Bladder Cancer
Conditions
Keywords
Programmed Cell Death-1 (PD1, PD-1), Programmed Death-Ligand 1 (PDL1, PD-L1), Pembrolizumab (MK-3475), Chemotherapy
Brief summary
A global study to evaluate peri-operative pembrolizumab with chemotherapy versus placebo to pembrolizumab plus chemotherapy in cisplatin eligible patients.
Interventions
DRUGPembrolizumab
Pembrolizumab 200 mg by intravenous (IV) infusion, given on Day 1 of each 21-day cycle
DRUGGemcitabine
Gemcitabine 1000 mg/m\^2, IV infusion on Days 1 and 8 of each 21-day cycle
DRUGCisplatin
Cisplatin 70 mg/m\^2, IV infusion on Day 1 of each 21-day cycle
Surgical RC+PLND will be done in accordance with the American Urological Association (AUA)/American Society of Clinical Oncology (ASCO)/American Society for Radiation Oncology (ASTRO)/Society of Urologic Oncology (SUO) guidelines.
DRUGPlacebo
Placebo to pembrolizumab by IV infusion, given on Day 1 of each 21-day cycle
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double-blind
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have a histologically confirmed diagnosis of urothelial carcinoma (UC) / muscle invasive bladder cancer (MIBC) (T2-T4aN0M0 or T1-T4aN1M0) with predominant (≥50%) urothelial histology. * Have clinically non-metastatic bladder cancer (N≤1 M0) determined by imaging (computed tomography (CT) or magnetic resonance imaging (MRI)) of the chest/abdomen/pelvis. * Be deemed eligible for Radical Cystectomy (RC) + Pelvic Lymph Node Dissection (PLND). * Have Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1. * Have adequate organ function. * Male and female participants are eligible to participate if they agree to the contraception use as per study protocol.
Exclusion criteria
* Has a known additional malignancy that is progressing or has required active anti-cancer treatment ≤3 years of study randomization with certain exceptions. * Has received any prior systemic treatment for MIBC or non-invasive muscle bladder cancer (NMIBC - prior treatment for NMIBC with intravesical BCG/chemotherapy is permitted) or prior therapy with an anti- programmed cell death 1 (PD-1), anti-programmed cell death ligand 1/ ligand 2 (PD-L1/L2), or anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). * Has ≥N2 disease or metastatic disease (M1) as identified by imaging. * Is cisplatin-ineligible, as defined by meeting any one of the cisplatin ineligibility criteria as per protocol. * Has received prior systemic anticancer therapy including investigational agents within 3 years of randomization or any radiotherapy to the bladder. * Has undergone partial cystectomy of the bladder to remove any NMIBC or MIBC. * Has received a live or live attenuated vaccine within 30 days before the first dose of study intervention. * Has a diagnosis of immunodeficiency or has a known history of human immunodeficiency virus (HIV) infection, Hepatitis B infection or known active Hepatitis C infection. * Has a known psychiatric or substance abuse disorder. * Has had an allogenic tissue/solid organ transplant.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Event-Free Survival (EFS) | Up to approximately 60 months | EFS is defined as the time from randomization to the first occurrence of any of the following events: progression of disease that precludes RC surgery; failure to undergo RC surgery in participants with residual disease and any radiographical disease present; gross residual disease left behind at the time of surgery; local or distant recurrence based on investigator assessments and/or biopsy, or death due to any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pathologic Complete Response (pCR) Rate | Up to approximately 72 months | pCR rate is defined as the percentage of participants having pCR. pCR is defined as absence of viable tumor (pT0N0) in examined tissue from RC and PLND, as assessed by blinded independent central review (BICR). |
| Overall Survival (OS) | Up to approximately 72 months | Overall survival is defined as the time from randomization to death due to any cause. |
| Disease-Free Survival (DFS) | From approximately 20 weeks up to approximately 72 months | DFS is defined as the time from post-surgery baseline scan until the first occurrence of either local or distant recurrence as assessed by investigator by CT or MRI and/or computerized tomography (CT) or magnetic resonance imaging (MRI) and or biopsy or death from any cause. |
| Pathologic Downstaging (pDS) Rate | Up to approximately 72 months | pDS rate is defined as the percentage of participants having pDS. pDS is defined as participants with a tumor classification of \<pT2 (includes pT0, pTis, pTa, pT1) and N0 in examined tissue from RC plus PLND as assessed by BICR. |
| Number of Participants Who Experienced an Adverse Event (AE) | Up to approximately 72 months | An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. |
| Number of Participants Who Discontinued Study Treatment Due to an AE | Up to approximately 12 months | An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. |
| Number of Participants Who Experienced Perioperative Complications | Up to approximately 12 months | An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. |
| Change in Patient-Reported Outcomes from Baseline in Total Score of Functional Assessment of Cancer Therapy - General (FACT-G) | Baseline, Up to approximately 72 months | The FACT-G is a health-related quality of life (HRQoL) 27-item questionnaire in patients being treated for cancer. The FACT-G subscales include Physical Well-Being (PWB), Social/Family Well-Being (SWB), Emotional Well-Being (EWB), and Functional Well-Being (FWB). All items are scored on a 5-point Likert scale of 0 to 4, with higher scores indicating higher HRQoL. The total score can range from 0 to 108. |
| Change in Patient-Reported Outcomes from Baseline in Total Score of FACT-Bladder- (FACT-BI-Cys) | Baseline, Up to approximately 72 months | Total Score of FACT BI-Cys is the sum of FACT-G total score and FACT-Bl-Cys score. FACT-Bl-Cys contains 17 items on the bowel, bladder, and sexual symptoms following cystectomy. The FACT-G is a health-related quality of life (HRQoL) 27-item questionnaire in patients being treated for cancer. The FACT-G subscales include Physical Well-Being (PWB), Social/Family Well-Being (SWB), Emotional Well-Being (EWB), and Functional Well-Being (FWB). All items are scored on a 5-point Likert scale of 0 to 4, with higher scores indicating higher HRQoL. The total score of FACT-Bl-Cys can range from 0 to 168. |
| Change in Patient-Reported Outcomes from Baseline in FACT-BI-Cys-Trial Outcome Index (TOI) | Baseline, Up to approximately 72 months | FACT-Bl-Cys Trial Outcome Index (TOI) is the sum of FACT-G PWB score, FWB score, and FACT-Bl-Cys score. FACT-Bl-Cys contains 17 items on the bowel, bladder, and sexual symptoms following cystectomy. The FACT-G is a health-related quality of life (HRQoL) 27-item questionnaire in patients being treated for cancer. The FACT-G subscales include Physical Well-Being (PWB), Social/Family Well-Being (SWB), Emotional Well-Being (EWB), and Functional Well-Being (FWB). All items are scored on a 5-point Likert scale of 0 to 4, with higher scores indicating higher HRQoL. The total score of FACT-Bl-Cys TOI can range from 0 to 116. |
| Change in Patient-Reported Outcomes from Baseline in EuroQol Five-Dimensional Questionnaire (EQ-5D-5L) Visual Analog Score (VAS) | Baseline, Up to approximately 72 months | The EQ-5D-5L is a standardized instrument for use as a measure of health outcome. In the EQ-5D-5L VAS, the participant rates his or her general state of health at the time of the assessment on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state. |
| Time to Deterioration (TTD) in the Total Score of FACT-G | Up to approximately 72 months | The FACT-G is a health-related quality of life (HRQoL) 27-item questionnaire in patients being treated for cancer. The FACT-G subscales include Physical Well-Being (PWB), Social/Family Well-Being (SWB), Emotional Well-Being (EWB), and Functional Well-Being (FWB). All items are scored on a 5-point Likert scale of 0-4, with higher scores indicating higher HRQoL. TTD is defined as the time from baseline to the first onset of patient-reported outcomes (PRO) deterioration. For the FACT-G questionnaire, deteriorations are defined as a decrease of 7 points or more (out of 108) from baseline in total score. |
| TTD in EQ-5D-5L VAS | Up to approximately 72 months | The EQ-5D-5L is a standardized instrument for use as a measure of health outcome and includes 5 health state dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. In the EQ-5D-5L VAS, the participant rates his or her general state of health at the time of the assessment on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state. TTD is defined as the time from baseline to the first onset of PRO deterioration. For the EQ 5D-5L, deterioration is defined as a decrease of 7 points or more from baseline in the VAS. |
Countries
Australia, Belgium, Canada, Denmark, France, Germany, Hungary, Ireland, Israel, Italy, Japan, Mexico, Poland, Russia, South Korea, Spain, Sweden, Thailand, Turkey (Türkiye), Ukraine, United Kingdom, United States
Contacts
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Outcome results
None listed