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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02516241




Registration number
NCT02516241
Ethics application status
Date submitted
13/07/2015
Date registered
5/08/2015
Date last updated
10/07/2020

Titles & IDs
Public title
Study of MEDI4736 (Durvalumab) With or Without Tremelimumab Versus Standard of Care Chemotherapy in Urothelial Cancer
Scientific title
A Phase III, Randomized, Open-Label, Controlled, Multi-Center, Global Study of First-Line MEDI4736 (Durvalumab) Monotherapy and MEDI4736 (Durvalumab) in Combination With Tremelimumab Versus Standard of Care Chemotherapy in Patients With Unresectable Stage IV Urothelial Cancer
Secondary ID [1] 0 0
D419BC00001
Universal Trial Number (UTN)
Trial acronym
Linked study record

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

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - MEDI4736 (Durvalumab)
Treatment: Drugs - Tremelimumab
Treatment: Drugs - Cisplatin
Treatment: Drugs - Carboplatin
Treatment: Drugs - Gemcitabine

Experimental: Combination Therapy - MEDI4736 (Durvalumab) + Tremelimumab

Experimental: Monotherapy - MEDI4736 (Durvalumab)

Active Comparator: Standard of Care - Standard of Care Chemotherapy Treatment


Treatment: Drugs: MEDI4736 (Durvalumab)
IV infusion

Treatment: Drugs: Tremelimumab
IV infusion

Treatment: Drugs: Cisplatin
IV infusion

Treatment: Drugs: Carboplatin
IV infusion

Treatment: Drugs: Gemcitabine
IV infusion

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
To assess the efficacy of MEDI4736 + tremelimumab combination therapy versus SoC in terms of OS in patients with unresectable Stage IV UC
Timepoint [1] 0 0
Up to 7 years
Primary outcome [2] 0 0
To assess the efficacy of MEDI4736 monotherapy versus SoC in terms of OS in patients with unresectable Stage IV PD-L1- High UC
Timepoint [2] 0 0
up to 7 years
Secondary outcome [1] 0 0
To assess the efficacy of MEDI4736 monotherapy compared to SoC in terms of PFS in patients with PD-L1-High UC
Timepoint [1] 0 0
5 years
Secondary outcome [2] 0 0
To assess the efficacy of MEDI4736 + tremelimumab combination therapy versus SoC in terms of PFS in patients with UC
Timepoint [2] 0 0
5 years
Secondary outcome [3] 0 0
To further assess the efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of ORR
Timepoint [3] 0 0
5 years
Secondary outcome [4] 0 0
To further assess the efficacy of MEDI4736 monotherapy compared to SoC in terms of ORR
Timepoint [4] 0 0
5 years
Secondary outcome [5] 0 0
To assess disease-related symptoms and HRQoL in UC patients treated with MEDI4736 monotherapy and MEDI4736 + tremelimumab combination therapy compared with SoC and each other using the FACT-BL questionnaire
Timepoint [5] 0 0
5 years
Secondary outcome [6] 0 0
To assess the serum concentration of MEDI4736/tremelimumab of MEDI4736 monotherapy and MEDI4736 + tremelimumab combination therapy
Timepoint [6] 0 0
up to 6 months
Secondary outcome [7] 0 0
To investigate the immunogenicity of MEDI4736 monotherapy and MEDI4736 + tremelimumab combination therapy
Timepoint [7] 0 0
5 years
Secondary outcome [8] 0 0
To assess the objective response rate (ORR) of MEDI4736 monotherapy in patients who are not cisplatin-eligible
Timepoint [8] 0 0
5 years
Secondary outcome [9] 0 0
To assess the duration of response (DoR) of MEDI4736 monotherapy in patients who are not cisplatin-eligible
Timepoint [9] 0 0
5 years

Eligibility
Key inclusion criteria
- Patients with histologically or cytologically documented, unresectable, Stage IV
transitional cell carcinoma of the urothelium who have not been previously treated
with first-line chemotherapy.

- Patients eligible or ineligible for cisplatin-based chemotherapy. Cisplatin
ineligibility is defined as meeting 1 of the following criteria: • Creatinine
clearance (calculated or measured) <60 mL/min calculated by Cockcroft-Gault equation
(using actual body weight) or by measured 24-hour urine collection for determination •
Common Terminology Criteria for Adverse Events (CTCAE) Grade =2 audiometric hearing
loss • CTCAE Grade =2 peripheral neuropathy • New York Heart Association =Class III
heart failure.

- Tumor PD-L1 status, with Immunohistochemical (IHC) assay confirmed by a reference
laboratory, must be known prior to randomization.
Minimum age
18 Years
Maximum age
130 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Prior exposure to immune-mediated therapy, including but not limited to, other anti
cytotoxic T-lymphocyte-associated protein 4 (CTLA 4), anti-PD-1, anti-PD-L1, or
anti-PD-L2 antibodies, including therapeutic anticancer vaccines. Prior local
intervesical chemotherapy or immunotherapy is allowed if completed at least 28 days
prior to the initiation of study treatment.

- History of allogenic organ transplantation that requires use of immunosuppressive
agents.

- Active or prior documented autoimmune or inflammatory disorders. The following are
exceptions to this criterion: • Patients with vitiligo or alopecia • Patients with
hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement • Any
chronic skin condition that does not require systemic therapy • Patients without
active disease in the last 3 years may be included but only after consultation with
AstraZeneca • Patients with celiac disease controlled by diet alone may be included
but only after consultation with AstraZeneca.

- Brain metastases or spinal cord compression unless the patient's condition is stable
and off steroids for at least 14 days prior to the start of study treatment. Patients
with suspected or known brain metastases at screening should have an MRI
(preferred)/CT, preferably with IV contrast to access baseline disease status.

- Active infection including tuberculosis, hepatitis B, hepatitis C, or human
immunodeficiency virus (HIV).

- Current or prior use of immunosuppressive medication within 14 days before the first
dose of investigational product (IP). The following are exceptions to this criterion:
• Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra
articular injection) • Systemic corticosteroids at physiologic doses not to exceed 10
mg/day of prednisone or its equivalent • Steroids as premedication for
hypersensitivity reactions (eg, CT scan premedication).

- Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note:
Patients, if enrolled, should not receive live vaccine during the study and up to 30
days after the last dose of IP.

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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
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 - Macquarie University
Recruitment hospital [4] 0 0
Research Site - St Leonards
Recruitment hospital [5] 0 0
Research Site - Waratah
Recruitment postcode(s) [1] 0 0
3128 - Box Hill
Recruitment postcode(s) [2] 0 0
5112 - Elizabeth Vale
Recruitment postcode(s) [3] 0 0
2109 - Macquarie University
Recruitment postcode(s) [4] 0 0
2065 - St Leonards
Recruitment postcode(s) [5] 0 0
2298 - Waratah
Recruitment outside Australia
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United States of America
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California
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Kentucky
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Massachusetts
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Michigan
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Wirral

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

Ethics approval
Ethics application status

Summary
Brief summary
A Phase III, Randomized, Open-Label, Controlled, Multi-Center, Global Study of First-Line
MEDI4736 (Durvalumab) Monotherapy and MEDI4736 (Durvalumab) in Combination with Tremelimumab
Versus Standard of Care Chemotherapy in Patients with Stage IV Urothelial Cancer
Trial website
https://clinicaltrials.gov/show/NCT02516241
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
Other publications