A Study to Test Inavolisib Treatments in Participants With Early-Stage, PIK3CA-Mutated Breast Cancer

Official title

A Phase II, Open-Label, Multicenter Study Evaluating the Safety and Efficacy of Neoadjuvant Treatment With Inavolisib Combinations in Patients With Untreated, Early-stage, PIK3CA-Mutated Breast Cancer

Overview

This study will evaluate the safety and efficacy of inavolisib combination therapies in participants with untreated, PIK3CA-mutated, Stage II-III, estrogen receptor (ER)-positive, Human Epidermal Growth Factor Receptor 2 (HER2)-negative breast cancer (BC).

Interventions

• Drug Inavolisib
  Inavolisib will be administered as per the schedule specified in the arms
• Drug Ribociclib
  Ribociclib will be administered as per the schedule specified in the arms
• Drug Letrozole
  Letrozole will be administered as per the schedule specified in the arms

Primary outcome measures

• Percentage of Participants with Adverse Events (AEs) [Time frame: From first dose up to 30 days after last dose (approximately 8 months)]

Secondary outcome measures (7)

• Percentage of Participants with Total Pathological Complete Response (pCR) [Time frame: Up to approximately 8 months]
• Percentage of Participants with Objective Response Rate (ORR), According to Modified Response Evaluation Criteria in Solid Tumors, Version 1.1 (mRECIST v1.1) [Time frame: Up to approximately 8 months]
• Change From Baseline in Ki-67 Levels by Immunohistochemistry (IHC) [Time frame: Baseline, Day 22 of Cycle 1 and at Surgery (up to approximately 8 months). One cycle = 28 days]
• Percentage of Participants Reporting Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire [Time frame: Up to approximately 8 months]
• Percentage of Participants Reporting Each Response Option at Each Time Point for the Treatment Side-Effect Bother Item (GP5) From the Functional Assessment of Cancer Therapy - General (FACT-G) Questionnaire [Time frame: Up to approximately 8 months]
• Change from Baseline in Symptomatic Treatment-Related Toxicities as Assessed Through use of the PRO-CTCAE [Time frame: Baseline, up to approximately 8 months]
• Change from Baseline in Treatment Side-Effect Bother as Assessed Through use of the FACT-G GP5 Item [Time frame: Baseline, up to approximately 8 months]

Eligibility criteria

Inclusion criteria

• Histologically confirmed operable or inoperable invasive Stage II-III BC according to American Joint Committee on Cancer (AJCC) TNM staging classification
• Candidate for neoadjuvant treatment and considered appropriate for endocrine combination therapy
• Willingness to undergo breast surgery (mastectomy or breast-conserving surgery) after neoadjuvant treatment (unless inoperable)
• Documented ER-positive tumor in accordance with current American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines
• Documented HER2-negative tumor in accordance with current ASCO/CAP guidelines
• Documented Ki-67 score >=5% as per local assessment
• Confirmed PIK3CA mutation

Exclusion criteria

• Stage IV (metastatic) BC
• Inflammatory BC (cT4d)
• Bilateral invasive BC
• History of ductal carcinoma in situ or lobular carcinoma in situ if they have received any systemic therapy for treatment or radiation therapy to the ipsilateral breast
• Previous systemic or local treatment for the primary BC currently under investigation (including excisional biopsy or any other surgery of the primary tumor and/or axillary lymph nodes, including sentinel lymph node biopsy, radiotherapy, cytotoxic, and endocrine treatments)
• Type 2 diabetes requiring ongoing systemic treatment at the time of study entry; or any history of Type 1 diabetes

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

Open label

Primary purpose

Treatment

Study locations

Germany · 7 centers

• Das Brustzentrum — Berlin
• HELIOS Klinikum Berlin-Buch — Berlin
• Universitätsklinikum "Carl Gustav Carus" der Technischen Universität Dresden — Dresden
• Kliniken Essen-Mitte — Essen
• Universitätsklinikum Heidelberg — Heidelberg
• St. Vincenz-Krankenhaus GmbH Paderborn Frauen- und Kinderklinik St. Louise — Paderborn
• HELIOS Klinikum Schwerin — Schwerin

Spain · 7 centers

• Vall d'Hebron Institute of Oncology (VHIO), Barcelona — Barcelona
• Hospital Clinic Barcelona — Barcelona
• Hospital General Universitario Gregorio Marañon — Madrid
• Hospital Universitario 12 de Octubre — Madrid
• Hospital Clinico Universitario de Salamanca — Salamanca
• Hospital Universitario Virgen Macarena — Seville
• Hospital Clínico Universitario de Valencia — Valencia

United States · 4 centers

• Los Angeles Cancer Network — Los Angeles
• Community Clinical Trials — Orange
• West Cancer Center — Germantown
• West Virginia University — Morgantown

Brazil · 4 centers

• Hospital Araujo Jorge — Goiânia
• Hospital do Cancer de Pernambuco - HCP — Recife
• Irmandade Da Santa Casa de Misericordia de Porto Alegre — Porto Alegre
• Clinica de Pesquisa e Centro de Estudos em Oncologia Ginecologica e Mamaria Ltda — São Paulo

Canada · 4 centers

• Sunnybrook Odette Cancer Centre — Toronto
• Centre Hospitalier de l'Universite de Montreal (CHUM) — Montreal
• Jewish General Hospital — Montreal
• McGill University Health Center — Montreal

South Korea · 4 centers

• Seoul National University Hospital — Seoul
• Severance Hospital, Yonsei University Health System — Seoul
• Asan Medical Center. — Seoul
• Samsung Medical Center — Seoul

Argentina · 3 centers

• Hospital Aleman de Buenos Aires — Buenos Aires
• Centro Médico Fleischer — Buenos Aires
• Centro Oncologico Korben — Ciudad Autonoma Buenos Aires

Identifiers

NCT: NCT07054190 · BO45853 · 2024-518811-20-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗