A Study Evaluating the Efficacy and Safety of Inavolisib + Palbociclib + Fulvestrant vs Placebo + Palbociclib + Fulvestrant in Participants With PIK3CA-Mutant, Hormone Receptor-Positive, HER2-Negative, Locally Advanced or Metastatic Breast Cancer
Inavolisib: Participants will receive oral inavolisib on Days 1-28 of each 28-day cycle.
Placebo: Participants will receive oral placebo on Days 1-28 of each 28-day cycle.
Palbociclib: Participants will receive oral palbociclib on Days 1-21 of each 28-day cycle.
Fulvestrant: Participants will receive intramuscular (IM) fulvestrant approximately every 4 weeks.
Study summary
This study will evaluate the efficacy, safety, and pharmacokinetics of inavolisib in combination with palbociclib and fulvestrant compared with placebo plus palbociclib and fulvestrant in participants with PIK3CA-mutant, hormone receptor (HR)-positive, HER2-negative locally advanced or metastatic breast cancer whose disease progressed during treatment or within 12 months of completing adjuvant endocrine therapy and who have not received prior systemic therapy for metastatic disease.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria
* Confirmed diagnosis of HR+/HER2- breast cancer
* Metastatic or locally advanced disease not amenable to curative therapy
* Progression of disease during adjuvant endocrine treatment or within 12 months of completing adjuvant endocrine therapy with an aromatase inhibitor or tamoxifen
* Receiving LHRH agonist therapy for at least 2 weeks prior to Day 1 of Cycle 1 if pre/peri-menopausal
* Confirmation of biomarker eligibility (detection of specified mutation(s) of PIK3CA via specified test)
* Consent to provide fresh or archival tumor tissue specimen
* Measurable disease per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1); evaluable "bone-only" disease is not eligible; "bone-only" disease with at least one measurable, soft-tissue component, even if considered disease that is limited to bone but has lytic or mixed lytic/blastic lesions and at least one measurable soft-tissue component per RECIST v1.1 may be eligible
* Eastern Cooperative Oncology Group Performance Status of 0 or 1
* Life expectancy of \> 6 months
* Adequate hematologic and organ function within 14 days prior to initiation of study treatment
Exclusion Criteria
* Metaplastic breast cancer
* Any history of leptomeningeal disease or carcinomatous meningitis
* Any prior systemic therapy for metastatic breast cancer
* Prior treatment with fulvestrant or any selective estrogen-receptor degrader, with the exception of participants that have received fulvestrant or any selective estrogen-receptor degrader as part of neoadjuvant therapy only and with treatment duration of no longer than 6 months
* Prior treatment with any PI3K, AKT, or mTOR inhibitor, or any agent whose mechanism of action is to inhibit the PI3K-AKT-mTOR pathway
* 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 CNS metastases. Patients with a history of treated CNS metastases may be eligible
* Active inflammatory or infectious conditions in either eye, or any eye conditions expected to require surgery during the study treatment period
* Symptomatic active lung disease, or requiring daily supplemental oxygen
* History of inflammatory bowel disease or active bowel inflammation
* Anti-cancer therapy within 2 weeks before study entry
* Investigational drug(s) within 4 weeks before randomization
* Prior radiotherapy to \>= 25% of bone marrow, or hematopoietic stem cell or bone marrow transplantation
* Chronic corticosteroid therapy or immunosuppressants
* Pregnant, lactating, or breastfeeding, or intending to become pregnant during the study or within 2 weeks after the final dose of study treatment
* Major surgical procedure, or significant traumatic injury, within 28 days prior to Day 1 of Cycle 1
Primary outcome measure(s)
Progression-Free Survival (PFS) — Up to 3.7 years PFS was defined as the time from randomization to the first occurrence of disease progression, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 or death from any cause (whichever occurs first). Progressive disease (PD) was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum in the study, including baseline, in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeter (mm). The appearance of one or more new lesions was also considered progression. Data for participants without the occurrence of PD or death as of the clinical cutoff date (CCOD) were censored at the time of the last tumor assessment prior to the CCOD. Median PFS was calculated using the Kaplan-Meier methodology.
Trial sites (135)
Facility
City
Region
Status
Beverly Hills Cancer Center
Beverly Hills
California
Massachusetts General Hospital.
Boston
Massachusetts
Memorial Sloan Kettering Cancer Center
New York
New York
Wake Forest University Baptist Medical Center
Winston-Salem
North Carolina
Sarah Cannon Research Institute / Tennessee Oncology
Chattanooga
Tennessee
Sarah Cannon Research Institute / Tennessee Oncology
Nashville
Tennessee
Texas Oncology - Central South
Austin
Texas
Texas Tech University Health Sciences Center
El Paso
Texas
Texas Oncology - Northeast Texas
Tyler
Texas
Northwest Medical Specialties
Tacoma
Washington
Centro de Investigaciones Médicas y Desarrollo LC S.R.L
Buenos Aires
Ciudad Autónoma de BuenosAires
Centro Oncologico Korben
Ciudad Autonoma Buenos Aires
Argentina
Hosp Provincial D. Centenarios
Rosario
Argentina
Macquarie University Hospital
Macquarie Park
New South Wales
Southern Medical Day Care Centre
Wollongong
New South Wales
Mater Adult Hospital
South Brisbane
Queensland
Princess Alexandra Hospital
Woolloongabba
Queensland
Western Health
Fitzroy
Victoria
Peninsula and South Eastern Haematology and Oncology Group
Frankston
Victoria
UZ Leuven Gasthuisberg
Leuven
Belgium
Santa Casa de Misericordia de Porto Alegre
Porto Alegre
Rio Grande do Sul
Arthur J.E. Child Comprehensive Cancer Center-Calgary
Calgary
Alberta
London Regional Cancer Program, London Health Sciences Centre, Baines Centre
London
Ontario
Ottawa Hospital
Ottawa
Ontario
Princess Margaret Cancer Center
Toronto
Ontario
Hopital du Saint Sacrement
Québec
Quebec
Beijing Cancer Hospital
Beijing
China
The First Hospital of Jilin University
Changchun
China
The First Affiliated Hospital, Chongqing Medical University
Chongqing
China
Fujian Medical University Union Hospital
Fujian
China
Sun Yet-sen University Cancer Center
Guangzhou
China
Zhejiang Cancer Hospital
Hangzhou
China
Harbin Medical University Cancer Hospital
Harbin
China
Fudan University Shanghai Cancer Center
Shanghai
China
Hebei Medical University Fourth Hospital
Shijiazhuang
China
Tianjin Cancer Hospital
Tianjin
China
Hubei Cancer Hospital
Wuhan
China
First Affiliated Hospital of Medical College of Xi'an Jiaotong University
Xi'an
China
Henan Cancer Hospital
Zhengzhou
China
Vejle Sygehus
Vejle
Denmark
+ 95 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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