A Phase III Randomized, Controlled Clinical Trial of Pembrolizumab with or without Platinum-Based Combination Chemotherapy versus Chemotherapy in Subjects with Advanced or Metastatic Urothelial Carcinoma
- Conditions
- bladder cancerurothelial cancer10038364
- Registration Number
- NL-OMON45288
- Lead Sponsor
- Merck Sharp & Dohme (MSD)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 20
1. Have a histologically or cytologically confirmed diagnosis of advanced/unresectable or metastatic urothelial carcinoma of the renal pelvis, ureter [upper urinary tract], bladder, or urethra. Both transitional cell and mixed transitional/nontransitional cell histologies are allowed, but transitional cell carcinoma must be the predominant histology.;2. Have measurable disease based on RECIST 1.1 as determined by the local site investigator/radiology assessment. Target lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.;3. Voluntarily agree to participate by providing written informed consent/assent for the trial. The subject may also provide consent for Future Biomedical Research. However, the subject may participate in the main trial without participating in Future Biomedical Research.;4. Be >=18 years of age on the day of signing informed consent.;5. Have received no prior systemic chemotherapy for advanced or metastatic urothelial carcinoma, with the following exceptions:;a. Neoadjuvant platinum-based chemotherapy with recurrence >12 months from completion of therapy is permitted.;b. Adjuvant platinum-based chemotherapy following radical cystectomy with recurrence >12 months from completion of therapy is permitted.;6. Have provided tissue for biomarker analysis from an archival tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated from a muscle invasive urothelial carcinoma or a metastatic biopsy, originating from the origingal tumor. A newly obtained biopsy is strongly preferred but not required if archival tissue is evaluable. If submitting unstained cut slides, freshly cut slides should be submitted to the testing laboratory within 14 days from when the slides are cut. Refer to section 7.1.2.12 in the protocol for an explanation. PD-L1 status (CPS >10%) must be determined by the central laboratory during the screening period prior enrollment. ;7. Have an ECOG PS of 0, 1, or 2.;8. Demonstrate adequate organ function as defined in the protocol;9. Female subjects of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of trial medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.;10. Female subjects of childbearing potential must be willing to use an adequate method of contraception for the course of the trial through 120 days after the last dose of pembrolizumab or 180 days after chemotherapy treatment.;11. Male subjects of childbearing potential (section 5.7.2) must agree to use an adequate method of contraception as outlined in Section 5.2.7 - Contraception, starting with the first dose of trial therapy through 120 days after the last dose of pembrolizumab or 180 days after chemotherapy
1. Has disease that is suitable for local therapy administered with curative intent.;2. Is currently participating and receiving study therapy.;3. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to randomization.;4. Has an active autoimmune disease that has required systemic treatment in the past 2 years.;5. Has had a prior anti-cancer mAb for direct anti-neoplastic treatment within 4 weeks prior to the first dose of trial treatment (6 weeks for nitrosoureas or mitomycin C) or who has not recovered (ie, <=Grade 1 or at baseline) from AEs due to mAbs administered more than 4 weeks earlier. ;6. Has not recovered from AEs due to a previously administered agent.;7. Has a known additional malignancy that is progressing or requires active treatment within the past 5 years.;8. Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.;9. Has a known history of active tuberculosis (TB) (Bacillus tuberculosis).;10. Has an active infection requiring systemic therapy.;11. Has a history of severe hypersensitivity reaction to pembrolizumab, gemcitabine, carboplatin, or cisplatin or their analogs, and / or to any their excipients.;12. 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.;13. Has known psychiatric or substance abuse disorders.;14. Is pregnant or breastfeeding, or expecting to conceive or father children.;15. Has received prior therapy with an anti-PD-1, or anti-PD-L1, or anti-PD-L2 agent.;16. Has a known history of human immunodeficiency virus.;17. Has known active hepatitis B /C.;18. Has received a live virus vaccine within 30 days of planned start of trial therapy.;19. Has known active CNS metastases and/or carcinomatous meningitis.;20. Has symptomatic ascites or pleural effusion.;21. Has had a prior allogeneic stem cell or bone marrow transplant.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary endpoints will be progression-free survival (PFS) for compbo vs<br /><br>chemo only in the all-subject population using a blinded independent central<br /><br>review (BICR) and RECIST 1.1 to determine disease progression and overal<br /><br>survival (OS) for combo vs chemo only in the all-subject population and OS for<br /><br>pembro only vs chemo only in the PD-L1 CPS for both the PD-L1 CPS > 10% and<br /><br>all-subject population.</p><br>
- Secondary Outcome Measures
Name Time Method <p>Secondary endpoints will include objective response rates (ORR) and duration of<br /><br>response (DOR) using BICR and RECIST 1.1 to determine disease progression, for<br /><br>both the PD-L1 positive population and the all-subject population. The<br /><br>proportion of subjects who are progression free at specific time points will<br /><br>also be assessed. Exploratory endpoints include health-related quality of life<br /><br>as assessed by the European Organisation for Research and Treatment of Cancer<br /><br>Quality of Life Questionnaire (EORTC QLQ-C30) and European Quality of Life<br /><br>(EuroQol) EQ-5D*, as well as the relationship between genetic variations and<br /><br>response to treatment.</p><br>