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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03374488




Registration number
NCT03374488
Ethics application status
Date submitted
11/12/2017
Date registered
15/12/2017
Date last updated
28/08/2019

Titles & IDs
Public title
Pembrolizumab + Epacadostat vs Pembrolizumab + Placebo in Recurrent or Progressive Metastatic Urothelial Carcinoma
Scientific title
A Phase 3 Randomized, Double-Blind Clinical Study of Pembrolizumab + Epacadostat vs Pembrolizumab + Placebo as a Treatment for Recurrent or Progressive Metastatic Urothelial Carcinoma in Patients Who Have Failed a First-Line Platinum-containing Chemotherapy Regimen for Advanced/Metastatic Disease (KEYNOTE-698/ECHO-303)
Secondary ID [1] 0 0
KEYNOTE-698/ECHO-303
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
UC (Urothelial Cancer) 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney
Cancer 0 0 0 0
Bladder - transitional cell cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Pembrolizumab
Treatment: Drugs - Epacadostat
Treatment: Drugs - Placebo

Experimental: Pembrolizumab 200 mg + Epacadostat 100 mg BID - Pembrolizumab + epacadostat

Active Comparator: Pembrolizumab 200 mg + placebo BID - Pembrolizumab + placebo


Treatment: Drugs: Pembrolizumab
Pembrolizumab administered intravenously Day 1 of each cycle every 3 weeks.

Treatment: Drugs: Epacadostat
Epacadostat administered orally twice daily.

Treatment: Drugs: Placebo
Matching placebo administered orally twice daily.

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

Outcomes
Primary outcome [1] 0 0
Objective Response Rate (ORR) With Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo - ORR was defined as the percentage of participants who had a complete response (CR), disappearance of all target lesions or partial response (PR), >=30% decrease in the sum of the longest diameter of target lesions per RECIST v1.1 by investigator determination.
Timepoint [1] 0 0
up to 9 weeks +14 days
Secondary outcome [1] 0 0
Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo as Measured by Number of Participants Experiencing Adverse Events (AEs) - AE is defined as any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment.
Timepoint [1] 0 0
Up to 8 months
Secondary outcome [2] 0 0
Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo as Measured by Number of Participants Discontinuing Study Treatment Due to AE - AE is defined as any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment.
Timepoint [2] 0 0
Up to 8 months

Eligibility
Key inclusion criteria
- Histologically-confirmed diagnosis of urothelial carcinoma of the renal pelvis,
ureter, bladder, or urethra, that is transitional cell, or mixed
transitional/non-transitional (predominantly transitional) cell type.

- Progression or recurrence of urothelial carcinoma following one prior platinum
containing chemotherapy regimen for metastatic or unresectable locally advanced
disease. A participant who receives a neoadjuvant or adjuvant platinum-containing
regimen following cystectomy for localized muscle-invasive urothelial carcinoma is
acceptable (without further systemic treatment), if recurrence/progression occurs = 12
months following completion of therapy.

- Measurable disease based on RECIST v1.1.

- Have provided an archival tumor tissue sample or newly obtained core or excisional
biopsy of a tumor lesion not previously irradiated for PD-L1 analysis.

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

- Adequate organ function per protocol-defined criteria.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Urothelial carcinoma that is suitable for local therapy with curative intent.

- History or presence of an abnormal electrocardiogram (ECG) that, in the investigator's
opinion, is clinically meaningful.

- Known additional malignancy that is progressing or has required active treatment
within the past 3 years.

- Known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
Participants with previously treated brain metastases may participate provided they
are radiologically stable, ie, without evidence of progression for at least 4 weeks by
repeat imaging.

- Active autoimmune disease that has required systemic treatment in past 2 years.

- Known history of human immunodeficiency virus (HIV) infection. HIV testing is not
required unless mandated by local health authority.

- Known history of or is positive for active hepatitis B (HBsAg reactive) or has active
hepatitis C (HCV RNA). Note: Testing must be performed to determine eligibility.

- Use of protocol-defined prior/concomitant therapy.

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)
NSW,VIC
Recruitment hospital [1] 0 0
Southern Medical Day Care Centre - Wollongong
Recruitment hospital [2] 0 0
Austin Health-Austin Hospital - Heidelberg
Recruitment hospital [3] 0 0
Adelaide Cancer Centre - Kurralta Park
Recruitment hospital [4] 0 0
Macquarie University Hospital - Macquarie Park
Recruitment postcode(s) [1] 0 0
2500 - Wollongong
Recruitment postcode(s) [2] 0 0
3084 - Heidelberg
Recruitment postcode(s) [3] 0 0
5037 - Kurralta Park
Recruitment postcode(s) [4] 0 0
2109 - Macquarie Park
Recruitment outside Australia
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United States of America
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Arizona
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Plymouth
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Sunderland

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Incyte Corporation
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Merck Sharp & Dohme Corp.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study was to evaluate the efficacy and safety of pembrolizumab +
epacadostat vs pembrolizumab + placebo as a treatment for recurrent or progressive metastatic
urothelial carcinoma in patients who have failed a first-line platinum-containing
chemotherapy regimen for advanced/metastatic disease.
Trial website
https://clinicaltrials.gov/show/NCT03374488
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Mark Jones, MD
Address 0 0
Incyte Corporation
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