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Breast NeoplasmsPhase 2LOTUSNCT02162719

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

A Phase 2 study testing Ipatasertib and Paclitaxel in people with Breast Neoplasms, run by Genentech, Inc. at 44 sites in 8 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Breast Neoplasms
What is being tested?
Ipatasertib and Paclitaxel
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
124 participants
Where
44 sitesin 8 countries
Study dates
19 Aug 2014to 31 Aug 2019
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

44 sites in 8 countries.

44 sites in 8 countries

United States17 sites
  • Massachusetts General Hospital Cancer Center

    Boston, Massachusetts, 02114

  • Carolinas Healthcare System

    Charlotte, North Carolina, 28208

  • Rush University Medical Center

    Chicago, Illinois, 60612

  • Holycross Medical Group

    Fort Lauderdale, Florida, 33308

  • St Jude Heritage Medical Group

    Fullerton, California, 92835

  • Comprehensive Cancer Centers of Nevada

    Henderson, Nevada, 89014

  • Memorial Healthcare System

    Hollywood, Florida, 33021

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • Northwest Medical Specialties

    Lakewood, Washington, 98499

  • Cedars Sinai Medical Center

    Los Angeles, California, 90048

  • Cancer Care Assoc Med Group

    Los Angeles, California, 90095-1772

  • The WEST CLINIC, P.C.

    Memphis, Tennessee, 38119

  • West Virginia University Hospitals Inc

    Morgantown, West Virginia, 26056

  • Northern Utah Associates

    Ogden, Utah, 84403

  • Hematology Oncology Associates of the Treasure Coast

    Port Saint Lucie, Florida, 34952

  • UCLA Medical Center

    Santa Monica, California, 90404

  • Cancer Center of Kansas

    Wichita, Kansas, 67214-3728

Other trials in United States

South Korea6 sites
  • National Cancer Center

    Goyang-si, 10408

  • Seoul National University Bundang Hospital

    Seongnam-si, 13605

  • Seoul National University Hospital

    Seoul, 03080

  • Severance Hospital, Yonsei University Health System

    Seoul, 03722

  • Asan Medical Center

    Seoul, 05505

  • Korea University Guro Hospital

    Seoul, 08308

Other trials in South Korea

Spain6 sites
  • Hospital Universitari Vall d'Hebron

    Barcelona, 08035

  • Institut Catala d Oncologia Hospital Duran i Reynals

    Barcelona, 08908

  • Complejo Hospitalario de Jaen

    Jaén, 23007

  • MD Anderson Cancer Center

    Madrid, 28033

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

    Madrid, 28050

  • Hospital Virgen del Rocio

    Seville, 41013

Other trials in Spain

France5 sites
  • Institut Bergonié Centre Régional de Lutte Contre Le Cancer de Bordeaux Et Sud Ouest

    Bordeaux, 33076

  • Centre Francois Baclesse

    Caen, 14076

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

    Montpellier, 34298

  • Hopital Saint Louis; Oncologie Medicale

    Paris, 75475

  • Clinique Armoricaine de Radiol

    Saint-Brieuc, 22015

Other trials in France

Taiwan4 sites
  • China Medical University Hospital

    North Dist., 40402

  • Chi Mei Medical Center, Yong kang; Endocrinology

    Tainan, 710

  • National Taiwan University Hospital

    Taipei, 10002

  • Chang Gung Medical Foundation - Linkou; Dept of Surgery

    Taoyuan, 333

Other trials in Taiwan

Italy3 sites
  • Istituto Nazionale dei Tumori; Divisione Oncologia Chirurgica e Ginecologica

    Milan, Lombardy, 20133

  • Istituto Nazionale Tumori Fondazione G. Pascale

    Naples, Campania, 80131

  • Istituto Oncologico Veneto IRCCS Farmacia Ospedaliera

    Padova, Veneto, 35128

Other trials in Italy

Singapore2 sites
  • National University Hospital; National University Cancer Institute, Singapore (NCIS)

    Singapore, 119228

  • National Cancer Centre

    Singapore, 169610

Other trials in Singapore

Belgium1 site
  • Sint Augustinus Wilrijk

    Wilrijk, 2610

Other trials in Belgium

About this study

Official title: 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

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.

Being tested
Ipatasertib, Paclitaxel, Placebo
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IpatasertibDrug

    Also called GDC-0068

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

  • PaclitaxelDrug

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

  • PlaceboDrug

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

Study groups in NCT02162719
Study groupRoleWhat they receive
Ipatasertib + PaclitaxelExperimentalParticipants 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.
Receives: Drug: Ipatasertib; Drug: Paclitaxel
Placebo + PaclitaxelPlacebo 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.
Receives: Drug: Paclitaxel; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Baseline up to 30 days after the last dose of study drug administration (Clinical Cut Off Date: 07 June 2016)

  2. 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.

    Measured: Baseline up to 30 days after the last dose of study drug administration (Clinical Cut Off Date: 07 June 2016)

Secondary outcomes (18)
  1. PFS in Participants With Phosphatidylinositol-4,5-bisphosphate 3-kinase Catalytic Subunit Alpha (PIK3CA)/ Protein Kinase B (AKT1)/ PTEN-altered 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.

    Measured: Baseline up to 30 days after the last dose of study drug administration (Clinical Cut Off Date: 07 June 2016)

  2. Overall Survival (OS)

    OS was defined as the time from the date of randomization to the date of death from any cause.

    Measured: Baseline up to 30 days after the last dose of study drug administration (Clinical Cut Off Date: 31 August 2019)

  3. OS in Participants With PTEN-Low Tumors

    OS was defined as the time from the date of randomization to the date of death from any cause.

    Measured: Baseline up to 30 days after the last dose of study drug administration (Clinical Cut Off Date: 31 August 2019)

  4. OS in Participants With PIK3CA/AKT1/PTEN-altered Tumors

    OS was defined as the time from the date of randomization to the date of death from any cause.

    Measured: Baseline up to 30 days after the last dose of study drug administration (Clinical Cut Off Date: 31 August 2019)

  5. Objective Response Rate (ORR)

    Confirmed tumor ORR in participants with measurable disease at baseline was assessed by the investigator per RECIST, v1.1. Confirmed ORR was defined as the percentage of participants who achieved either a complete response or partial response based on the investigator assessment that was confirmed by a repeat assessment no less than 4 weeks after the criteria for response was first met. Participants for whom no records of post-baseline tumor assessments were reported were counted as non-responders. Complete response (CR): disappearance of all target lesions, any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial response (PR): at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.

    Measured: Baseline up to every 8 weeks until documented disease progression (Clinical Cut Off Date: 07 June 2016)

  6. ORR in Participants With PTEN-Low Tumors

    Confirmed tumor ORR in participants with measurable disease at baseline was assessed by the investigator per RECIST, v1.1. Confirmed ORR was defined as the percentage of participants who achieved either a complete response or partial response based on the investigator assessment that was confirmed by a repeat assessment no less than 4 weeks after the criteria for response was first met. Participants for whom no records of post-baseline tumor assessments were reported were counted as non-responders. Complete response (CR): disappearance of all target lesions, any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial response (PR): at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.

    Measured: Baseline up to every 8 weeks until documented disease progression (Clinical Cut Off Date: 07 June 2016)

  7. ORR in Participants With PIK3CA/AKT1/PTEN-altered Tumors

    Confirmed tumor ORR in subjects with measurable disease at baseline was assessed by the investigator per RECIST, v1.1. Confirmed ORR was defined as the percentage of subjects who achieved either a complete response or partial response based on the investigator assessment that was confirmed by a repeat assessment no less than 4 weeks after the criteria for response was first met. Subjects for whom no records of post-baseline tumor assessments were reported were counted as non-responders. Complete response (CR): disappearance of all target lesions, any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial response (PR): at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.

    Measured: Baseline up to every 8 weeks until documented disease progression (Clinical Cut Off Date: 07 June 2016)

  8. Duration of Response

    Duration of objective response in subjects with measurable disease at baseline was defined as the time from first observation of an objective tumor response until first observation of disease progression, as assessed by the investigator per modified RECIST, v1.1.

    Measured: Baseline up to every 8 weeks until documented disease progression (Clinical Cut Off Date: 07 June 2016)

  9. Duration of Response in Participants With PTEN-Low Tumors

    Duration of objective response in subjects with measurable disease at baseline was defined as the time from first observation of an objective tumor response until first observation of disease progression, as assessed by the investigator per modified RECIST, v1.1.

    Measured: Baseline up to every 8 weeks until documented disease progression (Clinical Cut Off Date: 07 June 2016)

  10. Duration of Response in Participants With PIK3CA/AKT1/PTEN-altered Tumors

    Duration of objective response in participants with measurable disease at baseline was defined as the time from first observation of an objective tumor response until first observation of disease progression, as assessed by the investigator per modified RECIST, v1.1.

    Measured: Baseline up to every 8 weeks until documented disease progression (Clinical Cut Off Date: 07 June 2016)

  11. Time to Disease Progression

    Time to disease progression 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.

    Measured: Baseline up to every 8 weeks until documented disease progression (Clinical Cut Off Date: 07 June 2016)

  12. Time to Disease Progression in Participants With PTEN-Low Tumors

    Time to disease progression 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.

    Measured: Baseline up to every 8 weeks until documented disease progression (Clinical Cut Off Date: 07 June 2016)

  13. Time to Disease Progression in Participants With PIK3CA/AKT1/PTEN-altered Tumors

    Time to disease progression 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.

    Measured: Baseline up to every 8 weeks until documented disease progression (Clinical Cut Off Date: 07 June 2016)

  14. Safety: Percentage of Participants With Adverse Events

    An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.

    Measured: Baseline up to 30 days after the last dose of study drug or until initiation of another anti-cancer therapy, whichever occurs first (up to 3 years, 3 months)

  15. Pharmacokinetic Endpoint: Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero to 24 Hours (AUC0-24h) of Ipatasertib

    PK parameters were not calculated due to sparse PK sampling.

    Measured: Cycle 1 Day 1, Cycle 1 Day 8

  16. Pharmacokinetic Endpoint: Apparent Clearance Following Oral Dosing (CL/F) of Ipatasertib

    PK parameters were not calculated due to sparse PK sampling.

    Measured: Cycle 1 Day 1, Cycle 1 Day 8

  17. Patient Reported Outcome (PRO) Measure: Mean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item (EORTC QLQ-C30) Score

    EORTC QLQ-C30 included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting), single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea, financial difficulties). Most questions used 4-point scale (1=Not at all to 4=Very much; 2 questions used 7-point scale [1=very poor to 7=Excellent]). Scores averaged, transformed to 0-100 scale; a higher score=better level of functioning. For symptom scale scores, higher level=severe level of symptoms. "A change of at least 10 points from baseline is considered clinically meaningful (Osoba D, Rodrigues G, Myles J, et al. Interpreting the significance of changes in health-related quality of life score. J Clin Oncol 1998;16:139-44). PRO measures were analyzed from baseline up to cycle 5. Scores from later timepoints were not analyzed due to attrition (in both arms, fewer than 50% of participants remained on treatment beyond cycle 5).

    Measured: Baseline (Cycle 1 Day 1) up to Cycle 5 Day 1

  18. PRO Measure: Percentage of Participants With Improved, Worsened, or Remained Stable for Bothersome Side Effects of Treatment Measured by the Scales of the EORTC QLQ-C30

    Subjects reporting >/= 10-point increase compared to baseline (Cycle 1 Day 1) were considered "improved", those reporting <10-point difference were considered "remained stable", and those reporting >/=10-point decrease were considered "worsened". A change of at least 10 points from baseline is considered clinically meaningful (Osoba D, Rodrigues G, Myles J, et al. Interpreting the significance of changes in health-related quality of life score. J Clin Oncol 1998;16:139-44). Patient reported outcome measures were analyzed from baseline up to and including cycle 5. Scores from later timepoints were not analyzed due to attrition (in both arms, fewer than 50% of participants remained on treatment beyond cycle 5).

    Measured: Baseline (Cycle 1 Day 1) up to Cycle 5 Day 1

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Jun 2014 (estimated)
  2. Study start19 Aug 2014
  3. Primary completion7 Jun 2016
  4. Study completion31 Aug 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
124 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02162719
Sponsor's protocol ID
GO29227
Other IDs
2014-000469-35, 2014
Acronym
LOTUS
Status last verified
Feb 2021
First submitted
11 Jun 2014
Last updated
10 Mar 2021
Individual data sharing
Yes: 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).

Publications

  • 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.

    PubMed 28800861

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ipatasertib and Paclitaxel in people with Breast Neoplasms, run by Genentech, Inc. at 44 sites in 8 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 44 sites in United States, South Korea, Spain, France, Taiwan and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 Jan 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression Free Survival (PFS) (time frame: Baseline up to 30 days after the last dose of study drug administration (Clinical Cut Off Date: 07 June 2016)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02162719, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Mar 2021.

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