Clinical trial NCT02162719: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Neoplasms
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2014-06-13
Enrollment: 124
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: Baseline up to 30 days after the last dose of study drug administration (Clinical Cut Off Date: 07 June 2016)
measure: PFS in Participants With Phosphatase and Tensin Homolog (PTEN)-Low Tumors
timeFrame: Baseline up to 30 days after the last dose of study drug administration (Clinical Cut Off Date: 07 June 2016)
Secondary outcomes:
measure: PFS in Participants With Phosphatidylinositol-4,5-bisphosphate 3-kinase Catalytic Subunit Alpha (PIK3CA)/ Protein Kinase B (AKT1)/ PTEN-altered Tumors
timeFrame: Baseline up to 30 days after the last dose of study drug administration (Clinical Cut Off Date: 07 June 2016)
measure: Overall Survival (OS)
timeFrame: Baseline up to 30 days after the last dose of study drug administration (Clinical Cut Off Date: 31 August 2019)
measure: OS in Participants With PTEN-Low Tumors
timeFrame: Baseline up to 30 days after the last dose of study drug administration (Clinical Cut Off Date: 31 August 2019)
measure: OS in Participants With PIK3CA/AKT1/PTEN-altered Tumors
timeFrame: Baseline up to 30 days after the last dose of study drug administration (Clinical Cut Off Date: 31 August 2019)
measure: Objective Response Rate (ORR)
timeFrame: Baseline up to every 8 weeks until documented disease progression (Clinical Cut Off Date: 07 June 2016)
measure: ORR in Participants With PTEN-Low Tumors
timeFrame: Baseline up to every 8 weeks until documented disease progression (Clinical Cut Off Date: 07 June 2016)
measure: ORR in Participants With PIK3CA/AKT1/PTEN-altered Tumors
timeFrame: Baseline up to every 8 weeks until documented disease progression (Clinical Cut Off Date: 07 June 2016)
measure: Duration of Response
timeFrame: Baseline up to every 8 weeks until documented disease progression (Clinical Cut Off Date: 07 June 2016)
measure: Duration of Response in Participants With PTEN-Low Tumors
timeFrame: Baseline up to every 8 weeks until documented disease progression (Clinical Cut Off Date: 07 June 2016)
measure: Duration of Response in Participants With PIK3CA/AKT1/PTEN-altered Tumors
timeFrame: Baseline up to every 8 weeks until documented disease progression (Clinical Cut Off Date: 07 June 2016)
measure: Time to Disease Progression
timeFrame: Baseline up to every 8 weeks until documented disease progression (Clinical Cut Off Date: 07 June 2016)
measure: Time to Disease Progression in Participants With PTEN-Low Tumors
timeFrame: Baseline up to every 8 weeks until documented disease progression (Clinical Cut Off Date: 07 June 2016)
measure: Time to Disease Progression in Participants With PIK3CA/AKT1/PTEN-altered Tumors
timeFrame: Baseline up to every 8 weeks until documented disease progression (Clinical Cut Off Date: 07 June 2016)
measure: Safety: Percentage of Participants With Adverse Events
timeFrame: 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)
measure: Pharmacokinetic Endpoint: Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero to 24 Hours (AUC0-24h) of Ipatasertib
timeFrame: Cycle 1 Day 1, Cycle 1 Day 8
measure: Pharmacokinetic Endpoint: Apparent Clearance Following Oral Dosing (CL/F) of Ipatasertib
timeFrame: Cycle 1 Day 1, Cycle 1 Day 8
measure: 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
timeFrame: Baseline (Cycle 1 Day 1) up to Cycle 5 Day 1
measure: 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
timeFrame: Baseline (Cycle 1 Day 1) up to Cycle 5 Day 1
Other outcomes:
Locations:
city: Fullerton
country: United States
facility: St Jude Heritage Medical Group
state: California
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center
state: California
city: Los Angeles
country: United States
facility: Cancer Care Assoc Med Group
state: California
city: Santa Monica
country: United States
facility: UCLA Medical Center
state: California
city: Fort Lauderdale
country: United States
facility: Holycross Medical Group
state: Florida
city: Hollywood
country: United States
facility: Memorial Healthcare System
state: Florida
city: Port Saint Lucie
country: United States
facility: Hematology Oncology Associates of the Treasure Coast
state: Florida
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Wichita
country: United States
facility: Cancer Center of Kansas
state: Kansas
city: Boston
country: United States
facility: Massachusetts General Hospital Cancer Center
state: Massachusetts
city: Henderson
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Charlotte
country: United States
facility: Carolinas Healthcare System
state: North Carolina
city: Memphis
country: United States
facility: The WEST CLINIC, P.C.
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Ogden
country: United States
facility: Northern Utah Associates
state: Utah
city: Lakewood
country: United States
facility: Northwest Medical Specialties
state: Washington
city: Morgantown
country: United States
facility: West Virginia University Hospitals Inc
state: West Virginia
city: Wilrijk
country: Belgium
facility: Sint Augustinus Wilrijk
city: Bordeaux
country: France
facility: Institut Bergonié Centre Régional de Lutte Contre Le Cancer de Bordeaux Et Sud Ouest
city: Caen
country: France
facility: Centre Francois Baclesse
city: Montpellier
country: France
facility: Centre Régional de Lutte Contre Le Cancer Val D'aurelle Paul Lamarque
city: Paris
country: France
facility: Hopital Saint Louis; Oncologie Medicale
city: Saint Brieuc
country: France
facility: Clinique Armoricaine de Radiol
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori Fondazione G. Pascale
state: Campania
city: Milano
country: Italy
facility: Istituto Nazionale dei Tumori; Divisione Oncologia Chirurgica e Ginecologica
state: Lombardia
city: Padova
country: Italy
facility: Istituto Oncologico Veneto IRCCS Farmacia Ospedaliera
state: Veneto
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
city: Singapore
country: Singapore
facility: National University Hospital; National University Cancer Institute, Singapore (NCIS)
city: Singapore
country: Singapore
facility: National Cancer Centre
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Barcelona
country: Spain
facility: Institut Catala d Oncologia Hospital Duran i Reynals
city: Jaen
country: Spain
facility: Complejo Hospitalario de Jaen
city: Madrid
country: Spain
facility: MD Anderson Cancer Center
city: Madrid
country: Spain
facility: HOSPITAL DE MADRID NORTE SANCHINARRO- CENTRO INTEGRAL ONCOLOGICO CLARA CAMPAL; Servicio de Farmacia
city: Sevilla
country: Spain
facility: Hospital Virgen del Rocio
city: North Dist.
country: Taiwan
facility: China Medical University Hospital
city: Tainan
country: Taiwan
facility: Chi Mei Medical Center, Yong kang; Endocrinology
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taoyuan
country: Taiwan
facility: Chang Gung Medical Foundation - Linkou; Dept of Surgery
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.