Trial Review

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/NCT04987203




Registration number
NCT04987203
Ethics application status
Date submitted
23/07/2021
Date registered
3/08/2021
Date last updated
24/10/2024

Titles & IDs
Public title
Study to Compare Tivozanib in Combination With Nivolumab to Tivozanib Monotherapy in Subjects With Renal Cell Carcinoma
Scientific title
TiNivo-2: A Phase 3, Randomized, Controlled, Multicenter, Open-label Study to Compare Tivozanib in Combination With Nivolumab to Tivozanib Monotherapy in Subjects With Renal Cell Carcinoma Who Have Progressed Following One or Two Lines of Therapy Where One Line Has an Immune Checkpoint Inhibitor
Secondary ID [1] 0 0
AV-951-20-304
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Renal Cell Carcinoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Tivozanib
Treatment: Drugs - Nivolumab

Experimental: Tivozanib in Combination with Nivolumab - Subjects with advanced RCC will receive 0.89 mg of tivozanib once daily (QD) for 3 weeks followed by 1 week off study drug and nivolumab every 4 weeks on Day 1 of each Cycle, until disease progression or unacceptable toxicities occur, other withdrawal criteria are met, or completion of 2 years of treatment \[for nivolumab\] whichever occurs first.

Experimental: Tivozanib - Subjects with advanced RCC will receive 1.34 mg of tivozanib once daily (QD) for 3 weeks followed by 1 week off study drug until disease progression or unacceptable toxicities occur, or other withdrawal criteria are met.


Treatment: Drugs: Tivozanib
Tivozanib will be administered orally.

Treatment: Drugs: Nivolumab
Nivolumab will be administered via intravenous infusion.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression free survival
Timepoint [1] 0 0
Until progressive disease [PD] (Approximately 30 months)
Secondary outcome [1] 0 0
Overall Survival
Timepoint [1] 0 0
From Screening (Days -28 to -1) until death (Approximately 42 months)
Secondary outcome [2] 0 0
Progression free survival
Timepoint [2] 0 0
Until progressive disease [PD] (Approximately 30 months)
Secondary outcome [3] 0 0
Objective Response Rate
Timepoint [3] 0 0
From Screening (Days -28 to -1) until PD (Approximately 30 months)
Secondary outcome [4] 0 0
Duration of Response
Timepoint [4] 0 0
From Screening (Days -28 to -1) until PD or death (Approximately 30 months)
Secondary outcome [5] 0 0
Number of subjects with serious and non-serious adverse events
Timepoint [5] 0 0
From Screening (Day -28 to Day -1) to Follow-up visit (30 days after last dose of study drug ± 7 days)

Eligibility
Key inclusion criteria
* Radiographic disease progression during or following at least 6 weeks of treatment with ICI for locally advanced or metastatic RCC with a clear cell component either in first- or second-line treatment.
* Subjects must have recovered from the adverse events of prior therapy to grade = 1 or baseline.
* Histologically or cytologically confirmed RCC with a clear cell component.
* Measurable disease per RECIST criteria Version 1.1.
* Eastern Cooperative Oncology Group performance status of 0 or 1.
* All participants must follow protocol defined contraceptive measures.
Minimum age
18 Years
Maximum age
130 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Subjects who received: a. A single agent tyrosine kinase inhibitor (TKI) in the first line setting followed by a single agent immune checkpoint inhibitor (ICI) in the second line setting; b. More than 2 prior lines of therapy in the advanced or metastatic setting.
* History of life-threatening toxicity related to prior immune therapy.
* Active autoimmune disease as well as those that required discontinuation of prior immuno-oncological (IO) therapy due to immune mediated AEs.
* Uncontrolled hypertension.
* More than 1 prior line of therapy with a checkpoint inhibitor in the metastatic setting.
* Subjects on immune suppressive therapy for organ transplant or subjects with a history of genetic or acquired immune suppression disease such as human immunodeficiency virus (HIV) [Patients with HIV who have CD4+ T-cell counts >350 cells/µL, without a history of acquired immune deficiency syndrome (AIDS)-defining opportunistic infections, and are on established antiretroviral therapy which does not include a cytochrome P450 (CYP)3A4 inducer, for at least 4 weeks and have an HIV viral load less than 400 copies/mL, are eligible].
* History of clinically significant interstitial lung disease or current non-infectious pneumonitis.

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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
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
9/09/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/07/2026
Actual
Sample size
Target
Accrual to date
Final
343
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Liverpool Hospital Cancer Therapy Centre - Liverpool
Recruitment hospital [2] 0 0
Mater Misericordiae Limited - Brisbane
Recruitment hospital [3] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [4] 0 0
Sunshine Hospital - Geelong
Recruitment postcode(s) [1] 0 0
2170 - Liverpool
Recruitment postcode(s) [2] 0 0
4101 - Brisbane
Recruitment postcode(s) [3] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [4] 0 0
3220 - Geelong
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
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Kansas
Country [5] 0 0
United States of America
State/province [5] 0 0
Kentucky
Country [6] 0 0
United States of America
State/province [6] 0 0
Louisiana
Country [7] 0 0
United States of America
State/province [7] 0 0
Maryland
Country [8] 0 0
United States of America
State/province [8] 0 0
Massachusetts
Country [9] 0 0
United States of America
State/province [9] 0 0
Michigan
Country [10] 0 0
United States of America
State/province [10] 0 0
Montana
Country [11] 0 0
United States of America
State/province [11] 0 0
Nebraska
Country [12] 0 0
United States of America
State/province [12] 0 0
New Jersey
Country [13] 0 0
United States of America
State/province [13] 0 0
New Mexico
Country [14] 0 0
United States of America
State/province [14] 0 0
New York
Country [15] 0 0
United States of America
State/province [15] 0 0
Ohio
Country [16] 0 0
United States of America
State/province [16] 0 0
Pennsylvania
Country [17] 0 0
United States of America
State/province [17] 0 0
South Carolina
Country [18] 0 0
United States of America
State/province [18] 0 0
Tennessee
Country [19] 0 0
United States of America
State/province [19] 0 0
Texas
Country [20] 0 0
United States of America
State/province [20] 0 0
Washington
Country [21] 0 0
Argentina
State/province [21] 0 0
Ciudad Autónoma De Buenos Aire
Country [22] 0 0
Argentina
State/province [22] 0 0
Río Negro
Country [23] 0 0
Argentina
State/province [23] 0 0
Santa Fe
Country [24] 0 0
Argentina
State/province [24] 0 0
Tucumán
Country [25] 0 0
Belgium
State/province [25] 0 0
Antwerpen
Country [26] 0 0
Belgium
State/province [26] 0 0
Brussels Capital Region
Country [27] 0 0
Belgium
State/province [27] 0 0
Limburg
Country [28] 0 0
Belgium
State/province [28] 0 0
Oost-Vlaanderen
Country [29] 0 0
Belgium
State/province [29] 0 0
Bruxelles
Country [30] 0 0
Belgium
State/province [30] 0 0
Kortrijk
Country [31] 0 0
Brazil
State/province [31] 0 0
Rio Grande Do Sul
Country [32] 0 0
Brazil
State/province [32] 0 0
Santa Catarina
Country [33] 0 0
Brazil
State/province [33] 0 0
São Paulo
Country [34] 0 0
Brazil
State/province [34] 0 0
Porto Alegre
Country [35] 0 0
Canada
State/province [35] 0 0
Alberta
Country [36] 0 0
Canada
State/province [36] 0 0
British Columbia
Country [37] 0 0
Canada
State/province [37] 0 0
Ontario
Country [38] 0 0
Chile
State/province [38] 0 0
Región Metropolitana De Santiago
Country [39] 0 0
Chile
State/province [39] 0 0
Región Metropolitana De Santia
Country [40] 0 0
Chile
State/province [40] 0 0
Valparaíso
Country [41] 0 0
Czechia
State/province [41] 0 0
Hradec Kralove
Country [42] 0 0
Czechia
State/province [42] 0 0
Praha 10
Country [43] 0 0
Czechia
State/province [43] 0 0
Praha 4
Country [44] 0 0
France
State/province [44] 0 0
Alsace
Country [45] 0 0
France
State/province [45] 0 0
Bouches-du-Rhône
Country [46] 0 0
France
State/province [46] 0 0
Gironde
Country [47] 0 0
France
State/province [47] 0 0
Hauts-de-Seine
Country [48] 0 0
France
State/province [48] 0 0
Isère
Country [49] 0 0
France
State/province [49] 0 0
Nord
Country [50] 0 0
France
State/province [50] 0 0
Poitou-Charentes
Country [51] 0 0
France
State/province [51] 0 0
Rhône-Alpes
Country [52] 0 0
France
State/province [52] 0 0
Rhône
Country [53] 0 0
France
State/province [53] 0 0
Sarthe
Country [54] 0 0
France
State/province [54] 0 0
La Roche-sur-Yon
Country [55] 0 0
France
State/province [55] 0 0
Nice
Country [56] 0 0
France
State/province [56] 0 0
St Herblain
Country [57] 0 0
France
State/province [57] 0 0
Tours
Country [58] 0 0
France
State/province [58] 0 0
Vandœuvre-lès-Nancy
Country [59] 0 0
France
State/province [59] 0 0
Île-de-France
Country [60] 0 0
Germany
State/province [60] 0 0
Baden-Württemberg
Country [61] 0 0
Germany
State/province [61] 0 0
Niedersachsen
Country [62] 0 0
Italy
State/province [62] 0 0
Chieti
Country [63] 0 0
Italy
State/province [63] 0 0
Forli
Country [64] 0 0
Italy
State/province [64] 0 0
Arezzo
Country [65] 0 0
Italy
State/province [65] 0 0
Catanzaro
Country [66] 0 0
Italy
State/province [66] 0 0
Cremona
Country [67] 0 0
Italy
State/province [67] 0 0
Firenze
Country [68] 0 0
Italy
State/province [68] 0 0
Milano
Country [69] 0 0
Italy
State/province [69] 0 0
Napoli
Country [70] 0 0
Italy
State/province [70] 0 0
Pavia
Country [71] 0 0
Italy
State/province [71] 0 0
Roma
Country [72] 0 0
Italy
State/province [72] 0 0
Terni
Country [73] 0 0
Mexico
State/province [73] 0 0
Tlalpan
Country [74] 0 0
Poland
State/province [74] 0 0
Malopolskie
Country [75] 0 0
Poland
State/province [75] 0 0
Mazowieckie
Country [76] 0 0
Poland
State/province [76] 0 0
Podkarpackie
Country [77] 0 0
Poland
State/province [77] 0 0
Pomorskie
Country [78] 0 0
Poland
State/province [78] 0 0
Wielkopolskie
Country [79] 0 0
Poland
State/province [79] 0 0
Biala Podlaska
Country [80] 0 0
Poland
State/province [80] 0 0
Warszawa
Country [81] 0 0
Portugal
State/province [81] 0 0
Lisboa
Country [82] 0 0
Portugal
State/province [82] 0 0
Faro
Country [83] 0 0
Portugal
State/province [83] 0 0
Porto
Country [84] 0 0
Spain
State/province [84] 0 0
Alicante
Country [85] 0 0
Spain
State/province [85] 0 0
Baleares
Country [86] 0 0
Spain
State/province [86] 0 0
Barcelona
Country [87] 0 0
Spain
State/province [87] 0 0
Valenciana, Comunidad
Country [88] 0 0
Spain
State/province [88] 0 0
Girona
Country [89] 0 0
Spain
State/province [89] 0 0
Madrid
Country [90] 0 0
Spain
State/province [90] 0 0
Orense
Country [91] 0 0
Spain
State/province [91] 0 0
Sevilla
Country [92] 0 0
Spain
State/province [92] 0 0
Valencia
Country [93] 0 0
United Kingdom
State/province [93] 0 0
Cambridgeshire
Country [94] 0 0
United Kingdom
State/province [94] 0 0
England
Country [95] 0 0
United Kingdom
State/province [95] 0 0
Lancashire
Country [96] 0 0
United Kingdom
State/province [96] 0 0
London, City Of
Country [97] 0 0
United Kingdom
State/province [97] 0 0
Surrey
Country [98] 0 0
United Kingdom
State/province [98] 0 0
Derby
Country [99] 0 0
United Kingdom
State/province [99] 0 0
Leeds
Country [100] 0 0
United Kingdom
State/province [100] 0 0
Manchester
Country [101] 0 0
United Kingdom
State/province [101] 0 0
Wolverhampton

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AVEO Pharmaceuticals, Inc.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Parexel
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/industry
Name [2] 0 0
Bristol-Myers Squibb
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This study will be comparing tivozanib in combination with nivolumab to tivozanib alone in subjects with advanced Renal Cell Carcinoma (RCC) who have had 1 or 2 prior lines of therapy, one of which was an Immune Checkpoint Inhibitor (ICI).
Trial website
https://clinicaltrials.gov/study/NCT04987203
Trial related presentations / publications
Yang Y, Psutka SP, Parikh AB, Li M, Collier K, Miah A, Mori SV, Hinkley M, Tykodi SS, Hall E, Thompson JA, Yin M. Combining immune checkpoint inhibition plus tyrosine kinase inhibition as first and subsequent treatments for metastatic renal cell carcinoma. Cancer Med. 2022 Aug;11(16):3106-3114. doi: 10.1002/cam4.4679. Epub 2022 Mar 18.
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
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



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT04987203