Trial Review

Technical difficulties have been reported by some users of the search function and is being investigated by technical staff. Thank you for your patience and apologies for any inconvenience caused.

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/NCT04191499




Registration number
NCT04191499
Ethics application status
Date submitted
2/12/2019
Date registered
9/12/2019
Date last updated
26/06/2024

Titles & IDs
Public title
A Study Evaluating the Efficacy and Safety of Inavolisib + Palbociclib + Fulvestrant vs Placebo + Palbociclib + Fulvestrant in Patients With PIK3CA-Mutant, Hormone Receptor-Positive, Her2-Negative, Locally Advanced or Metastatic Breast Cancer
Scientific title
A Phase III, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of Inavolisib Plus Palbociclib and Fulvestrant Versus Placebo Plus Palbociclib and Fulvestrant in Patients With PIK3CA-Mutant, Hormone Receptor-Positive, Her2-Negative, Locally Advanced or Metastatic Breast Cancer
Secondary ID [1] 0 0
2019-002455-42
Secondary ID [2] 0 0
WO41554
Universal Trial Number (UTN)
Trial acronym
INAVO120
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 - Inavolisib
Treatment: Drugs - Placebo
Treatment: Drugs - Palbociclib
Treatment: Drugs - Fulvestrant

Experimental: Inavolisib + Palbociclib + Fulvestrant - Participants will receive inavolisib, palbociclib, and fulvestrant.

Placebo comparator: Placebo + Palbociclib + Fulvestrant - Participants will receive placebo, palbociclib, and fulvestrant.


Treatment: Drugs: Inavolisib
Participants will receive oral inavolisib on Days 1-28 of each 28-day cycle.

Treatment: Drugs: Placebo
Participants will receive oral placebo on Days 1-28 of each 28-day cycle.

Treatment: Drugs: Palbociclib
Participants will receive oral palbociclib on Days 1-21 of each 28-day cycle.

Treatment: Drugs: Fulvestrant
Participants will receive intramuscular (IM) fulvestrant approximately every 4 weeks.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-Free Survival (PFS)
Timepoint [1] 0 0
From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to 6 years)
Secondary outcome [1] 0 0
Objective Response Rate (ORR)
Timepoint [1] 0 0
Up to 6 years
Secondary outcome [2] 0 0
Best Overall Response Rate (BOR)
Timepoint [2] 0 0
Up to 6 years
Secondary outcome [3] 0 0
Duration of Response (DOR)
Timepoint [3] 0 0
From the first occurrence of a CR or PR to the first occurrence of disease progression or death from any cause, whichever occurs first (up to 6 years)
Secondary outcome [4] 0 0
Clinical Benefit Rate (CBR)
Timepoint [4] 0 0
Up to 6 years
Secondary outcome [5] 0 0
Overall Survival (OS)
Timepoint [5] 0 0
From randomization to death from any cause (up to 6 years)
Secondary outcome [6] 0 0
Time to Deterioration (TTD) in Pain
Timepoint [6] 0 0
Treatment: Day 1 of Cycles 1-3, then Day 1 of every other cycle until treatment discontinuation. Post-treatment: Every 8 weeks for 2 years, then every 12 weeks thereafter, to end of study (up to 6 years)(Cycle length = 28 days)
Secondary outcome [7] 0 0
TTD in Physical Function
Timepoint [7] 0 0
Treatment: Day 1 of Cycles 1-3, then Day 1 of every other cycle until treatment discontinuation. Post-treatment: Every 8 weeks for 2 years, then every 12 weeks thereafter, to end of study (up to 6 years)(Cycle length = 28 days)
Secondary outcome [8] 0 0
TTD in Role Function
Timepoint [8] 0 0
Treatment: Day 1 of Cycles 1-3, then Day 1 of every other cycle until treatment discontinuation. Post-treatment: Every 8 weeks for 2 years, then every 12 weeks thereafter, to end of study (up to 6 years)(Cycle length = 28 days)
Secondary outcome [9] 0 0
TTD in Global Health Status
Timepoint [9] 0 0
Treatment: Day 1 of Cycles 1-3, then Day 1 of every other cycle until treatment discontinuation. Post-treatment: Every 8 weeks for 2 years, then every 12 weeks thereafter, to end of study (up to 6 years)(Cycle length = 28 days)
Secondary outcome [10] 0 0
Percentage of Participants with Adverse Events
Timepoint [10] 0 0
From randomization through the end of study (up to 6 years)
Secondary outcome [11] 0 0
Plasma Concentration of Inavolisib
Timepoint [11] 0 0
At pre-defined intervals from baseline to the end of study (up to 6 years)
Secondary outcome [12] 0 0
Plasma Concentration of Palbociclib
Timepoint [12] 0 0
At pre-defined intervals from baseline to the end of study (up to 6 years)
Secondary outcome [13] 0 0
Plasma Concentration of Fulvestrant
Timepoint [13] 0 0
At pre-defined intervals from baseline to the end of study (up to 6 years)

Eligibility
Key inclusion criteria
Inclusion Criteria

* Confirmed diagnosis of HR+/HER2- breast cancer
* Metastatic or locally advanced disease not amenable to curative therapy
* Progression of disease during adjuvant endocrine treatment or within 12 months of completing adjuvant endocrine therapy with an aromatase inhibitor or tamoxifen
* Receiving LHRH agonist therapy for at least 2 weeks prior to Day 1 of Cycle 1 if pre/peri-menopausal
* Confirmation of biomarker eligibility (detection of specified mutation(s) of PIK3CA via specified test)
* Consent to provide fresh or archival tumor tissue specimen
* Measurable disease per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1); evaluable "bone-only" disease is not eligible; "bone-only" disease with at least one measurable, soft-tissue component, even if considered disease that is limited to bone but has lytic or mixed lytic/blastic lesions and at least one measurable soft-tissue component per RECIST v1.1 may be eligible
* Eastern Cooperative Oncology Group Performance Status of 0 or 1
* Life expectancy of > 6 months
* Adequate hematologic and organ function within 14 days prior to initiation of study treatment
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria

* Metaplastic breast cancer
* Any history of leptomeningeal disease or carcinomatous meningitis
* Any prior systemic therapy for metastatic breast cancer
* Prior treatment with fulvestrant or any selective estrogen-receptor degrader, with the exception of participants that have received fulvestrant or any selective estrogen-receptor degrader as part of neoadjuvant therapy only and with treatment duration of no longer than 6 months
* Prior treatment with any PI3K, AKT, or mTOR inhibitor, or any agent whose mechanism of action is to inhibit the PI3K-AKT-mTOR pathway
* Type 2 diabetes requiring ongoing systemic treatment at the time of study entry; or any history of Type 1 diabetes
* Known and untreated, or active CNS metastases. Patients with a history of treated CNS metastases may be eligible
* Active inflammatory or infectious conditions in either eye, or any eye conditions expected to require surgery during the study treatment period
* Symptomatic active lung disease, or requiring daily supplemental oxygen
* History of inflammatory bowel disease or active bowel inflammation
* Anti-cancer therapy within 2 weeks before study entry
* Investigational drug(s) within 4 weeks before randomization
* Prior radiotherapy to >= 25% of bone marrow, or hematopoietic stem cell or bone marrow transplantation
* Chronic corticosteroid therapy or immunosuppressants
* Pregnant, lactating, or breastfeeding, or intending to become pregnant during the study or within 60 days after the final dose of study treatment
* Major surgical procedure, or significant traumatic injury, within 28 days prior to Day 1 of Cycle 1

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 analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
29/01/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/09/2030
Actual
Sample size
Target
Accrual to date
Final
325
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Macquarie University Hospital - Macquarie Park
Recruitment hospital [2] 0 0
Westmead Hospital; Medical Oncology and Pallative Care - Westmead
Recruitment hospital [3] 0 0
Southern Medical Day Care Centre - Wollongong
Recruitment hospital [4] 0 0
Mater Adult Hospital; Oncology - South Brisbane
Recruitment hospital [5] 0 0
Princess Alexandra Hospital; Cancer Trials Unit - Woolloongabba
Recruitment hospital [6] 0 0
Western Health - Fitzroy
Recruitment hospital [7] 0 0
Peninsula and South Eastern Haematology and Oncology Group - Frankston
Recruitment postcode(s) [1] 0 0
2113 - Macquarie Park
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
2500 - Wollongong
Recruitment postcode(s) [4] 0 0
4101 - South Brisbane
Recruitment postcode(s) [5] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [6] 0 0
3065 - Fitzroy
Recruitment postcode(s) [7] 0 0
3199 - Frankston
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
Georgia
Country [3] 0 0
United States of America
State/province [3] 0 0
Massachusetts
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
North Carolina
Country [6] 0 0
United States of America
State/province [6] 0 0
Tennessee
Country [7] 0 0
United States of America
State/province [7] 0 0
Texas
Country [8] 0 0
United States of America
State/province [8] 0 0
Washington
Country [9] 0 0
Argentina
State/province [9] 0 0
Buenos Aires
Country [10] 0 0
Argentina
State/province [10] 0 0
Ciudad Autonoma Buenos Aires
Country [11] 0 0
Argentina
State/province [11] 0 0
Rosario
Country [12] 0 0
Argentina
State/province [12] 0 0
Viedma
Country [13] 0 0
Belgium
State/province [13] 0 0
Leuven
Country [14] 0 0
Brazil
State/province [14] 0 0
GO
Country [15] 0 0
Brazil
State/province [15] 0 0
RS
Country [16] 0 0
Brazil
State/province [16] 0 0
SP
Country [17] 0 0
Canada
State/province [17] 0 0
Alberta
Country [18] 0 0
Canada
State/province [18] 0 0
Ontario
Country [19] 0 0
Canada
State/province [19] 0 0
Quebec
Country [20] 0 0
China
State/province [20] 0 0
Beijing
Country [21] 0 0
China
State/province [21] 0 0
Changchun City
Country [22] 0 0
China
State/province [22] 0 0
Chengdu
Country [23] 0 0
China
State/province [23] 0 0
Chongqing
Country [24] 0 0
China
State/province [24] 0 0
Fuzhou City
Country [25] 0 0
China
State/province [25] 0 0
Guangzhou City
Country [26] 0 0
China
State/province [26] 0 0
Hangzhou City
Country [27] 0 0
China
State/province [27] 0 0
Harbin
Country [28] 0 0
China
State/province [28] 0 0
Nanjing City
Country [29] 0 0
China
State/province [29] 0 0
Shanghai City
Country [30] 0 0
China
State/province [30] 0 0
Shijiazhuang
Country [31] 0 0
China
State/province [31] 0 0
Tianjin
Country [32] 0 0
China
State/province [32] 0 0
Wuhan City
Country [33] 0 0
China
State/province [33] 0 0
Wuhan
Country [34] 0 0
China
State/province [34] 0 0
Xi'an
Country [35] 0 0
China
State/province [35] 0 0
Zhengzhou
Country [36] 0 0
Denmark
State/province [36] 0 0
Vejle
Country [37] 0 0
France
State/province [37] 0 0
Clermont-ferrand
Country [38] 0 0
France
State/province [38] 0 0
Dijon
Country [39] 0 0
France
State/province [39] 0 0
Lille
Country [40] 0 0
France
State/province [40] 0 0
Limoges
Country [41] 0 0
France
State/province [41] 0 0
Lyon
Country [42] 0 0
France
State/province [42] 0 0
Montpellier
Country [43] 0 0
France
State/province [43] 0 0
Toulouse
Country [44] 0 0
Georgia
State/province [44] 0 0
Tbilisi
Country [45] 0 0
Germany
State/province [45] 0 0
Berlin
Country [46] 0 0
Germany
State/province [46] 0 0
Essen
Country [47] 0 0
Germany
State/province [47] 0 0
Heidelberg
Country [48] 0 0
Germany
State/province [48] 0 0
Mannheim
Country [49] 0 0
Germany
State/province [49] 0 0
Trier
Country [50] 0 0
Germany
State/province [50] 0 0
Ulm
Country [51] 0 0
Greece
State/province [51] 0 0
Athens
Country [52] 0 0
Greece
State/province [52] 0 0
Heraklion
Country [53] 0 0
Greece
State/province [53] 0 0
Thessaloniki
Country [54] 0 0
Hong Kong
State/province [54] 0 0
Hong Kong
Country [55] 0 0
Hong Kong
State/province [55] 0 0
Shatin
Country [56] 0 0
Hungary
State/province [56] 0 0
Budapest
Country [57] 0 0
Hungary
State/province [57] 0 0
Debrecen
Country [58] 0 0
Hungary
State/province [58] 0 0
Szolnok
Country [59] 0 0
Italy
State/province [59] 0 0
Campania
Country [60] 0 0
Italy
State/province [60] 0 0
Emilia-Romagna
Country [61] 0 0
Italy
State/province [61] 0 0
Friuli-Venezia Giulia
Country [62] 0 0
Italy
State/province [62] 0 0
Lombardia
Country [63] 0 0
Italy
State/province [63] 0 0
Toscana
Country [64] 0 0
Italy
State/province [64] 0 0
Veneto
Country [65] 0 0
Korea, Republic of
State/province [65] 0 0
Busan
Country [66] 0 0
Korea, Republic of
State/province [66] 0 0
Daegu
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
Seongnam-si
Country [69] 0 0
Korea, Republic of
State/province [69] 0 0
Seoul
Country [70] 0 0
Malaysia
State/province [70] 0 0
Federal Territory OF Putrajaya
Country [71] 0 0
Malaysia
State/province [71] 0 0
Johor
Country [72] 0 0
Malaysia
State/province [72] 0 0
Sarawak
Country [73] 0 0
New Zealand
State/province [73] 0 0
Palmerston North
Country [74] 0 0
Poland
State/province [74] 0 0
Gliwice
Country [75] 0 0
Poland
State/province [75] 0 0
Konin
Country [76] 0 0
Poland
State/province [76] 0 0
Opole
Country [77] 0 0
Poland
State/province [77] 0 0
Torun
Country [78] 0 0
Poland
State/province [78] 0 0
Warszawa
Country [79] 0 0
Portugal
State/province [79] 0 0
Lisboa
Country [80] 0 0
Portugal
State/province [80] 0 0
Porto
Country [81] 0 0
Russian Federation
State/province [81] 0 0
Moskovskaja Oblast
Country [82] 0 0
Russian Federation
State/province [82] 0 0
Sankt Petersburg
Country [83] 0 0
Russian Federation
State/province [83] 0 0
Volgograd
Country [84] 0 0
Russian Federation
State/province [84] 0 0
Yaroslavl
Country [85] 0 0
Singapore
State/province [85] 0 0
Singapore
Country [86] 0 0
Spain
State/province [86] 0 0
Alicante
Country [87] 0 0
Spain
State/province [87] 0 0
Barcelona
Country [88] 0 0
Spain
State/province [88] 0 0
Madrid
Country [89] 0 0
Spain
State/province [89] 0 0
Navarra
Country [90] 0 0
Spain
State/province [90] 0 0
Tenerife
Country [91] 0 0
Spain
State/province [91] 0 0
Jaen
Country [92] 0 0
Spain
State/province [92] 0 0
Sevilla
Country [93] 0 0
Spain
State/province [93] 0 0
Valencia
Country [94] 0 0
Taiwan
State/province [94] 0 0
Kaohsiung
Country [95] 0 0
Taiwan
State/province [95] 0 0
Tainan
Country [96] 0 0
Taiwan
State/province [96] 0 0
Taipei City
Country [97] 0 0
Taiwan
State/province [97] 0 0
Taipei
Country [98] 0 0
Thailand
State/province [98] 0 0
Bangkok
Country [99] 0 0
Thailand
State/province [99] 0 0
Chiang Mai
Country [100] 0 0
Thailand
State/province [100] 0 0
Lak Si
Country [101] 0 0
Thailand
State/province [101] 0 0
Songkhla
Country [102] 0 0
Turkey
State/province [102] 0 0
Adana
Country [103] 0 0
Turkey
State/province [103] 0 0
Ankara
Country [104] 0 0
Turkey
State/province [104] 0 0
Bornova, ?zm?r
Country [105] 0 0
Turkey
State/province [105] 0 0
Istanbul
Country [106] 0 0
Ukraine
State/province [106] 0 0
Kharkiv Governorate
Country [107] 0 0
Ukraine
State/province [107] 0 0
KIEV Governorate
Country [108] 0 0
Ukraine
State/province [108] 0 0
Dnipropetrovsk
Country [109] 0 0
Ukraine
State/province [109] 0 0
Kryvyi Rih
Country [110] 0 0
Ukraine
State/province [110] 0 0
Kyiv
Country [111] 0 0
Ukraine
State/province [111] 0 0
Sumy
Country [112] 0 0
United Kingdom
State/province [112] 0 0
Bristol
Country [113] 0 0
United Kingdom
State/province [113] 0 0
Harlow
Country [114] 0 0
United Kingdom
State/province [114] 0 0
London
Country [115] 0 0
United Kingdom
State/province [115] 0 0
Manchester
Country [116] 0 0
United Kingdom
State/province [116] 0 0
Northwood
Country [117] 0 0
United Kingdom
State/province [117] 0 0
Oxford
Country [118] 0 0
United Kingdom
State/province [118] 0 0
Peterborough
Country [119] 0 0
United Kingdom
State/province [119] 0 0
Plymouth
Country [120] 0 0
United Kingdom
State/province [120] 0 0
Portsmouth
Country [121] 0 0
United Kingdom
State/province [121] 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
This study will evaluate the efficacy, safety, and pharmacokinetics of inavolisib in combination with palbociclib and fulvestrant compared with placebo plus palbociclib and fulvestrant in participants with PIK3CA-mutant, hormone receptor (HR)-positive, HER2-negative locally advanced or metastatic breast cancer whose disease progressed during treatment or within 12 months of completing adjuvant endocrine therapy and who have not received prior systemic therapy for metastatic disease.
Trial website
https://clinicaltrials.gov/study/NCT04191499
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