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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03528694




Registration number
NCT03528694
Ethics application status
Date submitted
28/02/2018
Date registered
18/05/2018
Date last updated
21/09/2020

Titles & IDs
Public title
Assessment of Efficacy and Safety of Durvalumab Plus BCG Compared to the Standard Therapy With BCG in Non-muscle Invasive Bladder Cancer
Scientific 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
Secondary ID [1] 0 0
D419JC00001
Universal Trial Number (UTN)
Trial acronym
POTOMAC
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-muscle-invasive Bladder Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bladder - transitional cell cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Durvalumab (MEDI4736)
Other interventions - Bacillus Calmette-Guerin (BCG)

Experimental: Durvalumab plus BCG (induction + maintenance) - Durvalumab (MEDI4736) plus Bacillus Calmette-Guerrin (BCG) combination therapy

Experimental: Durvalumab plus BCG (induction only) - Durvalumab (MEDI4736) plus Bacillus Calmette-Guerrin (BCG) combination therapy

Active Comparator: BCG treatment (Standard of care therapy) - Bacillus Calmette-Guerrin (BCG) standard of care treatment


Other interventions: Durvalumab (MEDI4736)
Investigational product

Other interventions: Bacillus Calmette-Guerin (BCG)
Standard of care

Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
The efficacy of Durvalumab + BCG (induction plus maintenance) combination therapy compared to SoC in terms of Disease free survival (DFS) in patients with NMIBC
Timepoint [1] 0 0
Up to 4 years
Secondary outcome [1] 0 0
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
Timepoint [1] 0 0
Up to 4 years
Secondary outcome [2] 0 0
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
Timepoint [2] 0 0
Up to 4 years
Secondary outcome [3] 0 0
Patient-reported treatment tolerability using specific PRO CTCAE symptoms
Timepoint [3] 0 0
Up to 4 years
Secondary outcome [4] 0 0
The serum concentration of Durvalumab plus BCG combination therapies
Timepoint [4] 0 0
Up to 4 years
Secondary outcome [5] 0 0
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.
Timepoint [5] 0 0
Up to 4 years
Secondary outcome [6] 0 0
The efficacy of Durvalumab + BCG (induction plus maintenance) therapy compare to SoC in terms of OS
Timepoint [6] 0 0
Up to 7 years
Secondary outcome [7] 0 0
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
Timepoint [7] 0 0
Up to 7 years
Secondary outcome [8] 0 0
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
Timepoint [8] 0 0
Up to 4 years
Secondary outcome [9] 0 0
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
Timepoint [9] 0 0
Up to 4 years
Secondary outcome [10] 0 0
The efficacy of Durvalumab + BCG (induction only) combination therapy compared to SoC in terms of OS
Timepoint [10] 0 0
Up to 7 years
Secondary outcome [11] 0 0
The efficacy of Durvalumab + BCG combination therapies compared to each other in terms of OS
Timepoint [11] 0 0
Up to 7 years
Secondary outcome [12] 0 0
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
Timepoint [12] 0 0
Up to 7 years
Secondary outcome [13] 0 0
The efficacy of Durvalumab + BCG combination therapies compared to each other in terms of time to muscle invasive bladder cancer and/or metastatic disease
Timepoint [13] 0 0
Up to 7 years
Secondary outcome [14] 0 0
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.
Timepoint [14] 0 0
Up to 4 years
Secondary outcome [15] 0 0
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
Timepoint [15] 0 0
Up to 4 years

Eligibility
Key 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
Minimum age
18 Years
Maximum age
130 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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)

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Auchenflower
Recruitment hospital [2] 0 0
Research Site - Box Hill
Recruitment hospital [3] 0 0
Research Site - Brisbane
Recruitment hospital [4] 0 0
Research Site - Kogarah
Recruitment hospital [5] 0 0
Research Site - Orange
Recruitment hospital [6] 0 0
Research Site - Parkville
Recruitment hospital [7] 0 0
Research Site - Westmead
Recruitment hospital [8] 0 0
Research Site - Wollongong
Recruitment postcode(s) [1] 0 0
4066 - Auchenflower
Recruitment postcode(s) [2] 0 0
3128 - Box Hill
Recruitment postcode(s) [3] 0 0
4122 - Brisbane
Recruitment postcode(s) [4] 0 0
2217 - Kogarah
Recruitment postcode(s) [5] 0 0
2800 - Orange
Recruitment postcode(s) [6] 0 0
3000 - Parkville
Recruitment postcode(s) [7] 0 0
2145 - Westmead
Recruitment postcode(s) [8] 0 0
2500 - Wollongong
Recruitment outside Australia
Country [1] 0 0
Austria
State/province [1] 0 0
Graz
Country [2] 0 0
Austria
State/province [2] 0 0
Innsbruck
Country [3] 0 0
Austria
State/province [3] 0 0
Linz
Country [4] 0 0
Austria
State/province [4] 0 0
Salzburg
Country [5] 0 0
Austria
State/province [5] 0 0
Wien
Country [6] 0 0
Belgium
State/province [6] 0 0
Brussels
Country [7] 0 0
Belgium
State/province [7] 0 0
Gent
Country [8] 0 0
Belgium
State/province [8] 0 0
Leuven
Country [9] 0 0
Belgium
State/province [9] 0 0
Roeselare
Country [10] 0 0
Canada
State/province [10] 0 0
British Columbia
Country [11] 0 0
Canada
State/province [11] 0 0
Nova Scotia
Country [12] 0 0
Canada
State/province [12] 0 0
Ontario
Country [13] 0 0
Canada
State/province [13] 0 0
Quebec
Country [14] 0 0
France
State/province [14] 0 0
Amiens
Country [15] 0 0
France
State/province [15] 0 0
Angers Cedex 01
Country [16] 0 0
France
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Bordeaux Cedex
Country [17] 0 0
France
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LYON cedex 03
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France
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Marseille
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France
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Montpellier CEDEX 5
Country [20] 0 0
France
State/province [20] 0 0
Strasbourg Cedex
Country [21] 0 0
France
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Suresnes
Country [22] 0 0
Germany
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Berlin
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Germany
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Duisburg
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Germany
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Hannover
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Germany
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Heidelberg
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Germany
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Heinsberg
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Germany
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Köln
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Germany
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Marburg
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Germany
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Mettmann
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Germany
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Mühlheim An Der Ruhr
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Germany
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München
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Münster
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Germany
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Nürtingen
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Germany
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Wesel
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Germany
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Würselen
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Germany
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Zirndorf
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Japan
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Bunkyo-ku
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Fukuoka
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Osakasayama-shi
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Shinjuku-ku
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Obninsk
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Omsk
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Vologda
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Yaroslavl
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Slovakia
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Banka
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Bratislava
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Martin
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Badajoz
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Barcelona
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Elche(Alicante)
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Malaga
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Pamplona
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Valencia
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Birmingham
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Sheffield
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Southampton
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United Kingdom
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Taunton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
AstraZeneca
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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.
Trial website
https://clinicaltrials.gov/show/NCT03528694
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
AstraZeneca Clinical Study Information Center
Address 0 0
Country 0 0
Phone 0 0
1-877-240-9479
Fax 0 0
Email 0 0
information.center@astrazeneca.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03528694