
Drug Placebo
Participants will receive oral placebo QD.
Drug CDK4/6i
Participants will receive CDK4/6i on either Days 1-21 or Days 1-28 of each 28-day cycle.
Drug Letrozole
Participants will receive oral letrozole QD.

Primary outcome measures

Progression-Free Survival (PFS) [Time frame: From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to 7 years)]

Secondary outcome measures (12)

Overall Survival (OS) [Time frame: From randomization to death from any cause (up to 7 years)]
Investigator-assessed Objective Response Rate (ORR) [Time frame: Up to 7 years]
Investigator-assessed Duration of Response (DOR) [Time frame: 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) [Time frame: Up to 7 years]
Time to Confirmed Deterioration (TTCD) in Pain [Time frame: From baseline until end of follow-up (up to 7 years)]
TTCD in Physical Function [Time frame: From baseline until end of follow-up (up to 7 years)]
TTCD in Role Function [Time frame: From baseline until end of follow-up (up to 7 years)]
TTCD in Global Health Status [Time frame: From baseline until end of follow-up (up to 7 years)]
Percentage of Participants with Adverse Events [Time frame: 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) [Time frame: 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) [Time frame: Up to 7 years]
Change from Baseline in Symptomatic Treatment Toxicities as Assessed Through use of the PRO-CTCAE [Time frame: Baseline up to 7 years]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation: Randomized
Model: Parallel assignment
Masking: Double blind
Primary purpose: Treatment