Phase 3 Study of First-line Pembrolizumab With or Without Lenvatinib in Urothelial Carcinoma in Cisplatin-ineligible Participants Whose Tumors Express PD-L1 and Participants Ineligible for Any Platinum-containing Chemotherapy.
- Conditions
- Advanced/unresectable or metastatic urothelial carcinomaTherapeutic area: Diseases [C] - Cancer [C04]MedDRA version: 20.0Level: LLTClassification code 10064467Term: Urothelial carcinomaSystem Organ Class: 100000004864
- Registration Number
- EUCTR2018-003752-21-IT
- Lead Sponsor
- MERCK SHARP & DOHME CORP. UNA SUSSIDIARIA DI MERCK & CO. INC.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 694
1Hav histologic or cytologic conf diagnosis of advan/unresectable or metastatic urothelial carc renal pelvis,ureter,bladder,urethra.Both transitio cell and mix transitio/nontransitio cell hist are allow,but transitio cellcarc must be predom hist
2Hav least 1meas target lesion RECIST1.1assess local site investig/radiol, per followcriteria:1lymph node lesion measuring>=15mm short axis2)nonnodal lesion measuring >=10 mmlongest diameter3)lesion suitable frepeat measurement with CT/MRI imaging.Lesion
previously irradiat area consid measurable progres has been demonstrated in such lesions
3Hav provid archival tumor tissue sample or newly obtain core or excisional biopsy tumor lesion not previously irrad and adequatePDL1evaluat.Formalinfix, paraffembedd tissue blocks are prefer slides. Newly obtained biopsies are prefer archiv tissue.PDL1 status(CPS>=10orCPS <10)must obtain by centlab dur screening perd prior enrollm
4Hav receiv no prior systemic chemo for advan or metastaticUCwith follow except
-Neoadjuvant platinumbas chemoth for treatment muscleinvasive bladder cancer with recurrenc>12months from completion of the therapy is permit
-Adjuvant platinumbas chemoth follow radical cystectomy,with recurrence>12 months from completion,is permit
5Meet criteria for either option or option b: aHav tumor withPDL1CPS>=1andcons ineligible receive cisplatinbas combin ther,bas on 1 follow
-ECOG PS 2 within7day prior trandom
-CrCl(calculat or measur using institut standard)>=30to<=60mL/min
-NCICTCAEVers4.0 Grade>=2 audiometric hearing loss
-NCICTCAEVers4.0 Grade>=2 peripheral neuropathy
OR
bopinion invest,be cons ineligible receive any platinumbas chemoth(ineligible for cisplatin and carboplatin)bas on
-ECOGPS2within7day prior random and least1of follow
-Docum visceral metastatic dis
-CrCl>=30 to<=60 mL/min
-NCICTCAE Version 4.0 Grade>=2 audiom hear loss
-NCICTCAE Version 4.0 Grade>=2 peripheral neuropathy
-Other reason,identif case report form,for part being unable receive both cisplatin and carboplatin safely.Add criteria for platinum ineligibility will be considered and allowed on a casebycase basis,follow consult Sponsor
6male or female>=18 years age and consider an adult per local regulations on day of signing the inform consent
7HavECOGPS01or2within7dayprior random and life expectancy of>=3 months
8Male particip are eligible participate if agree follow dur interven perd and for least3dayafter last dose of pembro or lenvatinib/placebo:
-Be abstinent heterosexual interc their prefer and usual lifestyle and agree remain abstinent
OR
-Must agree use contracep unless confirm be azoospermic as detail below:
-Agree use male condom plus partner use addit contraceptive method when hav penilevaginal intercourse with WOCBP who isnot currently pregnant
9female part eligible to participate if she isnot pregnant or breastfeeding and at least one of followcond applies:
-Isnot a WOCBP
OR
-IsWOCBP and using contraceptive method that is highly effective with low user dependency, or be abstinent from heterosexual intercourse as her preferred and usual lifestyle,dur intervperd and for least 120days post pembro orn30 days post lenvatinib/placebo
-WOCBPmust hav negative highly sensitive pregnancy test within 24hours before first dose study interven
-urine test cannot be conf as negative, a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive
-investitor iresponsible review omedical
1Has disease that is suitable local ther adminis with curative intent
2Has tumor with any neuroendocrine or small cell comp
3Has history of gastroint cond or proc(gastric bypass,malabsorption)that,opinion investig,may affect oral drug absorption
4Has had major surgery within 3 week prior first dose of stu interv
5Has a prexisting Grade>=3 gastrointestinal or nongastroint fistula
6Has radiographic evidence of major blood vessel invasion/infiltration, or has had clinically significant hemoptysis (at least 0.5 teaspoon of bright red blood) or tumor bleeding within2week prior first dose of stu interv
7Has had signif cardiov impairment within12month first dose stu interv
8Has known intolerance or severe hypers(Grade>=3)pembro or lenvatinib or any of their excipients
9Has receiv lenvatinib monoth or combin withPD1/PDL1 inhibitor or has previously been enroll clinical stu evaluating lenvatinib for bladder cancer, regardless treatm receiv
10Is WOCBP who positive urine pregnancy test within 24 hours before random
11Has receiv prior therapy with an antiPD1,antiPDL1,or antiPDL2inhibitor,indoleaminepyrrole2,3 dioxygenase(IDO1)inhibitor or agent directed to another stimulatory or coinhibitory Tcell rec(CTLA4,OX40,CD137)or any other antibody or drug targeting T-cell costimulatory pathways adjuvant or advanc/metastatic sett
12Has receiv prior radioth metastatic site without use of chemoth radiosens within3weeks first dose stu interv,with excep palliative radioth bone lesions, which is allow if complet2weeks before start stu interve.Particip must have recov from all radiationrelat toxicities, and must not require corticosteroids
13Has receiv live vaccine within30day prior first dose stu interv
14investigator’s judgment, has not recover from toxicity or other compl from any major surgery prior to starting stu interven
15Is currently particip in or has partic trial of investig agent or has use investig device within4weeks prior first dose of stu intervention
16Has anLVEFbelow institutional normal range, as determMUGAorECHO
17Has history or presence abnormal ECG that,investigr opinion, is clinically meaningful
18Has diagnosis immunodef or is receiv systemic steroid therapy (dose exceeding 10 mg daily of prednisone equivalent) or any other form of immunosupp ther within7days prior random
19Has had an active malignancy(except locally advanced or metastaticUC) within the past 36 months
20Has central nervous system(CNS)metastases, unless the participant has completed local therapy and has discontinued use of corticosteroids for this indication for at least 4 weeks before starting treatment in this stu.Any signs or symptoms of CNS metastases must be stable for at least 4 weeks before starting stu intervention
21Has an active autoimmune disease that has required systemic treatment in the past 2 years.
22Has a history of (non-infectious) pneumonitis that required systemic steroids, or current pneumonitis
23Has an active infec requiring systemic therapy
24Has known history of human immunod virus (HIV) infection
25Has known history of or is positive for active hepatitisB or has active hepatitisC
26Has active tuberculosis
27Has history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the stu, interfere with the participant’s participation for the full duration of the stu, or is not in the best interest of the participant to participate, in the opinion of the treating investigator
28Has known psychiatric or
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