Trial record 2 of 74 for:    MPDL3280A

Preoperative MPDL3280A in Transitional Cell Carcinoma of the Bladder (ABACUS)

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2016 by Queen Mary University of London
Sponsor:
Collaborator:
Roche Pharma AG
Information provided by (Responsible Party):
Queen Mary University of London
ClinicalTrials.gov Identifier:
NCT02662309
First received: January 18, 2016
Last updated: June 28, 2016
Last verified: June 2016
  Purpose
ABACUS is an open-label, international, multi-centre, window of opportunity phase II trial for patients with histologically confirmed (T2-T4a) transitional cell carcinoma of the bladder. The trial aims to test the efficacy of preoperative MPDL3280A and will include extensive biomarker work on samples from these patients. Eligible patients will receive two 3-weekly cycles of MPDL3280A pre-cystectomy. Following cystectomy, patients will be followed up for safety, survival, and disease data.

Condition Intervention Phase
Bladder Cancer
Drug: MPDL3280A
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study Investigating Preoperative MPDL3280A in Operable Transitional Cell Carcinoma of the Bladder (ABACUS)

Resource links provided by NLM:


Further study details as provided by Queen Mary University of London:

Primary Outcome Measures:
  • Efficacy of MPDL3280A pre-cystectomy with respect to pathological complete response rate (pCRR) [ Time Frame: 2-3 months (timeframe dependent on delay to surgery) ] [ Designated as safety issue: No ]
    Assessment based on pre-treatment tumour sample collected at screening (archival) and post-treatment tumour sample taken at cystectomy. Pathological complete response rate (pCRR) defined as ≥20% reduction in residual disease of the bladder based on histological evaluation of the resected bladder specimen collected during cystectomy (post-treatment).

  • Efficacy of MPDL3280A pre-cystectomy on immune parameters [ Time Frame: 2-3 months (timeframe dependent on delay to surgery) ] [ Designated as safety issue: No ]
    Dynamic changes in T cell subpopulations (CD8 and/or CD3) measured in tumour samples collected pre- and post-treatment.


Secondary Outcome Measures:
  • Safety and tolerability of MPDL3280A when given to this patient population pre-cystectomy [ Time Frame: Approx 34 weeks (from screening registration, throughout treatment and up to 24 weeks post-cystectomy - timeframe dependent on delay to surgery) ] [ Designated as safety issue: Yes ]
    Incidence, nature and severity of adverse events (AEs) and surgical complications will be reviewed.

  • Efficacy of MPDL3280A pre-cystectomy with respect to anti-tumour effects as measured by radiological response (RR) [ Time Frame: Approx 34 weeks (timeframe dependent on delay to pre-cystectomy visit) ] [ Designated as safety issue: No ]
    CT or MRI scan taken at screening and pre-cystectomy visits. RR is defined as a >30% decrease in tumour diameter from the baseline scan.

  • Efficacy of MPDL3280A pre-cystectomy with respect to anti-tumour effects based on disease free survival (DFS) [ Time Frame: Up to 2 years post-cystectomy ] [ Designated as safety issue: No ]
    Disease and survival data is reviewed at post-surgery visits and at 1 and 2 years post-cystectomy.

  • Efficacy of MPDL3280A pre-cystectomy with respect to anti-tumour effects based on overall survival (OS) [ Time Frame: Up to 2 years post-cystectomy ] [ Designated as safety issue: No ]
    Disease and survival data is reviewed at post-surgery visits and at 1 and 2 years post-cystectomy.


Estimated Enrollment: 85
Study Start Date: February 2016
Estimated Study Completion Date: March 2019
Estimated Primary Completion Date: March 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MPDL3280A
Patients receive 2x 3-weekly cycles of MPDL3280A (one infusion on the first day of each cycle) prior to cystectomy surgery.
Drug: MPDL3280A
Intravenous infusion
Other Name: Atezolizumab

Detailed Description:
MPDL3280A (also called atezolizumab) is an immune check point inhibitor which targets programmed death-ligand 1 (PD-L1). Overexpression of PD-L1 prevents the immune system from eradicating cancerous cells as it blocks antigen recognition. MPDL3280A inhibits this interaction, allowing immune-mediated tumour cell killing.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Willing and able to provide written informed consent
  2. Ability to comply with the protocol
  3. Age ≥ 18 years
  4. Histopathologically confirmed transitional cell carcinoma (T2-T4a) of the bladder. Patients with mixed histologies are required to have a dominant transitional cell pattern.
  5. Residual disease after TURBT (surgical opinion, cystoscopy or radiological presence).
  6. Fit and planned for cystectomy (according to local guidelines).
  7. N0 or M0 disease CT or MRI (within 4 weeks of registration)
  8. 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.
  9. Patients who refuse neoadjuvant cisplatin based chemotherapy or in whom neoadjuvant cisplatin based therapy is not appropriate.
  10. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
  11. Negative pregnancy test within 2 weeks of Day 1 Cycle 1 for female patients of childbearing potential.
  12. 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.
  13. Adequate hematologic and end-organ function within 4 weeks prior to the first study treatment defined by the following:

    • ANC ≥ 1500 cells/μL (without granulocyte colony-stimulating factor support within 2 weeks prior to Cycle 1, Day 1)
    • WBC counts > 2500/μL
    • Lymphocyte count ≥ 500/μL
    • Platelet count ≥ 100,000/μL (without transfusion within 2 weeks prior to Cycle 1, Day 1)
    • Haemoglobin ≥ 9.0 g/dL (patients may be transfused or receive erythropoietic treatment to meet this criterion).
    • 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).
    • 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.
    • Calculated creatinine clearance ≥ 20 mL/min (Cockcroft-Gault formula)

Exclusion Criteria:

  1. Pregnant and lactating female patients.
  2. 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.
  3. Previously intravenous chemotherapy for bladder cancer.
  4. Patients with prior allogeneic stem cell or solid organ transplantation.
  5. Prior treatment with CD137 agonists, anti-CTLA-4, anti−programmed death−1 (PD-1), or anti−PD-L1 therapeutic antibody or pathway-targeting agents.
  6. Patients must not have had oral or IV steroids for 14 days prior to study entry. The use of inhaled corticosteroids, physiologic replacement doses of glucocorticoids (i.e., for adrenal insufficiency), and mineralocorticoids (e.g., fludrocortisone) is allowed.
  7. Received therapeutic oral or intravenous (IV) antibiotics within 14 days prior to enrolment (Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible).
  8. 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.
  9. Treatment with systemic immunostimulatory agents (including but not limited to interferons or interleukin [IL]−2) within 4 weeks or five half-lives of the drug, whichever is shorter, prior to enrolment.
  10. Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 4 weeks prior to enrolment.
  11. 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).
  12. 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).
  13. Severe infections within 4 weeks prior to enrolment in the study including but not limited to hospitalization for complications of infection, bacteraemia, or severe pneumonia.
  14. 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.
  15. History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e., 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).
  16. Patients with uncontrolled Type 1 diabetes mellitus. Patients with Type 1 diabetes controlled on a stable insulin regimen are eligible.
  17. Patients with active hepatitis infection (defined as having a positive hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C. Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as having a 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 (PCR) is negative for HCV RNA.
  18. Positive test for HIV
  19. Patients with active tuberculosis
  20. History of gastrointestinal disorders (medical disorders or extensive surgery) which may interfere with the absorption of the study drug.
  21. Uncontrolled hypercalcemia (> 1.5 mmol/L ionized calcium or Ca > 12 mg/dL or corrected serum calcium > the institutional ULN) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab. Patients who are receiving bisphosphonate therapy or denosumab specifically to prevent skeletal events and who do not have a history of clinically significant hypercalcemia are eligible. Patients who are receiving denosumab prior to enrollment must be willing and eligible to receive a bisphosphonate instead while on study.
  22. History of autoimmune disease including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis.
  23. Patients with a history of autoimmune-related hypothyroidism, unless on a stable dose of thyroid-replacement hormone.
  24. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
  25. Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the MPDL3280A formulation
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02662309

Contacts
Contact: ABACUS Coordinator 020 7882 8275 bci-abacus@qmul.ac.uk

Locations
France
Centre Hospitalier Universitaire (CHU) de Bordeaux Not yet recruiting
Bordeaux, France
Principal Investigator: Alain Ravaud         
Hospices Civils de Lyon Not yet recruiting
Lyon, France
Principal Investigator: Denis Maillet         
Institut Paoli-Calmettes Not yet recruiting
Marseille, France
Principal Investigator: Gwenaëlle Gravis         
Institut Claudius Régaud Not yet recruiting
Toulouse, France
Principal Investigator: Christine Chevreau         
Germany
Universitätsklinik Köln Not yet recruiting
Cologne, Germany
Principal Investigator: Jan Herden         
Universitätsklinikum Düsseldorf Not yet recruiting
Düsseldorf, Germany
Principal Investigator: Anja Lorch         
Universitätsklinikum des Saarlandes Not yet recruiting
Homburg, Germany
Principal Investigator: Michael Stöckle         
Universitätsklinikum Schleswig-Holstein Not yet recruiting
Lübeck, Germany
Principal Investigator: Axel S Merseburger         
LMU: Urologische Klinik und Poliklinik Not yet recruiting
Munich, Germany
Principal Investigator: Michael Staehler         
Universitätsklinikum Tübingen Not yet recruiting
Tübingen, Germany
Principal Investigator: Jens Bedke         
Netherlands
Netherlands Cancer Institute (NKI) Not yet recruiting
Amsterdam, Netherlands
Principal Investigator: Michiel van der Heijden         
Spain
Hospital Germans Trias i Pujol Not yet recruiting
Barcelona, Spain
Contact       ap.abacus@apices.es   
Principal Investigator: Albert Font Pous         
Hospital del Mar Not yet recruiting
Barcelona, Spain
Contact       ap.abacus@apices.es   
Principal Investigator: Alejo Rodríguez-Vida Rodríguez         
Athaia Xarxa Manresa Not yet recruiting
Barcelona, Spain
Contact       ap.abacus@apices.es   
Principal Investigator: Montserrat Doménech Santasusana         
Hospital Santa Creu i Sant Pau Not yet recruiting
Barcelona, Spain
Contact       ap.abacus@apices.es   
Principal Investigator: José Pablo Maroto Rey         
Hospital Vall d'Hebron Not yet recruiting
Barcelona, Spain
Contact       ap.abacus@apices.es   
Principal Investigator: Cristina Suárez         
Hospital Reina Sofía Not yet recruiting
Córdoba, Spain
Contact       ap.abacus@apices.es   
Principal Investigator: José Méndez Vidal         
Hospital 12 de Octubre Not yet recruiting
Madrid, Spain
Contact       ap.abacus@apices.es   
Principal Investigator: Daniel Castellano Gauna         
CHU de Santiago Not yet recruiting
Santiago de Compostela, Spain
Contact       ap.abacus@apices.es   
Principal Investigator: Urbano Anido Herranz         
Hospital Virgen del Rocío Not yet recruiting
Seville, Spain
Contact       ap.abacus@apices.es   
Principal Investigator: Ignacio Durán Martínez         
United Kingdom
Cambridge University Hospitals NHS Trust Not yet recruiting
Cambridge, United Kingdom
Contact       bci-abacus@qmul.ac.uk   
Principal Investigator: Danish Mazhar         
Clatterbridge Cancer Centre NHS Foundation Trust Not yet recruiting
Liverpool, United Kingdom
Contact       bci-abacus@qmul.ac.uk   
Principal Investigator: Syed Hussain         
Barts Health NHS Trust Recruiting
London, United Kingdom
Contact       bci-abacus@qmul.ac.uk   
Principal Investigator: Thomas Powles         
University College London Hospitals NHS Foundation Trust Recruiting
London, United Kingdom
Contact       bci-abacus@qmul.ac.uk   
Principal Investigator: Mark Linch         
Oxford University Hospitals NHS Foundation Trust Recruiting
Oxford, United Kingdom
Contact       bci-abacus@qmul.ac.uk   
Principal Investigator: Andrew Protheroe         
Sheffield Teaching Hospitals NHS Foundation Trust Not yet recruiting
Sheffield, United Kingdom
Contact       bci-abacus@qmul.ac.uk   
Principal Investigator: Jim Catto         
University Hospital Southampton NHS Foundation Trust Recruiting
Southampton, United Kingdom
Contact       bci-abacus@qmul.ac.uk   
Principal Investigator: Simon Crabb         
Sponsors and Collaborators
Queen Mary University of London
Roche Pharma AG
Investigators
Principal Investigator: Thomas Powles, MBBS MD MRCP Queen Mary University of London
  More Information

Responsible Party: Queen Mary University of London
ClinicalTrials.gov Identifier: NCT02662309     History of Changes
Other Study ID Numbers: 010463QM  2015-001112-35 
Study First Received: January 18, 2016
Last Updated: June 28, 2016
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Queen Mary University of London:
Muscle invasive bladder cancer
Transitional cell carcinoma

Additional relevant MeSH terms:
Carcinoma
Urinary Bladder Neoplasms
Carcinoma, Transitional Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Urinary Bladder Diseases
Urologic Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 21, 2016