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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04987203




Registration number
NCT04987203
Ethics application status
Date submitted
23/07/2021
Date registered
3/08/2021
Date last updated
30/04/2024

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
1/08/2025
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
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United States of America
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California
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Colorado
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Michigan
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Napoli
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Roma
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Barcelona
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Madrid
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Manchester
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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/ct2/show/NCT04987203
Trial related presentations / publications
Public notes

Contacts
Principal investigator
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Contact person for public queries
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Contact person for scientific queries