A Phase 3 trial of perioperative pembrolizumab for cisplatin-ineligible patients with MIBC
- Conditions
- Muscle-invasive Bladder Cancer (MIBC)MedDRA version: 21.1Level: LLTClassification code 10022877Term: Invasive bladder cancerSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-003809-26-GB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 610
-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%
*Urothelial carcinomas not originating from the bladder (eg, upper tract [ureters, renal pelvis], urethra) are not eligible
*Participants whose tumors contain any neuroendocrine component are not eligible
-Have clinically non-metastatic bladder cancer (N0M0) determined by imaging (CT chest and CT or MRI of the abdomen/pelvis), confirmed by BICR
-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
-Be ineligible for treatment with cisplatin, as defined by meeting at least one of the following criteria:
*Impaired renal function with measured or calculated CrCl 30 to 59 mL/min (calculated by Cockcroft-Gault method or measured by 24-hour urine collection)
*ECOG Performance Status 2
*CTCAE v.4 Grade =2 audiometric hearing loss (25 dB in two consecutive wave ranges))
*CTCAE v.4 Grade =2 peripheral neuropathy
*NYHA Class III heart failure
-Have a transurethral resection (TUR) of a bladder tumor (obtained within 60 days prior to study enrollment [ICF signed]) which is submitted and adequate for evaluation of histology, muscle invasion and PD-L1 status. In the event the sample is not evaluable for PD-L1, the participant will be assigned to the CPS <10 group for stratification.
Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides
-Must have an ECOG performance status of 0, 1, or 2
-Demonstrate adequate organ function (all screening labs should be performed within 14 days prior to randomization)
-Participant is male or female at least 18 years of age, at the time of signing the informed consent
-A male participant must agree to use contraception during the treatment period and for at least 120 days after the last dose of study treatment and refrain from donating sperm during this period
-A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies:
*Not a woman of childbearing potential (WOCBP) or
*A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 120 days after study interventions
-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: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 305
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 305
-Has a known additional non-urothelial malignancy that is progressing or has required active treatment =3 years of study randomization
-Has received any prior systemic anti-neoplastic treatment for MIBC
-Has an abdomino-pelvic lymph node =15 mm in the short axis
-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)
-Has received prior systemic anti-cancer therapy including investigational agents within 3 years prior to randomization
-Has received any prior radiotherapy to the bladder
-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, Bacillus Calmette-Guérin (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
-Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention
-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
-Has hypersensitivity to monoclonal antibodies (including pembrolizumab) and/or any of their excipients
-Has an active autoimmune disease that has required systemic treatment in past 2 years (ie, use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed
-Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
-Has an active infection requiring systemic therapy. Participant may be rescreened once after resolution of the infection
-Has a known history of human immunodeficiency virus (HIV) infection. No HIV testing is required unless mandated by local health authority
-Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as detectable HCV RNA via qualitative nucleic acid testing) infection
-Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator
-Has a known psychiatric or substance abuse disorder that would interfere with the participant’s ability to cooperate with the requirements of the study
-Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study intervention
-Has had an allogenic tissue/solid organ transplant
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