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
LOTUS
A Randomized, Phase II, Multi-Center, Placebo-Controlled Study of Ipatasertib (GDC-0068), an Inhibitor of Akt, in Combination With Paclitaxel as Front-Line Treatment for Patients With Metastatic Triple-Negative Breast Cancer
2 other identifiers
interventional
124
8 countries
44
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Aug 2014
Longer than P75 for phase_2
44 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 11, 2014
CompletedFirst Posted
Study publicly available on registry
June 13, 2014
CompletedStudy Start
First participant enrolled
August 19, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 7, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
August 31, 2019
CompletedResults Posted
Study results publicly available
January 11, 2021
CompletedMarch 10, 2021
February 1, 2021
1.8 years
June 11, 2014
December 15, 2020
February 18, 2021
Conditions
Outcome Measures
Primary Outcomes (2)
Progression Free Survival (PFS)
PFS was defined as the time from randomization to the first occurrence of disease progression, as determined by investigator review of tumor assessments by RECIST, v1.1 or death on study (\<=30 days after the last dose of study treatment regimen) from any cause, whichever occurred first.
Baseline up to 30 days after the last dose of study drug administration (Clinical Cut Off Date: 07 June 2016)
PFS in Participants With Phosphatase and Tensin Homolog (PTEN)-Low Tumors
PFS was defined as the time from randomization to the first occurrence of disease progression, as determined by investigator review of tumor assessments by RECIST, v1.1 or death on study (\<=30 days after the last dose of study treatment regimen) from any cause, whichever occurred first.
Baseline up to 30 days after the last dose of study drug administration (Clinical Cut Off Date: 07 June 2016)
Secondary Outcomes (18)
PFS in Participants With Phosphatidylinositol-4,5-bisphosphate 3-kinase Catalytic Subunit Alpha (PIK3CA)/ Protein Kinase B (AKT1)/ PTEN-altered Tumors
Baseline up to 30 days after the last dose of study drug administration (Clinical Cut Off Date: 07 June 2016)
Overall Survival (OS)
Baseline up to 30 days after the last dose of study drug administration (Clinical Cut Off Date: 31 August 2019)
OS in Participants With PTEN-Low Tumors
Baseline up to 30 days after the last dose of study drug administration (Clinical Cut Off Date: 31 August 2019)
OS in Participants With PIK3CA/AKT1/PTEN-altered Tumors
Baseline up to 30 days after the last dose of study drug administration (Clinical Cut Off Date: 31 August 2019)
Objective Response Rate (ORR)
Baseline up to every 8 weeks until documented disease progression (Clinical Cut Off Date: 07 June 2016)
- +13 more secondary outcomes
Study Arms (2)
Ipatasertib + Paclitaxel
EXPERIMENTALParticipants 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.
Placebo + Paclitaxel
PLACEBO COMPARATORParticipants 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.
Interventions
Participants received ipatasertib orally 400 milligrams (mg) daily on Days 1-21 of each 28-day cycle.
Participants received paclitaxel 80 milligrams per square meter (mg/m\^2) intravenously (IV) on Days 1, 8, and 15 of each cycle.
Participants received oral placebo matched to ipatasertib, daily on Days 1-21 of each 28-day cycle.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Genentech, Inc.lead
Study Sites (44)
St Jude Heritage Medical Group
Fullerton, California, 92835, United States
Cedars Sinai Medical Center
Los Angeles, California, 90048, United States
Cancer Care Assoc Med Group
Los Angeles, California, 90095-1772, United States
UCLA Medical Center
Santa Monica, California, 90404, United States
Holycross Medical Group
Fort Lauderdale, Florida, 33308, United States
Memorial Healthcare System
Hollywood, Florida, 33021, United States
Hematology Oncology Associates of the Treasure Coast
Port Saint Lucie, Florida, 34952, United States
Rush University Medical Center
Chicago, Illinois, 60612, United States
Cancer Center of Kansas
Wichita, Kansas, 67214-3728, United States
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114, United States
Comprehensive Cancer Centers of Nevada
Henderson, Nevada, 89014, United States
Carolinas Healthcare System
Charlotte, North Carolina, 28208, United States
The WEST CLINIC, P.C.
Memphis, Tennessee, 38119, United States
MD Anderson Cancer Center
Houston, Texas, 77030, United States
Northern Utah Associates
Ogden, Utah, 84403, United States
Northwest Medical Specialties
Lakewood, Washington, 98499, United States
West Virginia University Hospitals Inc
Morgantown, West Virginia, 26056, United States
Sint Augustinus Wilrijk
Wilrijk, 2610, Belgium
Institut Bergonié Centre Régional de Lutte Contre Le Cancer de Bordeaux Et Sud Ouest
Bordeaux, 33076, France
Centre Francois Baclesse
Caen, 14076, France
Centre Régional de Lutte Contre Le Cancer Val D'aurelle Paul Lamarque
Montpellier, 34298, France
Hopital Saint Louis; Oncologie Medicale
Paris, 75475, France
Clinique Armoricaine de Radiol
Saint-Brieuc, 22015, France
Istituto Nazionale Tumori Fondazione G. Pascale
Napoli, Campania, 80131, Italy
Istituto Nazionale dei Tumori; Divisione Oncologia Chirurgica e Ginecologica
Milan, Lombardy, 20133, Italy
Istituto Oncologico Veneto IRCCS Farmacia Ospedaliera
Padua, Veneto, 35128, Italy
National University Hospital; National University Cancer Institute, Singapore (NCIS)
Singapore, 119228, Singapore
National Cancer Centre
Singapore, 169610, Singapore
National Cancer Center
Goyang-si, 10408, South Korea
Seoul National University Bundang Hospital
Seongnam-si, 13605, South Korea
Seoul National University Hospital
Seoul, 03080, South Korea
Severance Hospital, Yonsei University Health System
Seoul, 03722, South Korea
Asan Medical Center
Seoul, 05505, South Korea
Korea University Guro Hospital
Seoul, 08308, South Korea
Hospital Universitari Vall d'Hebron
Barcelona, 08035, Spain
Institut Catala d Oncologia Hospital Duran i Reynals
Barcelona, 08908, Spain
Complejo Hospitalario de Jaen
Jaén, 23007, Spain
MD Anderson Cancer Center
Madrid, 28033, Spain
HOSPITAL DE MADRID NORTE SANCHINARRO- CENTRO INTEGRAL ONCOLOGICO CLARA CAMPAL; Servicio de Farmacia
Madrid, 28050, Spain
Hospital Virgen del Rocio
Seville, 41013, Spain
China Medical University Hospital
North Dist., 40402, Taiwan
Chi Mei Medical Center, Yong kang; Endocrinology
Tainan, 710, Taiwan
National Taiwan University Hospital
Taipei, 10002, Taiwan
Chang Gung Medical Foundation - Linkou; Dept of Surgery
Taoyuan District, 333, Taiwan
Related Publications (1)
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.
PMID: 28800861DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Medical Communications
- Organization
- Hoffmann-La Roche
Study Officials
- STUDY DIRECTOR
Clinical Trials
Hoffmann-La Roche
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 11, 2014
First Posted
June 13, 2014
Study Start
August 19, 2014
Primary Completion
June 7, 2016
Study Completion
August 31, 2019
Last Updated
March 10, 2021
Results First Posted
January 11, 2021
Record last verified: 2021-02
Data Sharing
- IPD Sharing
- Will share
Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research\_and\_development/who\_we\_are\_how\_we\_work/clinical\_trials/our\_commitment\_to\_data\_sharing.htm).