T2T4N0M0 transitional cell carcinoma of the bladder MedDRA version: 21.1 Level: PT Classification code 10066753 Term: Bladder transitional cell carcinoma stage II System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: PT Classification code 10066754 Term: Bladder transitional cell carcinoma stage III System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Lev
Conditions
Interventions
Product Name: MPDL3280A
Product Code: RO5541267
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: MPDL3280A
Other descriptive name: RO5541267
Concentration unit: mg/ml milligram(s)/milli
Sponsors
Queen Mary University of London
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: -Willing and able to provide written informed consent -Ability to comply with the protocol -Age = 18 years -Histopathologically confirmed transitional cell carcinoma (T2-T4a) of the bladder. Patients with mixed histologies are required to have a dominant transitional cell pattern. -Residual disease after TURBT or endoscopy (surgical opinion, cystoscopy or radiological presence). -Fit and planned for radical surgery (according to local guidelines). -N0 or M0 disease CT or MRI (within 4 weeks of registration) Representative formalin-fixed paraffin embedded (FFPE) bladder tumour samples with an associated pathology report that are determined to be available and sufficient for central testing. -Patients who refuse neoadjuvant cisplatin-based chemotherapy or in whom neoadjuvant cisplatin-based therapy is not appropriate. -Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 -Negative pregnancy test within 2 weeks of Day 1 Cycle 1 for female patients of childbearing potential. -For female patients of childbearing potential to use a highly effecting form(s) of contraception (i.e. one that results in a low failure rate [ 2500/µL c)Lymphocyte count = 500/µL d) Platelet count = 100,000/µL (without transfusion within 2 weeks prior to Cycle 1, Day 1) e) Haemoglobin = 9.0 g/dL (patients may be transfused or receive erythropoietic treatment to meet this criterion). f) AST or ALT, and alkaline phosphatase = 2.5 times the institutional upper limit of normal (ULN) (patients with known Gilbert disease who have serum bilirubin level = 3 × the institutional ULN may be enrolled). g) INR and aPTT = 1.5 × the institutional ULN. This applies only to patients who are not receiving therapeutic anticoagulation; patients receiving therapeutic anticoagulation should be on a stable dose. h) Calculated creatinine clearance = 20 mL/min (Cockcroft-Gault formula) 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 16 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 80
Exclusion criteria
Exclusion criteria: -Pregnant and lactating female patients -Major surgical procedure within 4 weeks prior to enrolment or anticipation of need for a major surgical procedure during the course of the study other than for diagnosis -Previous intravenous chemotherapy for bladder cancer -Patients with prior allogeneic stem cell or solid organ transplantation -Prior treatment with CD137 agonists, antiCTLA4, anti-programmed death-1 (PD1), or anti-PDL1 therapeutic antibody or pathway-targeting agents -Patients must not have had oral/IV steroids for 14 days prior to study entry. The use of inhaled corticosteroids, physiologic replacement doses of glucocorticoids and mineralocorticoids is allowed. -Received therapeutic oral or intravenous antibiotics within 2 weeks prior to enrolment. Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible -Administration of a live, attenuated vaccine within 4 weeks prior to enrolment or anticipation that such a live, attenuated vaccine will be required during the study -Treatment with systemic immunostimulatory agents (e.g. interferons or interleukin [IL]-2) within 4 weeks or five halflives of the drug, whichever is shorter, prior to enrolment -Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to enrolment -Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results, including significant liver disease (such as cirrhosis, uncontrolled major seizure disorder, or superior vena cava syndrome) -Malignancies other than UBC within 5 years prior to Cycle 1, Day 1, with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, or ductal carcinoma in situ treated surgically with curative intent) or localized prostate cancer treated with curative intent and absence of prostatespecific antigen (PSA) relapse or incidental prostate cancer (Gleason score = 3 + 4 and PSA < 10 ng/mL undergoing active surveillance and treatment naive) -Severe infections within 4 weeks prior to enrolment in the study (e.g. hospitalization for complications of infection, bacteraemia, severe pneumonia) -Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within 3 months prior to enrolment, unstable arrhythmias, or unstable angina -History of idiopathic pulmonary fibrosis (including pneumonitis), druginduced pneumonitis, organizing pneumonia (bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest CT scan (History of radiation pneumonitis in the radiation field (fibrosis) is permitted) -Patients with uncontrolled Type 1 diabetes mellitus. Patients with Type 1 diabetes controlled on a stable insulin regimen are eligible. -Patients with active hepatitis infection (positive hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C. Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (negative HBsAg test and a positive antibody to hepatitis B core antigen [antiHBc] antibody test) are eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine MPDL3280A's ability to reduce the size of bladder cancer before surgery (measured as pathological complete response rate), and assess the impact of the drug on the body's immune system.;Secondary Objective: The secondary objectives are as follows: - Assess the safety and tolerability of MPDL3280A in this patient population by collecting information about adverse events and surgical complications. - Assess the anti-tumour effect of MPDL3280A by examining the radiological response (looking at pre- and post-treatment MRI/CT scan images) and “disease free survival” rates. - Assess the effect of MPDL3280A on overall patient survival.;Primary end point(s): Clinical: Pathological complete response rate (pCRR) defined as =20% decrease in residual disease of the bladder, based on histological evaluation of the resected bladder specimen collected during cystectomy (post–treatment). Biological: Dynamic changes in T cell subpopulations (CD8 and/or CD3) measured in tumour samples collected pre and post treatment with MPDL3280A.;Timepoint(s) of evaluation of this end point: Clinical: pCR rate will be based on histological evaluation of the resected specimen collected during surgery (after 1-2 cycles of MPDL3280A treatment). Biological: The change in T cell expression will be measured in tumour biopsy samples collected before and after treatment with MPDL3280A (an archival sample and a sample taken at surgery or post-treatment biopsy). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Incidence, nature and severity of adverse events graded according to NCI-CTCAE v4.03 collected during and after MPDL3280A treatment. • Surgical complications as assessed by the Clavien-Dindo scoring system. • Radiological response, defined as a =30% decrease in tumour diameter from the baseline scan based on local investigator assessments • Disease-free survival, defined as time between the date of enrolment to first evidence of disease progression based on local investigator assessments or death, whichever occurs first. • Overall survival, defined as the time between the date of enrolment and death due to any cause. • In the upper tract cohort: o Pathological complete response rate (pCRR) defined as no microscopic evidence (pT0/Tis/Cis) of residual disease based on histological evaluation of the resected tumour specimen collected during surgery (post–treatment). o Dynamic changes in T cell subpopulations (CD8 and/or CD3) measured in tumour samples collected pre- and post-treatment. o RR is defined as a =30% decrease in tumour diameter from the baseline scan based on local investigator assessments. o DFS is defined as time between the date of enrolment to first evidence of relapse based on local investigator assessments or death, whichever occurs first. o OS is defined as the time between the date of enrolment and death due to any cause.;Timepoint(s) of evaluation of this end point: • Adverse events will be recorded during treatment and up to 24 weeks post-surgery (AEs are recorded up to 4 weeks post-surgery, and unresolved AEs monitored until resolved or until 24 weeks post-surgery). Surgical complications will be assessed by the Clavien-Dindo scoring system post-surgery. • Radiological response will be assessed before and after treatment with MPDL3280A (baseline and pre-surgery). • Disease free survival will be recorded from enrolment until first evidence of disease recurrence or death; patients are followed up for 2 years after sur | — |
Countries
France, Germany, Netherlands, Spain, United Kingdom
Contacts
Public ContactMays Jawad
Queen Mary University of London
Outcome results
None listed