Assessment of Efficacy and Safety of Durvalumab Plus BCG Compared to the Standard Therapy With BCG in Non-muscle Invasive Bladder Cancer

Non-muscle-invasive Bladder Cancer Clinical Trial

— POTOMAC  

Official title:

A Phase III Randomized, Open-Label, Multi-Center, Global Study of Durvalumab and Bacillus Calmette-Guerin (BCG) Administered as Combination Therapy Versus BCG Alone in High-Risk, BCG Naïve Non-Muscle Invasive Bladder Cancer Patients

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03528694
• Other study ID #: D419JC00001
• Secondary ID: 2017-002979-26
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: May 14, 2018
• Est. completion date: September 30, 2025

Study information

• Verified date: February 2024
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a randomized, open-label, multi-center, global, phase III study to determine the efficacy and safety of Durvalumab + BCG combination therapy in the treatment of patients with non-muscle-invasive bladder cancer

Description:

Patients will be randomized in a 1:1:1 ratio to receive treatment with Durvalumab + BCG combination therapies, or Standard of Care (SoC) therapy.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1018
• Est. completion date: September 30, 2025
• Est. primary completion date: October 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 130 Years

Eligibility

Inclusion Criteria: For inclusion in the study, patients should fulfill the following

criteria:

• Aged at least 18 years
• BCG-naïve (patients who have not received prior intravesical BCG or who previously received but stopped BCG more than 3 years before study entry are eligible)
• Local histological confirmation (based on pathology report) of high-risk transitional cell carcinoma of the urothelium of the urinary bladder confined to the mucosa or submucosa. A high risk tumor is defined as one of the following
• T1 tumor
• High grade/ G3 tumor
• CIS
• Multiple and recurrent and large (with diameter of largest tumor =3 cm) tumors (all conditions must be met in this point)
• Complete resection of all Ta/T1 papillary disease prior to randomization, with the TURBT removing high-risk NMIBC performed not more than 4 months before randomization in the study. Patients with residual CIS after TURBT are eligible
• No prior radiotherapy for bladder cancer
• No prior exposure to immune-mediated therapy of cancer including, but not limited to, other anti CTLA-4, anti-PD-1, anti-PD-L1, and anti-programmed cell death ligand 2 antibodies. Patients who have been treated with anticancer vaccines will be excluded Exclusion Criteria: Patients should not enter the study if any of the following exclusion criteria are

fulfilled:

• Evidence of muscle-invasive, locally advanced, metastatic, and/or extra vesical bladder cancer (ie, T2, T3, T4, and / or stage IV)
• Concurrent extravesical (ie, urethra, ureter, or renal pelvis), non-muscle-invasive transitional cell carcinoma of the urothelium
• Previous investigational product (IP) assignment in the present study
• Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for noncancer related conditions (eg, hormone replacement therapy) is acceptable. Chemotherapy for previous instances of NMIBC is acceptable.
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this

criterion:

• Patients with vitiligo or alopecia
• Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
• Any chronic skin condition that does not require systemic therapy
• Patients without active disease in the last 5 years may be included but only after consultation with the Study Physician
• Patients with celiac disease controlled by diet alone
• History of another primary malignancy except for
• Malignancy treated with curative intent and with no known active disease = 2 years before the first dose of IP and of low potential risk for recurrence during the study period
• Adequately treated nonmelanoma skin cancer or lentigo maligna withoutevidence of disease
• Adequately treated CIS without evidence of disease
• Prostate cancer (tumor/node/metastasis stage) of stage = T2cN0M0 without biochemical recurrence or progression that in the opinion of the Investigator does not require active intervention
• Current or prior use of immunosuppressive medication within 14 days before the first

dose of durvalumab. The following are exceptions to this criterion:

• Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra articular injection)
• Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
• Steroids as premedication for hypersensitivity reactions (eg, computed tomography [CT] scan premedication)

Related Conditions & MeSH terms

• Non-muscle-invasive Bladder Cancer
• Urinary Bladder Neoplasms

Intervention

Biological:
• Durvalumab (MEDI4736)
Investigational product
• Bacillus Calmette-Guerin (BCG)
Standard of care

Locations

Country	Name	City	State
Australia	Research Site	Auchenflower
Australia	Research Site	Box Hill
Australia	Research Site	Brisbane
Australia	Research Site	Kogarah
Australia	Research Site	Orange
Australia	Research Site	Parkville
Australia	Research Site	Westmead
Australia	Research Site	Wollongong
Austria	Research Site	Graz
Austria	Research Site	Innsbruck
Austria	Research Site	Linz
Austria	Research Site	Salzburg
Austria	Research Site	Wien
Belgium	Research Site	Brussels
Belgium	Research Site	Gent
Belgium	Research Site	Leuven
Belgium	Research Site	Roeselare
Canada	Research Site	Chicoutimi	Quebec
Canada	Research Site	Kingston	Ontario
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Quebec
Canada	Research Site	Toronto	Ontario
France	Research Site	Amiens
France	Research Site	Angers Cedex 01
France	Research Site	Bordeaux Cedex
France	Research Site	LYON cedex 03
France	Research Site	Marseille
France	Research Site	Montpellier CEDEX 5
France	Research Site	Strasbourg Cedex
France	Research Site	Suresnes Cedex
Germany	Research Site	Berlin
Germany	Research Site	Duisburg
Germany	Research Site	Hannover
Germany	Research Site	Heidelberg
Germany	Research Site	Köln
Germany	Research Site	Marburg
Germany	Research Site	Mettmann
Germany	Research Site	Mühlheim An Der Ruhr
Germany	Research Site	München
Germany	Research Site	Münster
Germany	Research Site	Nürtingen
Germany	Research Site	Wesel
Germany	Research Site	Würselen
Germany	Research Site	Zirndorf
Japan	Research Site	Bunkyo-ku
Japan	Research Site	Fukuoka
Japan	Research Site	Hirosaki-shi
Japan	Research Site	Kanazawa-shi
Japan	Research Site	Kita-gun
Japan	Research Site	Koshigaya-shi
Japan	Research Site	Koto-ku
Japan	Research Site	Matsuyama-shi
Japan	Research Site	Miyazaki-city
Japan	Research Site	Nagasaki-shi
Japan	Research Site	Nagoya-shi
Japan	Research Site	Okayama-shi
Japan	Research Site	Osaka-shi
Japan	Research Site	Osaka-shi
Japan	Research Site	Osakasayama-shi
Japan	Research Site	Sapporo-shi
Japan	Research Site	Shinjuku-ku
Japan	Research Site	Toyama-shi
Japan	Research Site	Tsukuba-shi
Japan	Research Site	Yokohama-shi
Netherlands	Research Site	Amsterdam
Netherlands	Research Site	Breda
Netherlands	Research Site	Utrecht
Poland	Research Site	Bialystok
Poland	Research Site	Gdansk
Poland	Research Site	Grudziadz
Poland	Research Site	Koszalin
Poland	Research Site	Piotrków Trybunalski
Poland	Research Site	Poznan
Poland	Research Site	Warszawa
Poland	Research Site	Warszawa
Poland	Research Site	Wroclaw
Poland	Research Site	Wroclaw
Russian Federation	Research Site	Ivanovo
Russian Federation	Research Site	Krasnoyarsk
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Nizhniy Novgorod
Russian Federation	Research Site	Obninsk
Russian Federation	Research Site	Omsk
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Saint-Petersburg
Russian Federation	Research Site	St Petersburg
Russian Federation	Research Site	St. Petersburg
Russian Federation	Research Site	St. Petersburg
Russian Federation	Research Site	St.Petersburg
Russian Federation	Research Site	Vologda
Russian Federation	Research Site	Yaroslavl
Spain	Research Site	Badajoz
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Elche(Alicante)
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Malaga
Spain	Research Site	Oviedo
Spain	Research Site	Pamplona
Spain	Research Site	Pozuelo de Alarcon
Spain	Research Site	Sevilla
Spain	Research Site	Sevilla
Spain	Research Site	Valencia
Spain	Research Site	Valencia
United Kingdom	Research Site	Birmingham
United Kingdom	Research Site	Glasgow
United Kingdom	Research Site	Guildford
United Kingdom	Research Site	London
United Kingdom	Research Site	London
United Kingdom	Research Site	London
United Kingdom	Research Site	Sheffield
United Kingdom	Research Site	Southampton
United Kingdom	Research Site	Taunton

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

Australia,  Austria,  Belgium,  Canada,  France,  Germany,  Japan,  Netherlands,  Poland,  Russian Federation,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of treatment-related adverse events as assessed by CTCAE v4.0 in patients receiving Durvalumab + BCG combination therapies compared to SoC	The safety and tolerability profile of Durvalumab + BCG combination therapies compared to SoC using vital signs, laboratory data, electrocardiograms (ECGs), and adverse event data.	Up to 4 years
Primary	The efficacy of Durvalumab + BCG (induction plus maintenance) combination therapy compared to SoC in terms of Disease free survival (DFS) in patients with NMIBC		Up to 4 years
Secondary	The efficacy of Durvalumab + BCG (induction plus maintenance) therapy compare to SoC in terms of DFS after 24 months of last subject's last dose of IP		Up to 4 years
Secondary	Disease-related symptoms and HRQoL in patients with NMIBC treated with Durvalumab + BCG combination therapies compared to SoC and compared to each other using the EORTC QLQ-C30 questionnaire	EORTC QLQ-C30 measures cancer patients' functioning (HRQoL) and symptoms for all cancer types and consists of functional, symptom and a global measure of health status scales	Up to 4 years
Secondary	Patient-reported treatment tolerability using specific PRO CTCAE symptoms		Up to 4 years
Secondary	The serum concentration of Durvalumab plus BCG combination therapies		Up to 4 years
Secondary	The immunogenicity of Durvalumab when used in combination with BCG treatment assessed by descriptive summary of presence of ADAs	Serum will be tested for the presence of anti-drug antibodies.	Up to 4 years
Secondary	The efficacy of Durvalumab + BCG (induction plus maintenance) therapy compare to SoC in terms of OS		Up to 7 years
Secondary	The efficacy of Durvalumab + BCG (induction plus maintenance) combination therapy compared to SoC in terms of time to muscle invasive bladder cancer and/or metastatic disease		Up to 7 years
Secondary	The efficacy of Durvalumab + BCG (induction only) combination therapy compared to SoC in terms of DFS after 24 months of last subject's last dose of IP		Up to 4 years
Secondary	The efficacy of Durvalumab + BCG combination therapies compared to each other in terms of DFS after 24 months of last subject's last dose of IP		Up to 4 years
Secondary	The efficacy of Durvalumab + BCG (induction only) combination therapy compared to SoC in terms of OS		Up to 7 years
Secondary	The efficacy of Durvalumab + BCG combination therapies compared to each other in terms of OS		Up to 7 years
Secondary	The efficacy of Durvalumab + BCG (induction only) combination therapy compared to SoC in terms of time to muscle invasive bladder cancer and/or metastatic disease		Up to 7 years
Secondary	The efficacy of Durvalumab + BCG combination therapies compared to each other in terms of time to muscle invasive bladder cancer and/or metastatic disease		Up to 7 years
Secondary	Disease-related symptoms and HRQoL in patients with NMIBC treated with Durvalumab + BCG combination therapies compared to SoC and compared to each other using the the EORTC QLQ NMIBC24 questionnaire	EORTC QLQ-NMIBC24 assesses disease-specific symptoms of patients with intermediate to high-risk NMIBC.	Up to 4 years
Secondary	The efficacy of durvalumab + BCG combination therapy compared to SoC in terms of CRR for patients with CIS prior to study entry or at baseline cystoscopy	CRR at 6 months in patients with CIS prior to the study entry or at baseline cystoscopy	Up to 4 years