Trial Review

Please note the ANZCTR will be unattended from Friday 20 December 2024 for the holidays. The Registry will re-open on Tuesday 7 January 2025. Submissions and updates will not be processed during that time.

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03337724




Registration number
NCT03337724
Ethics application status
Date submitted
7/11/2017
Date registered
9/11/2017
Date last updated
12/03/2024

Titles & IDs
Public title
A Study of Ipatasertib in Combination With Paclitaxel as a Treatment for Participants With PIK3CA/AKT1/PTEN-Altered, Locally Advanced or Metastatic, Triple-Negative Breast Cancer or Hormone Receptor-Positive, HER2-Negative Breast Cancer
Scientific title
A Double-Blind, Placebo-Controlled, Randomized Phase III Study of Ipatasertib in Combination With Paclitaxel as a Treatment for Patients With PIK3CA/AKT1/PTEN-Altered, Locally Advanced or Metastatic, Triple-Negative Breast Cancer or Hormone Receptor-Positive, HER2-Negative Breast Cancer
Secondary ID [1] 0 0
2017-001548-36
Secondary ID [2] 0 0
CO40016
Universal Trial Number (UTN)
Trial acronym
IPATunity130
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Ipatasertib
Treatment: Drugs - Paclitaxel
Treatment: Drugs - Placebo

Experimental: Ipatasertib + Paclitaxel -

Experimental: Placebo + Paclitaxel -


Treatment: Drugs: Ipatasertib
Ipatasertib, 400 milligrams (mg), administered orally once a day (QD) on Days 1-21 of each 28-day cycle until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.

Treatment: Drugs: Paclitaxel
Paclitaxel, 80 mg/square meter (m\^2), administered intravenously (IV) on Days 1, 8, and 15 of each 28-day cycle until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.

Treatment: Drugs: Placebo
Matching placebo, administered orally QD on Days 1-21 of each 28-day cycle until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Cohort A: Progression-Free Survival (PFS)
Timepoint [1] 0 0
From randomization up to 27 months
Primary outcome [2] 0 0
Cohort B: PFS
Timepoint [2] 0 0
From randomization up to 24.4 months
Primary outcome [3] 0 0
Cohort C: PFS
Timepoint [3] 0 0
From enrollment up to 31 months
Secondary outcome [1] 0 0
Cohort A and B: Objective Response Rate (ORR)
Timepoint [1] 0 0
From randomization up to 27 months for Cohort A and up to 24.4 months for Cohort B
Secondary outcome [2] 0 0
Cohort C: ORR
Timepoint [2] 0 0
From enrollment up to 31 months
Secondary outcome [3] 0 0
Cohort A and B: Duration of Response (DOR)
Timepoint [3] 0 0
From randomization up to 27 months for Cohort A and up to 24.4 months for Cohort B
Secondary outcome [4] 0 0
Cohort C: DOR
Timepoint [4] 0 0
From enrollment up to 31 months
Secondary outcome [5] 0 0
Cohort A and B: Clinical Benefit Rate (CBR)
Timepoint [5] 0 0
From randomization up to 27 months for Cohort A and up to 24.4 months for Cohort B
Secondary outcome [6] 0 0
Cohort C: CBR
Timepoint [6] 0 0
From enrollment up to 31 months
Secondary outcome [7] 0 0
Overall Survival (OS)
Timepoint [7] 0 0
From randomization/ enrollment (Cohort C) up to death from any cause, up to 45 months for Cohort A, up to 46 months for Cohort B and up to 31 months for Cohort C
Secondary outcome [8] 0 0
Cohort A and B: Change From Baseline in Global Health Status (GHS)/Health-Related Quality of Life (HRQoL) Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Timepoint [8] 0 0
Baseline, Day 1 of Cycles 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 and 24 (cycle length=28 days)
Secondary outcome [9] 0 0
Cohort C: Change From Baseline in GHS/HRQoL Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30
Timepoint [9] 0 0
Baseline, Day 1 of Cycles 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, and 44 (cycle length=28 days)
Secondary outcome [10] 0 0
Cohort B: Time to Deterioration (TTD) in Pain
Timepoint [10] 0 0
Baseline up to 24.4 months
Secondary outcome [11] 0 0
Number of Participants With Adverse Events (AEs)
Timepoint [11] 0 0
Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
Secondary outcome [12] 0 0
Number of Participants With at Least One Adverse Events of Special Interest (AESI)
Timepoint [12] 0 0
Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
Secondary outcome [13] 0 0
Cohorts A and B:Plasma Concentration of Ipatasertib
Timepoint [13] 0 0
Days 1 and 15 of Cycle 1: 1 to 3 hours post dose, and on Day 15 of Cycle 3: 2 to 4 hours post dose (cycle length= 28 days)
Secondary outcome [14] 0 0
Cohort C: Plasma Concentration of Ipatasertib
Timepoint [14] 0 0
Days 1 and 15 of Cycle 1: 1 to 3 hours post dose, and on Day 15 of Cycle 3: 2 to 4 hours post dose (cycle length= 28 days)
Secondary outcome [15] 0 0
Cohorts A and B: Plasma Concentration of G-037720
Timepoint [15] 0 0
Days 1 and 15 of Cycle 1: 1 to 3 hours post dose, and on Day 15 of Cycle 3: 2 to 4 hours post dose (cycle length= 28 days )
Secondary outcome [16] 0 0
Cohort C: Plasma Concentration of G-037720
Timepoint [16] 0 0
Days 1 and 15 of Cycle 1: 1 to 3 hours post dose, and on Day 15 of Cycle 3: 2 to 4 hours post dose (cycle length= 28 days )
Secondary outcome [17] 0 0
Cohort C: 1-year Event-free PFS Rate
Timepoint [17] 0 0
From enrollment until the occurrence of disease progression or death from any cause, whichever occurred earlier, up to 1 year
Secondary outcome [18] 0 0
Cohort C: 1-year Event-free OS Rate
Timepoint [18] 0 0
From enrollment up to death from any cause, up to 1 year
Secondary outcome [19] 0 0
Cohort C: Serum Concentration of Atezolizumab
Timepoint [19] 0 0
Day 1 of Cycle 1: 30 minutes post dose, predose on Day 15 of Cycle 1 and predose on Day 1 of Cycles 2, 3, 4, 8, 12 and 16 (cycle length=28 days)
Secondary outcome [20] 0 0
Cohort C: Number of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab
Timepoint [20] 0 0
Up to 45.5 months

Eligibility
Key inclusion criteria
* Women or men aged =>18 years with histologically documented triple-negative breast cancer (TNBC) or HR+/HER2- adenocarcinoma of the breast that is locally advanced or metastatic and is not amenable to resection with curative intent
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
* Adequate hematologic and organ function within 14 days prior to treatment initiation
* Histologically documented TNBC or HR+/HER2- adenocarcinoma of the breast that is locally advanced or metastatic and is not amenable to resection with curative intent
* Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
* Eligible for taxane monotherapy, as per local investigator assessment (e.g., absence of rapid clinical progression, life-threatening visceral metastases, or the need for rapid symptom and/or disease control which may require combination chemotherapy)
* HR+/HER2- breast cancer that is not considered appropriate for endocrine-based therapy and meets one of the following: patient has recurrent disease <=5 years of being on adjuvant endocrine therapy or if patient with de novo metastatic disease have progressed within 6 months of being on first line endocrine therapy.
* Consent to submit a formalin-fixed, paraffin-embedded tumor (FFPE) tissue block or freshly cut unstained, serial tumor slides from the most recently collected tumor tissue for central molecular analysis
* Confirmation of biomarker eligibility using an appropriately validated molecular assay at a diagnostic laboratory, Clinically Laboratory Improvement Amendments (CLIA) or equivalently accredited i.e., valid results from either central testing or local testing of tumor tissue or blood demonstrating PIK3CA/AKT1/PTEN-altered status
* For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception and agreement to refrain from donating eggs
* For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods and agreement to refrain from donating sperm
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Treatment with approved or investigational cancer therapy within 14 days prior to treatment initiation
* Any previous chemotherapy for inoperable locally advanced or metastatic TNBC or HR+/HER2- adenocarcinoma of the breast (patients receiving neo/adjuvant chemotherapy eligible provided they have at least a 12 month disease-free interval)
* History of or known presence of brain or spinal cord metastases
* Malignancies other than breast cancer within 5 years prior to treatment initiation (except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or Stage I uterine cancer)
* Prior treatment with an Akt inhibitor (prior PI3K or mTOR inhibitors are allowed)
* History of malabsorption syndrome or other condition that would interfere with enteral absorption or results in the inability or unwillingness to swallow pills
* Active infection requiring systemic anti-microbial treatment (including antibiotics, anti-fungals, and anti-viral agents)
* Known human immunodeficiency virus (HIV) infection
* Known clinically significant history of liver disease consistent with Child-Pugh Class B or C, including active viral or other hepatitis, current drug or alcohol abuse, or cirrhosis
* Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to initiation of treatment (or anticipated need during study)
* Pregnant or breastfeeding, or intending to become pregnant during the study
* Clinically significant cardiac dysfunction (including NYHA Class II/III/IV heart failure, left ventricular ejection fraction [LVEF] <50%, active ventricular arrhythmia requiring medication, history of myocardial infarction within 6 months of treatment initiation, clinically significant electrocardiogram [ECG] abnormalities).
* Need for chronic corticosteroid therapy of >=10 mg of prednisone per day or an equivalent dose of other anti-inflammatory corticosteroids or immunosuppressants for a chronic disease
* Unresolved, clinically significant toxicity from prior therapy, except for alopecia and Grade 1 peripheral neuropathy
* Uncontrolled clinical symptoms including pleural effusion, pericardial effusion, or ascites, tumor-related pain, hypercalcemia (or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy)
* History of Type I or Type II diabetes mellitus requiring insulin
* Grade >=2 uncontrolled or untreated hypercholesterolemia or hypertriglyceridemia
* History of or active inflammatory bowel disease or active bowel inflammation
* Clinically significant lung disease (including pneumonitis, interstitial lung disease, idiopathic pulmonary fibrosis, cystic fibrosis, active infection/ history of opportunistic infections)
* Treatment with strong CYP3A inhibitors or strong CYP3A inducers within 2 weeks or 5 drug-elimination half-lives, whichever is longer, prior to initiation of treatment
* Grade >=2 peripheral neuropathy

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
6/01/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
4/01/2023
Sample size
Target
Accrual to date
Final
579
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
Chris O'Brien Lifehouse - Camperdown
Recruitment hospital [2] 0 0
Calvary Mater Newcastle; Medical Oncology - Waratah
Recruitment hospital [3] 0 0
Westmead Hospital; Medical Oncology - Wentworthville
Recruitment hospital [4] 0 0
Mater Hospital; Cancer Services - South Brisbane
Recruitment hospital [5] 0 0
Cabrini Medical Centre; Oncology - Malvern
Recruitment hospital [6] 0 0
Fiona Stanley Hospital; FSH Cancer Centre Clinical Trials Unit - Bull Creek
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2298 - Waratah
Recruitment postcode(s) [3] 0 0
2145 - Wentworthville
Recruitment postcode(s) [4] 0 0
4101 - South Brisbane
Recruitment postcode(s) [5] 0 0
3144 - Malvern
Recruitment postcode(s) [6] 0 0
6149 - Bull Creek
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Maryland
Country [4] 0 0
United States of America
State/province [4] 0 0
New York
Country [5] 0 0
United States of America
State/province [5] 0 0
Tennessee
Country [6] 0 0
United States of America
State/province [6] 0 0
Texas
Country [7] 0 0
Argentina
State/province [7] 0 0
Buenos Aires
Country [8] 0 0
Argentina
State/province [8] 0 0
Rosario
Country [9] 0 0
Belgium
State/province [9] 0 0
Bruxelles
Country [10] 0 0
Belgium
State/province [10] 0 0
Charleroi
Country [11] 0 0
Belgium
State/province [11] 0 0
Leuven
Country [12] 0 0
Brazil
State/province [12] 0 0
BA
Country [13] 0 0
Brazil
State/province [13] 0 0
GO
Country [14] 0 0
Brazil
State/province [14] 0 0
PR
Country [15] 0 0
Brazil
State/province [15] 0 0
RJ
Country [16] 0 0
Brazil
State/province [16] 0 0
RS
Country [17] 0 0
Brazil
State/province [17] 0 0
SP
Country [18] 0 0
Canada
State/province [18] 0 0
British Columbia
Country [19] 0 0
Canada
State/province [19] 0 0
Quebec
Country [20] 0 0
Chile
State/province [20] 0 0
Temuco
Country [21] 0 0
Costa Rica
State/province [21] 0 0
San José
Country [22] 0 0
Czechia
State/province [22] 0 0
Brno
Country [23] 0 0
Czechia
State/province [23] 0 0
Olomouc
Country [24] 0 0
France
State/province [24] 0 0
Besançon Cedex
Country [25] 0 0
France
State/province [25] 0 0
Bordeaux
Country [26] 0 0
France
State/province [26] 0 0
Dijon
Country [27] 0 0
France
State/province [27] 0 0
Montpellier cedex 5
Country [28] 0 0
France
State/province [28] 0 0
Nantes
Country [29] 0 0
France
State/province [29] 0 0
Paris
Country [30] 0 0
France
State/province [30] 0 0
Reims CEDEX
Country [31] 0 0
Germany
State/province [31] 0 0
Berlin
Country [32] 0 0
Germany
State/province [32] 0 0
Freiburg
Country [33] 0 0
Germany
State/province [33] 0 0
Hamburg
Country [34] 0 0
Germany
State/province [34] 0 0
Homburg/Saar
Country [35] 0 0
Germany
State/province [35] 0 0
Köln
Country [36] 0 0
Germany
State/province [36] 0 0
Langen
Country [37] 0 0
Germany
State/province [37] 0 0
Minden
Country [38] 0 0
Germany
State/province [38] 0 0
Recklinghausen
Country [39] 0 0
Germany
State/province [39] 0 0
Rostock
Country [40] 0 0
Germany
State/province [40] 0 0
Würzburg
Country [41] 0 0
Greece
State/province [41] 0 0
Athens
Country [42] 0 0
Greece
State/province [42] 0 0
Thessaloniki
Country [43] 0 0
Hungary
State/province [43] 0 0
Budapest
Country [44] 0 0
Hungary
State/province [44] 0 0
Miskolc
Country [45] 0 0
Hungary
State/province [45] 0 0
Szeged
Country [46] 0 0
Hungary
State/province [46] 0 0
Szolnok
Country [47] 0 0
Hungary
State/province [47] 0 0
Zalaegerszeg
Country [48] 0 0
India
State/province [48] 0 0
Delhi
Country [49] 0 0
Italy
State/province [49] 0 0
Campania
Country [50] 0 0
Italy
State/province [50] 0 0
Emilia-Romagna
Country [51] 0 0
Italy
State/province [51] 0 0
Friuli-Venezia Giulia
Country [52] 0 0
Italy
State/province [52] 0 0
Toscana
Country [53] 0 0
Italy
State/province [53] 0 0
Veneto
Country [54] 0 0
Japan
State/province [54] 0 0
Aichi
Country [55] 0 0
Japan
State/province [55] 0 0
Chiba
Country [56] 0 0
Japan
State/province [56] 0 0
Fukuoka
Country [57] 0 0
Japan
State/province [57] 0 0
Fukushima
Country [58] 0 0
Japan
State/province [58] 0 0
Hyogo
Country [59] 0 0
Japan
State/province [59] 0 0
Kanagawa
Country [60] 0 0
Japan
State/province [60] 0 0
Kumamoto
Country [61] 0 0
Japan
State/province [61] 0 0
Niigata
Country [62] 0 0
Japan
State/province [62] 0 0
Okayama
Country [63] 0 0
Japan
State/province [63] 0 0
Osaka
Country [64] 0 0
Japan
State/province [64] 0 0
Saitama
Country [65] 0 0
Japan
State/province [65] 0 0
Shizuoka
Country [66] 0 0
Japan
State/province [66] 0 0
Tokyo
Country [67] 0 0
Korea, Republic of
State/province [67] 0 0
Goyang-si
Country [68] 0 0
Korea, Republic of
State/province [68] 0 0
Incheon
Country [69] 0 0
Korea, Republic of
State/province [69] 0 0
Seongnam-si
Country [70] 0 0
Korea, Republic of
State/province [70] 0 0
Seoul
Country [71] 0 0
Mexico
State/province [71] 0 0
Mexico CITY (federal District)
Country [72] 0 0
Mexico
State/province [72] 0 0
Nuevo LEON
Country [73] 0 0
Mexico
State/province [73] 0 0
Yucatan
Country [74] 0 0
Mexico
State/province [74] 0 0
Mexico City
Country [75] 0 0
North Macedonia
State/province [75] 0 0
Bitola
Country [76] 0 0
North Macedonia
State/province [76] 0 0
Skopje
Country [77] 0 0
Peru
State/province [77] 0 0
Arequipa
Country [78] 0 0
Peru
State/province [78] 0 0
Callao
Country [79] 0 0
Peru
State/province [79] 0 0
Lima
Country [80] 0 0
Peru
State/province [80] 0 0
San Isidro
Country [81] 0 0
Peru
State/province [81] 0 0
Trujillo
Country [82] 0 0
Poland
State/province [82] 0 0
?ód?
Country [83] 0 0
Poland
State/province [83] 0 0
Gliwice
Country [84] 0 0
Poland
State/province [84] 0 0
Warszawa
Country [85] 0 0
Russian Federation
State/province [85] 0 0
Arhangelsk
Country [86] 0 0
Russian Federation
State/province [86] 0 0
Moskovskaja Oblast
Country [87] 0 0
Russian Federation
State/province [87] 0 0
Rostov
Country [88] 0 0
Russian Federation
State/province [88] 0 0
Sankt Petersburg
Country [89] 0 0
Russian Federation
State/province [89] 0 0
Tatarstan
Country [90] 0 0
Russian Federation
State/province [90] 0 0
Ivanovo
Country [91] 0 0
Russian Federation
State/province [91] 0 0
Kaluga
Country [92] 0 0
Singapore
State/province [92] 0 0
Singapore
Country [93] 0 0
Slovenia
State/province [93] 0 0
Ljubljana
Country [94] 0 0
South Africa
State/province [94] 0 0
Johannesburg
Country [95] 0 0
Spain
State/province [95] 0 0
Castellon
Country [96] 0 0
Spain
State/province [96] 0 0
Cordoba
Country [97] 0 0
Spain
State/province [97] 0 0
LA Coruña
Country [98] 0 0
Spain
State/province [98] 0 0
Madrid
Country [99] 0 0
Spain
State/province [99] 0 0
Barcelona
Country [100] 0 0
Spain
State/province [100] 0 0
Guipuzcoa
Country [101] 0 0
Spain
State/province [101] 0 0
Sevilla
Country [102] 0 0
Spain
State/province [102] 0 0
Valencia
Country [103] 0 0
Taiwan
State/province [103] 0 0
Liuying Township
Country [104] 0 0
Taiwan
State/province [104] 0 0
Taipei City
Country [105] 0 0
Taiwan
State/province [105] 0 0
Taipei
Country [106] 0 0
Turkey
State/province [106] 0 0
Ankara
Country [107] 0 0
Turkey
State/province [107] 0 0
Diyarbakir
Country [108] 0 0
Turkey
State/province [108] 0 0
Istanbul
Country [109] 0 0
Turkey
State/province [109] 0 0
Izmir
Country [110] 0 0
Turkey
State/province [110] 0 0
Sakarya
Country [111] 0 0
Ukraine
State/province [111] 0 0
Dnipropetrovsk
Country [112] 0 0
Ukraine
State/province [112] 0 0
Kiev
Country [113] 0 0
Ukraine
State/province [113] 0 0
Lviv
Country [114] 0 0
United Kingdom
State/province [114] 0 0
Cardiff
Country [115] 0 0
United Kingdom
State/province [115] 0 0
Coventry
Country [116] 0 0
United Kingdom
State/province [116] 0 0
Glasgow
Country [117] 0 0
United Kingdom
State/province [117] 0 0
London
Country [118] 0 0
United Kingdom
State/province [118] 0 0
Plymouth
Country [119] 0 0
United Kingdom
State/province [119] 0 0
Stoke-on-Trent
Country [120] 0 0
United Kingdom
State/province [120] 0 0
Sutton

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT03337724