A phase II study investigating use of the drug MPDL3280A before surgery in bladder cancer patients

Phase 1

• Conditions: T2-T4N0M0 transitional cell carcinoma of the bladder; MedDRA version: 19.0Level: PTClassification code 10066752Term: Bladder transitional cell carcinoma stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 19.0Level: PTClassification code 10066754Term: Bladder transitional cell carcinoma stage IIISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 19.0Level: PTClassification code 10066753Term: Bladder transitional cell carcinoma stage IISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2015-001112-35-DE
• Lead Sponsor: Queen Mary University of London

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2016-04-22
• Last Update Posted: 8 January 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 85

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 (surgical opinion, cystoscopy or radiological presence).
-Fit and planned for cystectomy (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 [<1% per year] when used consistently and correctly) and to continue its use for 90 days after the last dose of MPDL3280A.
-Adequate hematologic and end-organ function within 4 weeks prior to the first study treatment defined by the following:
a) ANC = 1500 cells/µL (without granulocyte colony-stimulating factor support within 2 weeks prior to Cycle 1, Day 1)
b) WBC counts > 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 55
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30

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, anti-CTLA-4, anti-programmed death-1 (PD-1), or anti-PD-L1 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 half-lives 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 prostate-specific 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), drug-induced 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 [anti-HBc] antibody test) are eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified