- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03212651
Study Evaluating Neoadjuvant Pembrolizumab Monotherapy in Patients With Muscle-Invasive Bladder Cancer to Explore in Vivo the Mechanisms of Action of Pembrolizumab (PANDORE)
January 19, 2023 updated by: Gustave Roussy, Cancer Campus, Grand Paris
A Phase II Study Evaluating Neoadjuvant Pembrolizumab Monotherapy in Patients With Muscle-Invasive Bladder Cancer to Explore in Vivo the Mechanisms of Action of Pembrolizumab
monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2; Recent phase I trial provided evidence of activity of pembrolizumab in advanced platinum-resistant metastatic urothelial carcinoma; Recent phase 3 trial showed an overall survival benefit in patients treated with pembrolizumab in a trial comparing pembrolizumab to chemotherapy in patients who failed first-line platinum-based chemotherapy Neoadjuvant chemotherapy followed by radical cystectomy is the standard of care for cisplatinum-eligible non-metastatic MIBC patients; Many patients with MIBC are unfit for cisplatin-based combination treatment; Given its safety profile, pembrolizumab may be used in unfit patients; Neo-adjuvant setting is a unique opportunity to assess mechanisms of action of pembrolizumab in human
Study Overview
Study Type
Interventional
Enrollment (Actual)
41
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Val De Marne
-
Villejuif, Val De Marne, France, 94805
- Gustave Roussy
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Be willing and able to provide written informed consent for the trial.
- Be >/= 18 years of age on day of signing informed consent.
- Histologically confirmed muscle invasive transitional cell carcinoma of the bladder (Note: urothelial carcinoma invading into the prostatic stroma with no histologic muscle invasion is allowed, provided that the extent of disease is confirmed via imaging and/or EUA. Patients with mixed histologies are required to have a dominant transitional cell pattern)
- Clinical stage T2-T4a N0/X M0 disease according to TNM classification (within 4 weeks before registration)
- Medically appropriate candidate for radical cystectomy as per urologic oncologist
- Representative formalin-fixed paraffin embedded (FFPE) bladder tumor samples with an associated pathology report that are determined to be available and sufficient for central testing. If an insufficient amount of tumor tissue is available prior to the start of the screening phase, subjects must consent to allow the acquisition of additional tumor tissue for performance of central testing.
Patients who refuse neoadjuvant cisplatin based chemotherapy or in whom neoadjuvant cisplatin based therapy is not appropriate for the following conditions:
- ECOG performance status of 2
- Creatinine clearance (calculated according to MDRD formula or measured) less than 1mL/s
- CTCAE version 4.0, grade 2 or above audiometric hearing loss
- CTCAE version 4.0, grade 2 or above peripheral neuropathy
Adequate bone marrow function obtained within 14 days before registration
- Absolute neutrophil count ≥ 1,500/mm3
- Hb ≥9 g/dL or ≥5.6 mmol/L without transfusion or EPO dependency (within 7 days of assessment)
- Platelet count ≥ 100,000/mm3
Adequate organ function obtained within 14 days before registration
- Bilirubin ≤ 1.5 times upper limit of normal (ULN) or Direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULN
- Alkaline phosphatase ≤ 2 x upper limit of normal (ULN);
- AST and ALT ≤2.5 x upper limit of normal (ULN);
- Creatinine clearance > 30 ml/min according to MDRD formula
- Albumin >2.5 mg/dL
Adequate Coagulation function
- International Normalized ratio (INR) or Prothrombin Time (PT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
- Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
- Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 14 days prior to the first dose of study treatment. Both sexually active females and males (and their female partners) patients must agree to use two methods of highly effective contraception, one of them being a barrier method, or to abstain from sexual activity during the study and for at least 4 months after last study drug administration.
- Patient affiliated to a social security regimen or beneficiary of the same
Exclusion Criteria:
- Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks before the first dose of study treatment.
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of systemic immunosuppressive therapy within 7 days prior to the first dose of study treatment (except local/topical or aerosol steroids)
- Has a known history of active TB (Bacillus Tuberculosis)
- Hypersensitivity to pembrolizumab or any of its excipients
- Has had a prior monoclonal antibody within 4 weeks or 5 halflife time (whatever the shortest) prior to the first dose of study treatment or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
- Has had prior intra-venous chemotherapy, targeted small molecule therapy, or radiation therapy for bladder cancer
- Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
- Has an active autoimmune / immune mediated inflammatory disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjorgen's syndrome will not be excluded from the study.
- Has evidence of interstitial lung disease or active, non-infectious pneumonitis.
- Has an active infection requiring systemic therapy.
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
- Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
- Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
- Positive for Human Immunodeficiency Virus (HIV) antibody testing
- Active or chronic hepatitis C and/or B infection. Patients with past/resolved HBV infection (defined as the presence of antihepatitis B core antibody, IgG anti-HBs +) are eligible. HBV DNA should be obtained in these patients prior to the first dose of study treatment. Patients positive for HCV antibody are eligible only if PCR is negative for HCV RNA
- Has received a live attenuated vaccine within 30 days prior to the first dose of study treatment
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Patients with MIBC (Muscle Invasive Bladder Cancer)
Cisplatinum-ineligible patients with muscle-invasive bladder cancer
|
Pembrolizumab 200mg IV infusion
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Pathologic complete response rate
Time Frame: Up to 1 month
|
defined as the absence of carcinoma (pT0 disease) and the absence of microscopic lymph node metastases (N0) on the final cystectomy specimen in PD-L1 positive patients and PD-L1 negative patients
|
Up to 1 month
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
October 17, 2017
Primary Completion (Actual)
July 18, 2019
Study Completion (Actual)
December 13, 2019
Study Registration Dates
First Submitted
July 6, 2017
First Submitted That Met QC Criteria
July 6, 2017
First Posted (Actual)
July 11, 2017
Study Record Updates
Last Update Posted (Actual)
January 20, 2023
Last Update Submitted That Met QC Criteria
January 19, 2023
Last Verified
January 1, 2023
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2016-002537-29
- 2016/2432 (Other Identifier: CSET number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Undecided
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Bladder Cancer
-
University of Southern CaliforniaNational Cancer Institute (NCI)TerminatedStage III Bladder Cancer | No Evidence of Disease | Stage II Bladder Cancer | Stage IVA Bladder Cancer | Stage IVB Bladder CancerUnited States
-
H. Lee Moffitt Cancer Center and Research InstituteCompletedMuscle-Invasive Bladder Carcinoma | Bladder Cancer Stage II | Bladder Cancer Stage III | Bladder Cancer Stage IVUnited States
-
Case Comprehensive Cancer CenterNational Cancer Institute (NCI)WithdrawnRecurrent Bladder Cancer | Urinary Complications | Stage 0 Bladder Cancer | Stage I Bladder Cancer | Stage II Bladder Cancer
-
National Cancer Institute (NCI)CompletedStage III Bladder Cancer | Stage I Bladder Cancer | Stage II Bladder CancerUnited States
-
National Cancer Institute (NCI)TerminatedStage III Bladder Cancer | Stage IV Bladder Cancer | Recurrent Bladder Carcinoma | Bladder Adenocarcinoma | Bladder Squamous Cell Carcinoma | Bladder Urothelial Carcinoma | Stage I Bladder Cancer | Stage II Bladder CancerUnited States
-
Fox Chase Cancer CenterTerminatedStage III Bladder Cancer | Distal Urethral Cancer | Proximal Urethral Cancer | Squamous Cell Carcinoma of the Bladder | Urethral Cancer Associated With Invasive Bladder Cancer | Stage II Bladder CancerUnited States
-
University of WashingtonNational Cancer Institute (NCI)CompletedStage III Bladder Cancer | Stage IV Bladder Cancer | Recurrent Bladder Carcinoma | Stage II Bladder CancerUnited States
-
Academisch Medisch Centrum - Universiteit van Amsterdam...Bristol-Myers SquibbRecruitingUrinary Bladder Cancer | Invasive Bladder CancerNetherlands
-
Taris Biomedical LLCBristol-Myers SquibbTerminatedBladder Cancer TNM Staging Primary Tumor (T) T2 | Bladder Cancer TNM Staging Primary Tumor (T) T2A | Bladder Cancer TNM Staging Primary Tumor (T) T2B | Bladder Cancer TNM Staging Primary Tumor (T) T3 | Bladder Cancer TNM Staging Primary Tumor (T) T3A | Bladder Cancer TNM Staging Primary Tumor... and other conditionsUnited States
-
Baylor College of MedicinePfizerTerminatedBladder Cancer | Invasive Bladder Cancer | Metastatic Bladder CancerUnited States
Clinical Trials on Pembrolizumab
-
University Medical Center GroningenCompleted
-
Incyte CorporationMerck Sharp & Dohme LLCCompletedMelanomaUnited States, France, Italy, United Kingdom, Spain, Belgium, Israel, Mexico, Japan, Canada, Netherlands, Sweden, Korea, Republic of, Australia, Russian Federation, Chile, Germany, Poland, Ireland, New Zealand, Denmark, Switzerland, South Africa
-
Merck Sharp & Dohme LLCCompletedMelanomaAustralia, South Africa, Spain, Sweden
-
Acerta Pharma BVMerck Sharp & Dohme LLCCompletedMetastatic Urothelial CarcinomaUnited States
-
HUYABIO International, LLC.Active, not recruitingNon Small Cell Lung CancerUnited States
-
Prof. Dr. Matthias PreusserUnknownPrimary Central Nervous System LymphomaAustria
-
Yonsei UniversityNot yet recruitingMucosal Melanoma | Acral MelanomaKorea, Republic of
-
Academisch Medisch Centrum - Universiteit van Amsterdam...Merck Sharp & Dohme LLC; PTC TherapeuticsRecruitingColorectal Cancer | Endometrium CancerNetherlands
-
Michael BoyiadzisMerck Sharp & Dohme LLCCompletedAcute Myeloid LeukemiaUnited States