A Study Assessing the Safety and Efficacy of Adding Ipatasertib to Paclitaxel Treatment in Participants With Breast Cancer That Has Spread Beyond the Initial Site, and the Cancer Does Not Have Certain Hormonal Receptors

NCT ID: NCT02162719

Last Updated: 2021-03-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 124 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-08-19
• Study Completion Date: 2019-08-31

Brief Summary

This multicenter, randomized, double-blind study will estimate the efficacy, safety and tolerability of ipatasertib combined with paclitaxel compared with placebo combined with paclitaxel in participants with inoperable locally advanced or metastatic triple-negative breast cancer (mTNBC), as measured by progression-free survival (PFS) in all participants and in participants with phosphatase and tensin homolog (PTEN)-low tumors.

Conditions

Breast Neoplasms

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Ipatasertib + Paclitaxel

Participants randomised to receive paclitaxel 80 mg/m\^2, intravenously on Days 1, 8, and 15 along with ipatasertib 400 mg, orally, once daily from Days 1-21 in each cycle of 28 days until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.

Group Type: EXPERIMENTAL

Ipatasertib

Intervention Type: DRUG

Participants received ipatasertib orally 400 milligrams (mg) daily on Days 1-21 of each 28-day cycle.

Paclitaxel

Intervention Type: DRUG

Participants received paclitaxel 80 milligrams per square meter (mg/m\^2) intravenously (IV) on Days 1, 8, and 15 of each cycle.

Placebo + Paclitaxel

Participants randomised to receive paclitaxel 80 mg/m\^2, intravenously on Days 1, 8, and 15 along with placebo matching ipatasertib, orally, once daily from Days 1-21 in each cycle of 28 days until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.

Group Type: PLACEBO_COMPARATOR

Paclitaxel

Intervention Type: DRUG

Participants received paclitaxel 80 milligrams per square meter (mg/m\^2) intravenously (IV) on Days 1, 8, and 15 of each cycle.

Placebo

Intervention Type: DRUG

Participants received oral placebo matched to ipatasertib, daily on Days 1-21 of each 28-day cycle.

Interventions

Ipatasertib

Participants received ipatasertib orally 400 milligrams (mg) daily on Days 1-21 of each 28-day cycle.

Intervention Type: DRUG

Paclitaxel

Participants received paclitaxel 80 milligrams per square meter (mg/m\^2) intravenously (IV) on Days 1, 8, and 15 of each cycle.

Intervention Type: DRUG

Placebo

Participants received oral placebo matched to ipatasertib, daily on Days 1-21 of each 28-day cycle.

Intervention Type: DRUG

Other Intervention Names

GDC-0068

Eligibility Criteria

Inclusion Criteria

• Histologically documented triple-negative adenocarcinoma of the breast that is inoperable locally advanced or metastatic and is not amenable to resection with curative intent
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Availability of a representative formalin-fixed, paraffin-embedded (FFPE) tumor specimen, required prior to randomization
• Measurable disease, according to the RECIST v1.1
• Adequate hematologic and organ function within 14 days before the first study treatment
• For female participants of childbearing potential, agreement (by both participant and partner) to use an effective form of contraception for the duration of the study and for 6 months after last dose of study treatment

Exclusion Criteria

• Any previous therapy, including chemotherapy or hormonal or targeted therapy, for inoperable locally advanced or metastatic triple-negative adenocarcinoma of the breast. Participants may have received prior neoadjuvant or adjuvant chemotherapy and/or radiation treatment for locally advanced triple negative adenocarcinoma, provided all treatments were completed greater than or equal to (>/=) 6 months prior to Cycle 1 Day 1. Locally recurrent disease must not be amenable to resection with curative intent
• Any radiation treatment to metastatic site within 28 days of Cycle 1, Day 1
• Known Human Epidermal Growth Factor Receptor 2 (HER2) positive, erythrocyte receptor (ER) positive, or progesterone receptor (PR) positive breast cancer
• Previous therapy with Akt, PI3K, and/or mTOR inhibitors
• Major surgical procedure, open biopsy, or significant traumatic injury within 30 days prior to Cycle 1, Day 1 or anticipation of need for a major surgical procedure during the course of the study
• Known presence of the brain or spinal cord metastasis, as determined by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation during screening or prior radiographic assessments

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Genentech, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

St Jude Heritage Medical Group

Fullerton, California, United States

Cedars Sinai Medical Center

Los Angeles, California, United States

Cancer Care Assoc Med Group

Los Angeles, California, United States

UCLA Medical Center

Santa Monica, California, United States

Holycross Medical Group

Fort Lauderdale, Florida, United States

Memorial Healthcare System

Hollywood, Florida, United States

Hematology Oncology Associates of the Treasure Coast

Port Saint Lucie, Florida, United States

Rush University Medical Center

Chicago, Illinois, United States

Cancer Center of Kansas

Wichita, Kansas, United States

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, United States

Comprehensive Cancer Centers of Nevada

Henderson, Nevada, United States

Carolinas Healthcare System

Charlotte, North Carolina, United States

The WEST CLINIC, P.C.

Memphis, Tennessee, United States

MD Anderson Cancer Center

Houston, Texas, United States

Northern Utah Associates

Ogden, Utah, United States

Northwest Medical Specialties

Lakewood, Washington, United States

West Virginia University Hospitals Inc

Morgantown, West Virginia, United States

Sint Augustinus Wilrijk

Wilrijk, , Belgium

Institut Bergonié Centre Régional de Lutte Contre Le Cancer de Bordeaux Et Sud Ouest

Bordeaux, , France

Centre Francois Baclesse

Caen, , France

Centre Régional de Lutte Contre Le Cancer Val D'aurelle Paul Lamarque

Montpellier, , France

Hopital Saint Louis; Oncologie Medicale

Paris, , France

Clinique Armoricaine de Radiol

Saint-Brieuc, , France

Istituto Nazionale Tumori Fondazione G. Pascale

Napoli, Campania, Italy

Istituto Nazionale dei Tumori; Divisione Oncologia Chirurgica e Ginecologica

Milan, Lombardy, Italy

Istituto Oncologico Veneto IRCCS Farmacia Ospedaliera

Padua, Veneto, Italy

National University Hospital; National University Cancer Institute, Singapore (NCIS)

Singapore, , Singapore

National Cancer Centre

Singapore, , Singapore

National Cancer Center

Goyang-si, , South Korea

Seoul National University Bundang Hospital

Seongnam-si, , South Korea

Seoul National University Hospital

Seoul, , South Korea

Severance Hospital, Yonsei University Health System

Seoul, , South Korea

Asan Medical Center

Seoul, , South Korea

Korea University Guro Hospital

Seoul, , South Korea

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Institut Catala d Oncologia Hospital Duran i Reynals

Barcelona, , Spain

Complejo Hospitalario de Jaen

Jaén, , Spain

MD Anderson Cancer Center

Madrid, , Spain

HOSPITAL DE MADRID NORTE SANCHINARRO- CENTRO INTEGRAL ONCOLOGICO CLARA CAMPAL; Servicio de Farmacia

Madrid, , Spain

Hospital Virgen del Rocio

Seville, , Spain

China Medical University Hospital

North Dist., , Taiwan

Chi Mei Medical Center, Yong kang; Endocrinology

Tainan City, , Taiwan

National Taiwan University Hospital

Taipei, , Taiwan

Chang Gung Medical Foundation - Linkou; Dept of Surgery

Taoyuan District, , Taiwan

Countries

United States; Belgium; France; Italy; Singapore; South Korea; Spain; Taiwan

References

Kim SB, Dent R, Im SA, Espie M, Blau S, Tan AR, Isakoff SJ, Oliveira M, Saura C, Wongchenko MJ, Kapp AV, Chan WY, Singel SM, Maslyar DJ, Baselga J; LOTUS investigators. Ipatasertib plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer (LOTUS): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol. 2017 Oct;18(10):1360-1372. doi: 10.1016/S1470-2045(17)30450-3. Epub 2017 Aug 8.

Reference Type: DERIVED

PMID: 28800861 (View on PubMed)

Other Identifiers

2014-000469-35

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GO29227

Identifier Type: -

Identifier Source: org_study_id