A Phase 3, Randomized, Double-blind, Placebo-controlled Clinical Trial to Study the Efficacy and Safety of Pembrolizumab (MK-3475) in Combination With Chemoradiotherapy (CRT) Versus CRT Alone in Participants With Muscle-invasive Bladder Cancer (MIBC) (KEYNOTE-992)
概览
- 阶段
- 3 期
- 干预措施
- Pembrolizumab
- 疾病 / 适应症
- Urinary Bladder Neoplasms
- 发起方
- Merck Sharp & Dohme LLC
- 入组人数
- 520
- 试验地点
- 269
- 主要终点
- Bladder Intact Event-Free Survival (BI-EFS)
- 状态
- 进行中（未招募）
- 最后更新
- 昨天
概览
简要总结
Researchers are looking for new ways to treat muscle-invasive bladder cancer (MIBC). MIBC is a type of cancer that has not spread from the muscles in the bladder to other parts of the body.
MIBC is treated by having surgery to remove the bladder (cystectomy). Not all people choose to have surgery and want to keep their bladder using other treatments.
Chemoradiotherapy (CRT)- is a type of non-surgical treatment for MIBC which combines Chemotherapy (a treatment with medicine to destroy cancer cells or stop them growing) and Radiation therapy (a treatment that uses beams of intense energy [like X-rays] to shrink or get rid of tumors).
Pembrolizumab is an immunotherapy, which is a treatment that helps the immune system fight cancer.
A placebo looks like the study medicine but has no study medicine in it. Using a placebo helps researchers better understand if the study medicine works.
The goal of this study is to learn: 1. If a study medicine pembrolizumab given with Chemoradiotherapy (CRT) can help people live longer without their cancer growing, spreading, or coming back compared to placebo given with CRT. 2. About the safety and how well people tolerate CRT alone or in combination with pembrolizumab.
研究者
入排标准
入选标准
- •Has a histologically confirmed initial diagnosis of muscle-invasive bladder cancer (MIBC) with predominant urothelial histology
- •Has clinically nonmetastatic bladder cancer (N0M0)
- •Has planned and is eligible to receive chemoradiotherapy (CRT) and one of the protocol-specified radiosensitizing chemotherapy regimens
- •Has Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
- •Demonstrates adequate organ function
- •Male participants are eligible to participate if they agree to the following during the intervention period and for at least 90 days after the last dose of CRT treatment:
- •Refrain from donating sperm
- •Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent; or must agree to use contraception unless confirmed to be azoospermic
- •A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
- •Is not a woman of childbearing potential (WOCBP)
排除标准
- •Has the presence of diffuse carcinoma in situ (CIS) (multiple foci of CIS) throughout the bladder
- •Has the presence of urothelial carcinoma (UC) at any site outside of the urinary bladder in the previous 2 years except for Ta stage/T1 stage/CIS of the upper tract if the participant has undergone a complete nephroureterectomy
- •Has a known additional malignancy that is progressing or has required active therapy within the past 3 years, except basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer or other carcinoma in situ that has undergone potentially curative therapy
- •Has the presence of bilateral hydronephrosis
- •Has limited bladder function with frequency of small amounts of urine (\< 30 mL), urinary incontinence, or requires self-catheterization or a permanent indwelling catheter
- •Has received prior pelvic/local radiation therapy for any reason or any antineoplastic treatment for muscle-invasive bladder cancer (MIBC). Treatment for non-muscle invasive bladder cancer (NMIBC) with intravesical instillation therapy that was completed ≥28 days prior to randomization is allowed. Prior systemic treatment of NMIBC is not permitted.
- •Received prior therapy with an anti-PD-1 (programmed cell death protein 1), anti-PD-L1 (programmed death-ligand 1), or anti-PD-L2 (programmed cell death 1 ligand 2), or with an agent directed to another stimulatory or coinhibitory T-cell receptor (e.g., CTLA-4 \[cytotoxic T-lymphocyte-associated protein 4\], OX 40, or CD137 \[cluster of differentiation 137\])
- •Has received a live vaccine within 30 days before the first dose of study medication
- •Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study medication
- •Has known severe hypersensitivity (≥Grade 3) to the selected chemotherapy regimen, and/or any of their excipients and excipients of pembrolizumab
研究组 & 干预措施
Pembrolizumab + Chemotherapy + Radiotherapy
Participants receive pembrolizumab plus one of three chemotherapy regimens chosen by investigator, plus one of three radiotherapy regimens chosen by investigator.
干预措施: Pembrolizumab
Pembrolizumab + Chemotherapy + Radiotherapy
Participants receive pembrolizumab plus one of three chemotherapy regimens chosen by investigator, plus one of three radiotherapy regimens chosen by investigator.
干预措施: Cisplatin
Pembrolizumab + Chemotherapy + Radiotherapy
Participants receive pembrolizumab plus one of three chemotherapy regimens chosen by investigator, plus one of three radiotherapy regimens chosen by investigator.
干预措施: Mitomycin C (MMC)
Pembrolizumab + Chemotherapy + Radiotherapy
Participants receive pembrolizumab plus one of three chemotherapy regimens chosen by investigator, plus one of three radiotherapy regimens chosen by investigator.
干预措施: Gemcitabine
Placebo + Chemotherapy + Radiotherapy
Participants receive placebo to pembrolizumab plus one of three chemotherapy regimens chosen by investigator, plus one of three radiotherapy regimens chosen by investigator.
干预措施: Cisplatin
Placebo + Chemotherapy + Radiotherapy
Participants receive placebo to pembrolizumab plus one of three chemotherapy regimens chosen by investigator, plus one of three radiotherapy regimens chosen by investigator.
干预措施: Fluorouracil (5-FU)
Pembrolizumab + Chemotherapy + Radiotherapy
Participants receive pembrolizumab plus one of three chemotherapy regimens chosen by investigator, plus one of three radiotherapy regimens chosen by investigator.
干预措施: Conventional Radiotherapy (Bladder and pelvic nodes)
Pembrolizumab + Chemotherapy + Radiotherapy
Participants receive pembrolizumab plus one of three chemotherapy regimens chosen by investigator, plus one of three radiotherapy regimens chosen by investigator.
干预措施: Hypofractionated Radiotherapy (Bladder only)
Pembrolizumab + Chemotherapy + Radiotherapy
Participants receive pembrolizumab plus one of three chemotherapy regimens chosen by investigator, plus one of three radiotherapy regimens chosen by investigator.
干预措施: Fluorouracil (5-FU)
Placebo + Chemotherapy + Radiotherapy
Participants receive placebo to pembrolizumab plus one of three chemotherapy regimens chosen by investigator, plus one of three radiotherapy regimens chosen by investigator.
干预措施: Conventional Radiotherapy (Bladder only)
Placebo + Chemotherapy + Radiotherapy
Participants receive placebo to pembrolizumab plus one of three chemotherapy regimens chosen by investigator, plus one of three radiotherapy regimens chosen by investigator.
干预措施: Hypofractionated Radiotherapy (Bladder only)
Placebo + Chemotherapy + Radiotherapy
Participants receive placebo to pembrolizumab plus one of three chemotherapy regimens chosen by investigator, plus one of three radiotherapy regimens chosen by investigator.
干预措施: Placebo to Pembrolizumab
Pembrolizumab + Chemotherapy + Radiotherapy
Participants receive pembrolizumab plus one of three chemotherapy regimens chosen by investigator, plus one of three radiotherapy regimens chosen by investigator.
干预措施: Conventional Radiotherapy (Bladder only)
Placebo + Chemotherapy + Radiotherapy
Participants receive placebo to pembrolizumab plus one of three chemotherapy regimens chosen by investigator, plus one of three radiotherapy regimens chosen by investigator.
干预措施: Conventional Radiotherapy (Bladder and pelvic nodes)
Placebo + Chemotherapy + Radiotherapy
Participants receive placebo to pembrolizumab plus one of three chemotherapy regimens chosen by investigator, plus one of three radiotherapy regimens chosen by investigator.
干预措施: Mitomycin C (MMC)
Placebo + Chemotherapy + Radiotherapy
Participants receive placebo to pembrolizumab plus one of three chemotherapy regimens chosen by investigator, plus one of three radiotherapy regimens chosen by investigator.
干预措施: Gemcitabine
结局指标
主要结局
Bladder Intact Event-Free Survival (BI-EFS)
时间窗: Up to approximately 76 months
BI-EFS is defined as the time from randomization to any of the following events: residual/recurrent MIBC post-chemoradiotherapy (CRT), nodal or distant metastases as assessed by computerized tomography (CT) and CT urography (CTU) or magnetic resonance urography (MRU) per blinded independent central review (BICR) and/or biopsy results assessed by central pathology review, radical cystectomy, or death due to any cause. If biopsy is not feasible due to participant safety, the imaging alone will be sufficient. The BI-EFS for all participants will be presented.
次要结局
- Overall Survival (OS)(Up to approximately 95 months)
- Metastasis-Free Survival (MFS)(Up to approximately 95 months)
- Time to Occurrence of Non-Muscle-Invasive Bladder Cancer (NMIBC)(Up to approximately 95 months)
- Number of Participants Who Experienced an Adverse Event (AE)(Up to approximately 95 months)
- Number of Participants Who Discontinued Study Intervention Due to an AE(Up to approximately 1 year)
- Change from Baseline in the Global Health Status/Quality of Life (Items 29 and 30) Combined Score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)(Baseline and up to approximately 24 months)
- Change from Baseline in Physical Functioning (Items 1-5) Combined Score on the EORTC QLQ-C30(Baseline and up to approximately 24 months)
- Change from Baseline in the Visual Analog Score (VAS) of the European Quality of Life (EuroQoL)-5 Dimensions, 5-level Questionnaire (EQ-5D-5L)(Baseline and up to approximately 24 months)
- Change from Baseline in Urinary, Bowel, and Sexual Domains of the Bladder Cancer Index (BCI)(Baseline and up to approximately 24 months)
- Time to Deterioration (TTD) in the Global Health Status/Quality of Life (Items 29 and 30) Combined Score on the EORTC QLQ-C30(Up to approximately 24 months)
- TTD in Physical Functioning (Items 1-5) Combined Score on the EORTC QLQ-C30(Up to approximately 24 months)
- TTD in Urinary, Bowel, and Sexual Domains of the BCI(Up to approximately 24 months)
- TTD in the VAS of the EQ-5D-5L(Up to approximately 24 months)
- Time to Cystectomy(Up to approximately 95 months)
- Overall Survival (OS)(Up to approximately 7 years)
- Metastasis-Free Survival (MFS)(Up to approximately 7 years)
- Time to Occurrence of Non-Muscle-Invasive Bladder Cancer (NMIBC)(Up to approximately 7 years)
- Number of Participants Who Experienced an Adverse Event (AE)(Up to approximately 7 years)
- Change from Baseline in the Global Health Status/Quality of Life (Items 29 and 30) Combined Score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)(Baseline and up to approximately 2 years)
- Change from Baseline in Physical Functioning (Items 1-5) Combined Score on the EORTC QLQ-C30(Baseline and up to approximately 2 years)
- Change from Baseline in Urinary, Bowel, and Sexual Domains of the Bladder Cancer Index (BCI)(Baseline and up to approximately 2 years)
- Change from Baseline in the Visual Analog Score (VAS) of the European Quality of Life (EuroQoL)-5 Dimensions, 5-level Questionnaire (EQ-5D-5L)(Baseline and up to approximately 2 years)
- Time to Cystectomy(Up to approximately 7 years)