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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03682068




Registration number
NCT03682068
Ethics application status
Date submitted
6/09/2018
Date registered
24/09/2018
Date last updated
25/09/2024

Titles & IDs
Public title
Study of Durvalumab Given With Chemotherapy, Durvalumab in Combination With Tremelimumab Given With Chemotherapy, or Chemotherapy in Patients With Unresectable Urothelial Cancer
Scientific title
A Phase III, Randomized, Open-Label, Controlled, Multi-Center, Global Study of First-Line Durvalumab in Combination With Standard of Care Chemotherapy and Durvalumab in Combination With Tremelimumab and Standard of Care Chemotherapy Versus Standard of Care Chemotherapy Alone in Patients With Unresectable Locally Advanced or Metastatic Urothelial Cancer.
Secondary ID [1] 0 0
2018-001883-48
Secondary ID [2] 0 0
D933SC00001
Universal Trial Number (UTN)
Trial acronym
NILE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Unresectable Locally Advanced Urothelial Cancer 0 0
Metastatic Urothelial Cancer 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Durvalumab
Treatment: Drugs - Tremelimumab
Treatment: Drugs - Cisplatin + Gemcitabine
Treatment: Drugs - Carboplatin + Gemcitabine

Experimental: Durvalumab in Combination with SoC Chemotherapy - Durvalumab every 3 weeks in concurrence with chemotherapy, followed by durvalumab monotherapy every 4 weeks.

All patients will receive one of the following standard of care chemotherapy regimens every 3 weeks for 6 cycles:

* cisplatin+ gemcitabine
* If the patient is cisplatin-ineligible, carboplatin + gemcitabine

Experimental: Durvalumab in Combination with Tremelimumab+SoC Chemotherapy - Durvalumab and Tremelimumab every 3 weeks in concurrence with chemotherapy, followed by durvalumab monotherapy every 4 weeks

Tremelimumab will be provided for 4 cycles.

All patients will receive one of the following standard of care chemotherapy regimens every 3 weeks for 6 cycles:

* cisplatin+ gemcitabine
* If the patient is cisplatin-ineligible, carboplatin + gemcitabine

Active comparator: SoC Chemotherapy - Patients will receive one of the following standard of care chemotherapy regimens every 3 weeks for 6 cycles:

* cisplatin+ gemcitabine
* If the patient is cisplatin-ineligible, carboplatin + gemcitabine


Treatment: Drugs: Durvalumab
Durvalumab IV (intravenous infusion)

Treatment: Drugs: Tremelimumab
Tremelimumab IV (intravenous infusion)

Treatment: Drugs: Cisplatin + Gemcitabine
Cisplatin IV (intravenous)+ Gemcitabine IV(intravenous), as standard of care.

Treatment: Drugs: Carboplatin + Gemcitabine
Carboplatin IV (intravenous)+ Gemcitabine IV(intravenous), as standard of care.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
approximately 5 years
Secondary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
approximately 5 years
Secondary outcome [2] 0 0
Overall Survival at 24 months (OS24)
Timepoint [2] 0 0
24 months
Secondary outcome [3] 0 0
Progression Free Survival (PFS)
Timepoint [3] 0 0
approximately 5 years
Secondary outcome [4] 0 0
Alive and Progression Free Survival at 12 months (APF12)
Timepoint [4] 0 0
12 months
Secondary outcome [5] 0 0
Objective Response Rate (ORR)
Timepoint [5] 0 0
approximately 5 years
Secondary outcome [6] 0 0
Duration of Response (DoR)
Timepoint [6] 0 0
approximately 5 years
Secondary outcome [7] 0 0
Disease Control Rate (DCR)
Timepoint [7] 0 0
approximately 5 years
Secondary outcome [8] 0 0
Time from randomization to second (PFS2)
Timepoint [8] 0 0
approximately 5 years
Secondary outcome [9] 0 0
To assess disease-related symptoms, physical functioning, and other Health-related quality of life
Timepoint [9] 0 0
approximately 5 years

Eligibility
Key inclusion criteria
Key

* Patients with histologically or cytologically documented, unresectable, locally advanced or metastatic transitional cell carcinoma (transitional cell and mixed transitional/non-transitional cell histologies) of the urothelium (including renal pelvis, ureters, urinary bladder, and urethra)
* Patients who have not been previously treated with first-line chemotherapy. Patients who have received prior definitive chemoradiation, adjuvant or neoadjuvant treatment for locally advanced disease are eligible provided that progression to locally advanced or metastatic disease has occurred >12 months from the last therapy [for chemoradiation and adjuvant treatment] or >12 months from the last surgery [for neoadjuvant treatment].
* At least 1 lesion, not previously irradiated, that qualifies as a RECIST 1.1 target lesion at baseline.
* World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 at enrolment
* Adequate organ and marrow function as defined in the protocol
* Life expectancy =12 weeks in the opinion of the investigator
* Evidence of post-menopausal status, or negative urinary or serum pregnancy test for female pre-menopausal patients.

Key
Minimum age
18 Years
Maximum age
130 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Prior exposure to immune-mediated therapy (with exclusion of Bacillus Calmette Guerin), including but not limited to, other anti-CTLA-4, anti-PD-1, anti-PD L1, or anti-PD-L2 antibodies, except therapeutic anticancer vaccines, which are permitted. Prior local intervesical chemotherapy or immunotherapy is allowed if completed at least 28 days prior to the initiation of study treatment.
* No severe concomitant condition that requires immunosuppression medication
* Untreated central nervous system (CNS) metastases and/or carcinomatous meningitis
* Patients who may be eligible for or are being considered for radical resection during the course of the study.
* Any medical contraindications to platinum (cisplatin or carboplatin) based doublet chemotherapy and/or known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients

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
27/09/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/06/2025
Actual
Sample size
Target
Accrual to date
Final
1246
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Box Hill
Recruitment hospital [2] 0 0
Research Site - Elizabeth Vale
Recruitment hospital [3] 0 0
Research Site - Kogarah
Recruitment hospital [4] 0 0
Research Site - Macquarie University
Recruitment hospital [5] 0 0
Research Site - Murdoch
Recruitment hospital [6] 0 0
Research Site - Orange
Recruitment hospital [7] 0 0
Research Site - South Brisbane
Recruitment hospital [8] 0 0
Research Site - St Albans
Recruitment postcode(s) [1] 0 0
3128 - Box Hill
Recruitment postcode(s) [2] 0 0
5112 - Elizabeth Vale
Recruitment postcode(s) [3] 0 0
2217 - Kogarah
Recruitment postcode(s) [4] 0 0
2109 - Macquarie University
Recruitment postcode(s) [5] 0 0
6150 - Murdoch
Recruitment postcode(s) [6] 0 0
2800 - Orange
Recruitment postcode(s) [7] 0 0
4101 - South Brisbane
Recruitment postcode(s) [8] 0 0
3021 - St Albans
Recruitment outside Australia
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United States of America
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Alabama
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California
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Tennessee
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Texas
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Argentina
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Rosario
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Fortaleza
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Miyazaki-city
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Osakasayama-shi
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Yokohama-shi
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Kraków
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Ivanovo
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Krasnoyarsk
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Russian Federation
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Moscow
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Omsk
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Rostov-on-Don
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Tyumen
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Vologda
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Barcelona
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Lugo
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Malaga
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Sevilla
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Taoyuan
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Bangkok
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Khon Kaen
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Mueang
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Songkla
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Turkey
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Adana
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Ankara
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Edirne
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Ha Noi
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Hanoi
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Vietnam
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Ho Chi Minh

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AstraZeneca
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a randomized, open-label, controlled, multi-center, global Phase III study to determine the efficacy and safety of combining durvalumab ± tremelimumab with standard of care (SoC) chemotherapy (cisplatin + gemcitabine or carboplatin + gemcitabine doublet) followed by durvalumab monotherapy versus SoC alone as first-line chemotherapy in patients with histologically or cytologically documented, unresectable, locally advanced or metastatic transitional cell carcinoma of the urothelium (including renal pelvis, ureters, urinary bladder, and urethra).
Trial website
https://clinicaltrials.gov/study/NCT03682068
Trial related presentations / publications
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/NCT03682068