Clinical Trials /

Pembrolizumab + Epacadostat vs Pembrolizumab + Placebo in Recurrent or Progressive Metastatic Urothelial Carcinoma

NCT03374488

Description:

The purpose of this study is 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.

Related Conditions:
  • Urothelial Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Pembrolizumab + Epacadostat vs Pembrolizumab + Placebo in Recurrent or Progressive Metastatic Urothelial Carcinoma
  • Official 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)

Clinical Trial IDs

  • ORG STUDY ID: 698-00/ECHO-303
  • NCT ID: NCT03374488

Conditions

  • Recurrent or Progressive Metastatic Urothelial Carcinoma

Interventions

DrugSynonymsArms
PembrolizumabMK-3475Treatment Group 1
EpacadostatINCB024360Treatment Group 1
PlaceboTreatment Group 2

Purpose

The purpose of this study is 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 Arms

NameTypeDescriptionInterventions
Treatment Group 1ExperimentalPembrolizumab + epacadostat
  • Pembrolizumab
  • Epacadostat
Treatment Group 2Active ComparatorPembrolizumab + placebo
  • Pembrolizumab
  • Placebo

Eligibility Criteria

        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.

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall survival (OS) with pembrolizumab + epacadostat versus pembrolizumab + placebo
Time Frame:Up to 27 months
Safety Issue:
Description:Defined as the time from the date of randomization to the date of death due to any cause.

Secondary Outcome Measures

Measure:Objective response rate with pembrolizumab + epacadostat versus pembrolizumab + placebo
Time Frame:Approximately 24 months
Safety Issue:
Description:Defined as the proportion of participants who have a best response of complete response (CR) or partial response (PR) per RECIST v1.1 by investigator determination.
Measure:Number of participants experiencing adverse events (AEs) compared between pembrolizumab + epacadostat versus pembrolizumab + placebo [Safety and Tolerability]
Time Frame:Up to 27 months
Safety Issue:
Description: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.
Measure:Number of participants discontinuing study treatment due to AEs compared between pembrolizumab + epacadostat versus pembrolizumab + placebo [Safety and Tolerability]
Time Frame:Up to 27 months
Safety Issue:
Description: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.
Measure:Mean change from baseline in global health status/quality of life scales
Time Frame:Up to 25 months
Safety Issue:
Description:Global health status/quality of life scales of the European Organisation for Research and Treatment of Cancer quality of life questionnaire (EORTC-QLQ)-C30 (items 29 and 30).
Measure:Time to true deterioration (TTD)
Time Frame:Up to 25 months
Safety Issue:
Description:Defined as the time from baseline to first onset of patient-reported outcome (PRO) deterioration.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Incyte Corporation

Trial Keywords

  • Urothelial carcinoma
  • programmed cell death protein 1 (PD-1) inhibitor
  • indoleamine 2,3-dioxygenase (IDO) inhibitor

Last Updated

January 10, 2018