EUCTR2018-003808-39-FR进行中（未招募）1 期
A Phase 3, Randomized Double Blind Study to Evaluate Peri-operative Pembrolizumab (MK-3475) + Neoadjuvant Chemotherapy versus Perioperative Placebo + Neoadjuvant Chemotherapy in Cisplatin-Eligible Participants with Muscle-invasive Bladder Cancer (KEYNOTE-866)
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 790
研究概览
简要总结
暂无简介。
研究设计
- 研究类型
- Interventional clinical trial of medicinal product
入排标准
入选标准
- •To be eligible for inclusion in this study, the participant must:
- •1. Have a histologically confirmed diagnosis of muscle invasive bladder cancer (T2-T4aN0M0) with predominant (=50%) urothelial histology (histology and presence of muscle invasion to be confirmed by BICR):
- •- Participants with mixed histology are eligible provided the urothelial component is =50% as noted above.
- •- Participants whose tumors contain any neuroendocrine component are not eligible.
- •- Urothelial carcinomas not originating from the bladder (eg, upper tract [ureters, renal pelvis], urethra) are not eligible.
- •2. Have clinically non-metastatic bladder cancer (N0M0) determined by imaging (CT chest and CT or MRI of the abdomen/pelvis), confirmed by BICR.
- •3. Be deemed eligible for RC + PLND by his/her urologist and/or oncologist and agree to undergo curative intent standard RC + PLND (including prostatectomy if applicable) as per AUA/ASTRO/ASCO/SUO guidelines
- •4. Have a transurethral resection (TUR) of a bladder tumor (obtained within 60 days prior to enrollment [ICF signed]) that is submitted and adequate to determine histology, muscle invasion, and PD-L1 status by central pathology vendor. In the event the sample is not evaluable for PD-L1, the participant will be assigned to the CPS <10 group for stratification.
- •5. Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- •6. Have demonstrated adequate organ function (all screening labs should be performed within 14 days prior to randomization).
- •7. Participant is male or female and at least 18 years of age inclusive, at the time of signing the informed consent.
- •8. A male participant must agree to use contraception as detailed in Appendix 5 of this protocol during the treatment period and for at least 180 days (corresponding to time needed to eliminate any study treatment(s) [pembrolizumab and or any active combination] plus an additional 90 days [a spermatogenesis cycle] for study treatments where there is risk of clinically relevant genotoxicity) after the last dose of study treatment and refrain from donating sperm during this period.
- •9. A female participant is eligible to participate if she is not pregnant not breastfeeding, and at least 1 of the following conditions applies:
- •a. Not a woman of childbearing potential (WOCBP)
- •b. WOCBP who agrees to follow the contraceptive guidance:Contraceptive Guidance and Pregnancy Testing during the treatment period and for at least 180 days (corresponding to time needed to eliminate any study treatment(s) [pembrolizumab and or any active combination] plus 30 days [a menstruation cycle] for study treatments with risk of genotoxicity) after the last dose of study treatment.
- •10. The participant (or legally acceptable representative if applicable) provides written informed consent/assent for the study. The participant may also provide consent/assent for future biomedical research. However, the participant may participate in the main study without participating in future biomedical research.
- •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 237
排除标准
- •1. Has a known additional malignancy that is progressing or has required active anti-cancer treatment =3years of study randomization
- •2. Has received any prior systemic anti-neoplastic treatment for MIBC.
- •3. Has an abdomino-pelvic lymph node =15 mm in the short axis.
- •4. Is cisplatin-ineligible, as defined by meeting any one of the following criteria:
- •- Impaired renal function with measured or calculated creatinine clearance (CrCl) <60 mL/min (calculated by Cockcroft-Gault method or 24-hour urine collection).
- •- ECOG Performance Status = 2
- •- CTCAE v.4 Grade =2 audiometric hearing loss (threshold shift of >25 dB averaged at 2 consecutive test frequencies in at least 1 ear; testing is not required at screening; it may be performed at investigator’s discretion)
- •- CTCAE v.4 Grade =2 peripheral neuropathy
- •- New York Heart Association (NYHA) Class III heart failure
- •5. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137).
- •6. Has received therapy with hematopoietic growth factor such as granulocyte-colony stimulating factor (G-CSF) or GM-CSF in 14 days prior to randomization.
- •7. Has received prior systemic anti-cancer therapy including investigational agents within 3 years of randomization.
- •8. Has received any prior radiotherapy to the bladder.
- •9. Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, BCG, and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
- •10. Is currently participating in or has participated in a study of an investigational agent orhas used an investigational device within 4 weeks prior to the first dose of study intervention.
- •11. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug.
- •12. Has hypersensitivity to mAbs (including pembrolizumab) and/or any of their excipients.
- •13. Has severe hypersensitivity (=Grade 3) to cisplatin and/or gemcitabine and any of their excipients.
- •14. Has an active autoimmune disease that has required systemic treatment in past 2 years. Replacement therapy is not considered a form of systemic treatment and is allowed.
- •15. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
- •16. Has an active infection requiring systemic therapy. Participant may be rescreened once after resolution of the infection.
- •17. Has a known history of human immunodeficiency virus (HIV) infection. No HIV testing is required unless mandated by local health authority
- •18. Has a known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known
研究者
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