advanced/unresectable (inoperable) or metastatic urothelial cancer of the renal pelvis, ureter, bladder, or urethra. MedDRA version: 17.1 Level: LLT Classification code 10046714 Term: Urothelial carcinoma bladder System Organ Class: 100000004864
Conditions
Interventions
Sponsors
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1-Be willing and able to provide written informed consent/assent for the trial. The subject may also provide consent/assent for Future Biomedical Research. However, the subject may participate in the main trial without participating in Future Biomedical Research. 2-Be ? 18 years of age on day of signing informed consent. 3. Have histologically or cytologically-confirmed diagnosis of advanced/unresectable (inoperable) or metastatic urothelial cancer of the renal pelvis, ureter, bladder, or urethra. Both transitional cell and mixed transitional/non-transitional cell histologies are allowed. Subjects with non-urothelial cancer of the urinary tract are not allowed. 4-Be considered cisplatin-ineligible to receive cisplatin-based combination therapy, based on having at least one of the following criteria: a-ECOG performance status of 2 (the proportion of ECOG 2 subjects will be limited to approximately 50% of the total population) b. Creatinine clearance (calculated or measured) 12 months from completion of therapy is permitted b-Neoadjuvant platinum based chemotherapy, with recurrence > 12 months since completion of therapy is permitted. 6-Have provided tissue for biomarker analysis from a newly obtained core or excisional biopsy of a tumor lesion not previously irradiated (mandatory). Adequacy of the biopsy specimen for PD-L1 biomarker analysis must be confirmed by the central laboratory. 7-Have measureable disease based on RECIST 1.1 as determined by central review. Tumor lesions situated in a previously irradiated area are considered measureable if progression has been demonstrated in such lesions. 8-Have a performance status of 0, 1 or 2 on the ECOG Performance Scale, as assessed within 10 days prior to treatment initiation. 9-Demonstrate adequate organ function as defined in Table 1. All screening labs should be performed within 10 days of treatment initiation. 10-Female subject of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. 11-Female subjects of childbearing potential must be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication (Reference Section 5.7.2). Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for >1 year. 12-Male subjects must agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy. 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 250 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 100
Exclusion criteria
Exclusion criteria: 1-Has disease that is suitable for local therapy administered with curative intent. 2-Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks prior to the first dose of treatment. 3-Has had a prior anti-cancer monoclonal antibody (mAb) for direct anti-neoplastic treatment within 4 weeks prior to study Day 1 or who has not recovered (i.e., ? Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier. 4-Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ? Grade 1 or at baseline) from adverse events due to a previously administered agent. 5-Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer. A history of prostate cancer that was identified incidentally following cystoprostatectomy for bladder cancer is acceptable, provided that the following criteria are met: stage T2N0M0 or lower; and Gleason score ? 6, and undetectable PSA. 6-Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable [without evidence of progression by imaging (confirmed by CT scan if CT used at prior imaging, or confirmed by MRI if MRI was used at prior imaging) for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline], have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability. 7-Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. 8-Has evidence of interstitial lung disease or active non-infectious pneumonitis. 9-Has an active infection requiring systemic therapy. 10-Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject´s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. 11-Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. 12-Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment. 13-Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or with an agent directed to another co-inhibitory T-cell receptor (e.g. CTLA-4, OX-40, CD137). 14-Has a known history of Human Immunodeficiency Virus (HIV) (HIV-1/2 antibodies). 15-Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g.,
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1.Objective: To evaluate anti-tumor activity of pembrolizumab (MK-3475) as 1L therapy in subjects with advanced/unresectable (inoperable) or metastatic urothelial cancer who are ineligible for cisplatin-based therapy and whose tumors express PD-L1 protein (IHC), by overall response rate (ORR) based on RECIST 1.1 as assessed by independent radiology review.;Secondary Objective: 1-To investigate the association between PD-L1 protein expression by immunohistochemistry and anti-tumor activity of pembrolizumab (MK-3475) as 1L therapy and establish a cut-point for PD-L1 positive status if this is not determined by another study in subjects with advanced/unresectable (inoperable) or metastatic urothelial cancer who are ineligible for cisplatin-based therapy. 2-To evaluate anti-tumor activity of pembrolizumab (MK-3475) as 1L therapy in subjects with advanced/unresectable (inoperable) or metastatic urothelial cancer who are ineligible for cisplatin-based therapy, by ORR based on RECIST 1.1 as assessed by independent radiology review. (Read rest in the protocol);Primary end point(s): To evaluate anti-tumor activity of pembrolizumab (MK-3475) as 1L therapy in subjects with advanced/unresectable (inoperable) or metastatic urothelial cancer who are ineligible for cisplatin-based therapy and whose tumors express PD-L1 protein (IHC), by overall response rate (ORR) based on RECIST 1.1 as assessed by independent radiology review.;Timepoint(s) of evaluation of this end point: The primary efficacy endpoint is overall response rate, defined as the proportion of subjects in the analysis population who have complete response (CR) or partial response (PR) using RECIST 1.1 criteria assessed by independent radiology review at any time during the study. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Objective: To investigate the association between PD-L1 protein expression by immunohistochemistry and anti-tumor activity of pembrolizumab (MK-3475) as 1L therapy and establish a cut-point for PD-L1 positive status if this is not determined by another study in subjects with advanced/unresectable (inoperable) or metastatic urothelial cancer who are ineligible for cisplatin-based therapy. 2. Objective: To evaluate anti-tumor activity of pembrolizumab (MK-3475) as 1L therapy in subjects with advanced/unresectable (inoperable) or metastatic urothelial cancer who are ineligible for cisplatin-based therapy, by ORR based on RECIST 1.1 as assessed by independent radiology review. 3. Objective: To evaluate anti-tumor activity of pembrolizumab (MK-3475) as 1L therapy in subjects with advanced/unresectable (inoperable) or metastatic urothelial cancer who are ineligible for cisplatin-based therapy, by ORR based on modified RECIST 1.1 as assessed by independent radiology review, in all subjects and PD-L1 positive subjects. 4. Objective: To evaluate the anti-tumor activity of pembrolizumab (MK-3475) as 1L therapy in subjects with advanced/unresectable (inoperable) or metastatic urothelial cancer who are ineligible for cisplatin-based therapy, by ORR based on RECIST 1.1 as assessed by the study site radiology review, in all subjects and PD-L1 positive subjects. 5. Objective: To evaluate the anti-tumor activity of pembrolizumab (MK-3475) as 1L therapy in subjects with advanced/unresectable (inoperable) or metastatic urothelial cancer who are ineligible for cisplatin-based therapy, by progression-free survival (PFS) based on RECIST 1.1 as assessed by independent radiology review, in all subjects and PD-L1 positive subjects. 6. Objective: To evaluate the anti-tumor activity of pembrolizumab (MK-3475) as 1L therapy in subjects with advanced/unresectable (inoperable) or metastatic urothelial cancer who are ineligible for cisplatin-based therapy, by p | — |
Countries
Australia, Canada, Denmark, Hungary, Ireland, Israel, Italy, Netherlands, Puerto Rico, Spain, United Kingdom, United States
Contacts
Public ContactInvestigación Clínica
Merck Sharp & Dohme de España S.A.
Outcome results
None listed