Phase 3 Study of Pembrolizumab with and without Epacadostat as a second treatment after a platinum containing chemotherapy for recurring or metastatic bladder cancer
- Conditions
- Recurrent or Progressive Metastatic Urothelial CarcinomaMedDRA version: 20.0Level: LLTClassification code 10064467Term: Urothelial carcinomaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2017-002310-31-IT
- Lead Sponsor
- INCYTE CORPORATIO
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 648
1. Have histologically-confirmed diagnosis of UC of the renal pelvis, ureter, bladder, or urethra, that is transitional cell, or mixed transitional/non-transitional (predominantly transitional) cell type.
2. Have progression or recurrence of UC following one prior platinum containing chemotherapy regimen for metastatic or unresectable locally advanced disease. No additional lines of systemic treatment are allowed.
3. Have the presence of at least one measurable lesion by computed tomography (CT) or Magnetic Resonance Imaging (MRI) per RECIST 1.1 as determined by the investigator/local radiology assessment.
a. If participants have only 1 measurable lesion per RECIST 1.1, any biopsy specimen should be obtained from the non-target lesion or archival tissue.
b. If participants have only 1 measurable lesion per RECIST 1.1, this lesion should not have been in the field of prior irradiation unless there is documented progression of the lesion(s).
4. 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. A newly obtained biopsy is strongly preferred but not required if archival tissue is adequate for analysis. If submitting unstained cut slides, freshly cut slides should be submitted to the central laboratory within 14 days from when the slides are cut. Refer to Section 9.8.1 in the protocol for an explanation. PD-L1 status (CPS =10 or CPS <10) must be determined by the central laboratory prior to randomization. Participants will be excluded if PD-L1 status cannot be determined.
5. Have resolution of all toxicities and any toxic effect(s) of the most recent prior therapy to Grade 1 or less (except alopecia). Participants with =Grade 2 neuropathy are an exception and may enroll.
6. Be =18 years of age on day of signing informed consent.
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 within 14 days prior to randomization.
Male participants:
8. A male participant must agree to use a contraception during the treatment period and for at least 120 days after the last dose of study treatment and refrain from donating sperm during this period.
Female participants:
A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
a.) Not a woman of childbearing potential (WOCBP)
OR
b.) A WOCBP who agrees to use contraception during the treatment period and for at least 120 days (corresponding to time needed to eliminate any study treatments (MK-3475 and epacadostat) after the last dose of study treatment.
9. The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
10. Have adequate organ function as defined in the protocol. Specimens must be collected within 14 days prior to randomization.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 259
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 389
1.Has urothelial carcinom that is suitable for local ther with curative intent.2.Has a gastrointest cndtion that in the opin of the Investigator may affect drug absorption.3.Has clinically signif cardiac disease,includ unstable angina,acute myocardial infarction within6months fromDay1 of study drug administr,or NY Heart Associat ClassIIIorIV cngestive heart failure.Medically cntrolled arhythmia stable on medication is xmitted.4.Has a history or presence of an abnormal ECG that,in the investigator's opin,is clinically meaningful.Screening corrected QT interval>480 msec is excluded(corrected by Fridericia or Bazett formula).In the event that a single QTc is >480 millisecnds,the participant may enroll if the average QTc for the3ECGs is <480 millisecnds.5.Has a history or current evidence of any cndition,ther,or lab abnormality that might cnfound the results of the study,interfere with the participant's particip for the full duration of the study,or is not in the best interest of the participant to particip,in the opin of the treating investigator.6.Has a diagnosis of immunodefic or is receiving chronic systemic steroid ther(in dosing>10mg daily of prednisone equival)or any other form of immunosupp ther within7days prior the first dose of study treatm.7.Has a known additional malignancy that is progressing or has required active treatm within the past3years.8.Has known active CNS metastases and/or carcinomtous meningitis.Participants with previously treated brain metastases may particip provided they are radiologically stable,clinically stable and w/o requirement of steroid treatm for at least14days prior to first dose of study treatm.9.Has severe hyxsensitivity(=Grade 3)to study treatm(pembrolizumab and epacadostat)and/or any of its excipients.10.Has an active autoimmune disease that has required systemic treatm in past2years.Replacement ther is not cnsidered a form of systemic treatm and is allowed.11.Has known history of or is positive for active HepatitisB or has active HepatitisC(HCV RNA).12.Has a history of(nn-infectious)pneumonitis that required steroids or has current pneumonitis.13.Has an active infection requiring systemic ther.14.Has a known history of human HIV infection.HIV testing is not required unless mandated by local health authority.15.Has known psychiatric or substance abuse disorders that would interfere with cooxating with the requirements of the study.16.A WOCBP who has a positive urine pregnancy test within72hours before randomization.If the urine test is positive or cannot be cnfirmed as negative,a serum pregnancy test will be required.17.Has received prior ther with an anti-PD-1,anti-PD-L1,anti PD-L2agent,IDO1 inhibitor,or with an agent directed to another stimulatory or co-inhibitory T-cell recept,or any other abs or drug targeting T-cell costimulatory pathways in the adjuvant or advanced/metastatic setting.18.Has received prior systemic anti-cancer ther includ investigational agents within4weeks prior to randomization.19.Has received prior radiother within2weeks of randomization.Participants must have recovered from all radiation-related toxicities(toGrade=1),and not require corticosteroids.A1-week washout is xmitted for palliative radiation(=2 weeks of radiother)to nn-CNS disease.20.Has received a live vaccine within30days prior to the first dose of study treatm. 21.Has received ther with a MAOI,melatonin supplement,or UGT1A9 inhibitor within21days prior to starting treatm,or anticipates requiring one of these
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method