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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03374488
Recruitment Status : Active, not recruiting
First Posted : December 15, 2017
Results First Posted : August 28, 2019
Last Update Posted : August 28, 2019
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Incyte Corporation

Tracking Information
First Submitted Date  ICMJE December 11, 2017
First Posted Date  ICMJE December 15, 2017
Results First Submitted Date  ICMJE July 26, 2019
Results First Posted Date  ICMJE August 28, 2019
Last Update Posted Date August 28, 2019
Actual Study Start Date  ICMJE December 22, 2017
Actual Primary Completion Date July 27, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 14, 2019)
Objective Response Rate (ORR) With Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo [ Time Frame: up to 9 weeks +14 days ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: December 11, 2017)
  • Overall survival (OS) with pembrolizumab + epacadostat versus pembrolizumab + placebo [ Time Frame: Up to 27 months ]
    Defined as the time from the date of randomization to the date of death due to any cause.
  • Progression-free survival (PFS) with pembrolizumab + epacadostat versus pembrolizumab + placebo [ Time Frame: Up to 27 months ]
    Defined as the time from the date of randomization until disease progression per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by investigator determination, or death from any cause, whichever occurs first.
Change History Complete list of historical versions of study NCT03374488 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 14, 2019)
  • Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo as Measured by Number of Participants Experiencing Adverse Events (AEs) [ Time Frame: Up to 8 months ]
    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.
  • Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo as Measured by Number of Participants Discontinuing Study Treatment Due to AE [ Time Frame: Up to 8 months ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 11, 2017)
  • Objective response rate with pembrolizumab + epacadostat versus pembrolizumab + placebo [ Time Frame: Approximately 24 months ]
    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.
  • Number of participants experiencing adverse events (AEs) compared between pembrolizumab + epacadostat versus pembrolizumab + placebo [Safety and Tolerability] [ Time Frame: Up to 27 months ]
    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.
  • 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 ]
    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.
  • Mean change from baseline in global health status/quality of life scales [ Time Frame: Up to 25 months ]
    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).
  • Time to true deterioration (TTD) [ Time Frame: Up to 25 months ]
    Defined as the time from baseline to first onset of patient-reported outcome (PRO) deterioration.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pembrolizumab + Epacadostat vs Pembrolizumab + Placebo in Recurrent or Progressive Metastatic Urothelial Carcinoma
Official Title  ICMJE 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)
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Masking Description:
The study will be unblinded after the last participant completes Week 9 imaging assessment for efficacy analysis and after appropriate EC/IRB approvals have been received.
Primary Purpose: Treatment
Condition  ICMJE UC (Urothelial Cancer)
Intervention  ICMJE
  • Drug: Pembrolizumab
    Pembrolizumab administered intravenously Day 1 of each cycle every 3 weeks.
    Other Name: MK-3475
  • Drug: Epacadostat
    Epacadostat administered orally twice daily.
    Other Name: INCB024360
  • Drug: Placebo
    Matching placebo administered orally twice daily.
Study Arms  ICMJE
  • Experimental: Pembrolizumab 200 mg + Epacadostat 100 mg BID
    Pembrolizumab + epacadostat
    Interventions:
    • Drug: Pembrolizumab
    • Drug: Epacadostat
  • Active Comparator: Pembrolizumab 200 mg + placebo BID
    Pembrolizumab + placebo
    Interventions:
    • Drug: Pembrolizumab
    • Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: August 13, 2018)
84
Original Estimated Enrollment  ICMJE
 (submitted: December 11, 2017)
648
Estimated Study Completion Date  ICMJE August 2020
Actual Primary Completion Date July 27, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States,   Australia,   Canada,   Denmark,   France,   Germany,   Hungary,   Ireland,   Israel,   Italy,   Japan,   Korea, Republic of,   Netherlands,   Russian Federation,   Spain,   Taiwan,   Turkey,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03374488
Other Study ID Numbers  ICMJE KEYNOTE-698/ECHO-303
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Incyte Corporation
Study Sponsor  ICMJE Incyte Corporation
Collaborators  ICMJE Merck Sharp & Dohme Corp.
Investigators  ICMJE
Study Director: Mark Jones, MD Incyte Corporation
PRS Account Incyte Corporation
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP