Preoperative MPDL3280A in Transitional Cell Carcinoma of the Bladder

NCT02662309 | Completed Phase 2 DMC

• 2 other identifiers: 010463QM2015-001112-35
• Study Type: interventional
• Target: 96
• Locations: 4 countries
• Sites: 20

Brief Summary

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.

Conditions

Bladder Cancer

Keywords

Muscle invasive bladder cancer; Transitional cell carcinoma

Outcome Measures

Primary Outcomes (1)

• Efficacy of MPDL3280A pre-cystectomy with respect to pathological complete response rate (pCRR)

  Pathological complete response rate defined as no microscopic evidence of residual disease in the bladder based on histological evaluation of the resected bladder specimen collected during cystectomy (post-treatment).

  2-3 months (timeframe dependent on delay to surgery)

Secondary Outcomes (3)

• Efficacy of MPDL3280A pre-cystectomy with respect to anti-tumour effects as measured by radiological response (RR)

  Approx 34 weeks (timeframe dependent on delay to pre-cystectomy visit)

• Efficacy of MPDL3280A pre-cystectomy with respect to anti-tumour effects based on disease free survival (DFS)

  Up to 2 years post-cystectomy

• Efficacy of MPDL3280A pre-cystectomy with respect to anti-tumour effects based on overall survival (OS)

  Up to 2 years post-cystectomy

Study Arms (1)

MPDL3280A

EXPERIMENTAL

Patients receive 2x 3-weekly cycles of MPDL3280A (one infusion on the first day of each cycle) prior to cystectomy surgery.

Drug: MPDL3280A

Interventions

MPDL3280A DRUG

Intravenous infusion

Also known as: Atezolizumab

MPDL3280A

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.
• Previously 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 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.
• 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).
• 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 (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.
• Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 4 weeks 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 including but not limited to hospitalization for complications of infection, bacteraemia, or 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 (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).

Sponsors & Collaborators

• Queen Mary University of London: lead
• Hoffmann-La Roche: collaborator

Study Sites (20)

Centre Hospitalier Universitaire (CHU) de Bordeaux

Bordeaux, France

Location

Hospices Civils de Lyon

Lyon, France

Location

Institut Paoli-Calmettes

Marseille, France

Location

Institut Claudius Régaud

Toulouse, France

Location

Netherlands Cancer Institute (NKI)

Amsterdam, Netherlands

Location

Athaia Xarxa Manresa

Barcelona, Spain

Location

Hospital del Mar

Barcelona, Spain

Location

Hospital Germans Trias i Pujol

Barcelona, Spain

Location

Hospital Santa Creu i Sant Pau

Barcelona, Spain

Location

Hospital Vall d'Hebron

Barcelona, Spain

Location

Hospital Reina Sofía

Córdoba, Spain

Location

Hospital 12 de Octubre

Madrid, Spain

Location

CHU de Santiago

Santiago de Compostela, Spain

Location

Hospital Virgen del Rocío

Seville, Spain

Location

Clatterbridge Cancer Centre NHS Foundation Trust

Liverpool, United Kingdom

Location

Barts Health NHS Trust

London, United Kingdom

Location

University College London Hospitals NHS Foundation Trust

London, United Kingdom

Location

Oxford University Hospitals NHS Foundation Trust

Oxford, United Kingdom

Location

Sheffield Teaching Hospitals NHS Foundation Trust

Sheffield, United Kingdom

Location

University Hospital Southampton NHS Foundation Trust

Southampton, United Kingdom

Location

Related Publications (3)

• Powles, T., et al., A phase II study investigating the safety and efficacy of neoadjuvant atezolizumab in muscle invasive bladder cancer (ABACUS). Journal of Clinical Oncology, 2018. 36(15_suppl): p. 4506-4506.

  RESULT

• Powles T, Kockx M, Rodriguez-Vida A, Duran I, Crabb SJ, Van Der Heijden MS, Szabados B, Pous AF, Gravis G, Herranz UA, Protheroe A, Ravaud A, Maillet D, Mendez MJ, Suarez C, Linch M, Prendergast A, van Dam PJ, Stanoeva D, Daelemans S, Mariathasan S, Tea JS, Mousa K, Banchereau R, Castellano D. Clinical efficacy and biomarker analysis of neoadjuvant atezolizumab in operable urothelial carcinoma in the ABACUS trial. Nat Med. 2019 Nov;25(11):1706-1714. doi: 10.1038/s41591-019-0628-7. Epub 2019 Nov 4.

  PMID: 31686036 RESULT

• Szabados B, Rodriguez-Vida A, Duran I, Crabb SJ, Van Der Heijden MS, Pous AF, Gravis G, Herranz UA, Protheroe A, Ravaud A, Maillet D, Mendez-Vidal MJ, Suarez C, Linch M, Prendergast A, Tyson C, Mousa K, Castellano D, Powles T. Toxicity and Surgical Complication Rates of Neoadjuvant Atezolizumab in Patients with Muscle-invasive Bladder Cancer Undergoing Radical Cystectomy: Updated Safety Results from the ABACUS Trial. Eur Urol Oncol. 2021 Jun;4(3):456-463. doi: 10.1016/j.euo.2020.11.010. Epub 2021 Feb 18.

  PMID: 33612455 DERIVED

Related Links

• Meeting Abstract: 2018 ASCO Annual Meeting

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Carcinoma, Transitional Cell

Interventions

atezolizumab

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Study Officials

• Thomas Powles, MBBS MD MRCP

  Queen Mary University of London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 18, 2016
• First Posted: January 25, 2016
• Study Start: February 1, 2016
• Primary Completion: June 11, 2020
• Study Completion: June 11, 2020
• Last Updated: March 10, 2025

Record last verified: 2025-03

Locations

GB (6); ES (9); NL (1); FR (4)