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

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ClinicalTrials.gov Identifier: NCT03528694
Recruitment Status : Recruiting
First Posted : May 18, 2018
Last Update Posted : August 26, 2019
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Tracking Information
First Submitted Date  ICMJE February 28, 2018
First Posted Date  ICMJE May 18, 2018
Last Update Posted Date August 26, 2019
Actual Study Start Date  ICMJE May 14, 2018
Estimated Primary Completion Date November 24, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 10, 2018)
The efficacy of Durvalumab + BCG (induction plus maintenance) combination therapy compared to SoC in terms of Disease free survival (DFS) in patients with NMIBC [ Time Frame: Up to 4 years ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03528694 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 10, 2018)
  • 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 [ Time Frame: Up to 4 years ]
  • 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 [ Time Frame: Up to 4 years ]
    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
  • Patient-reported treatment tolerability using specific PRO CTCAE symptoms [ Time Frame: Up to 4 years ]
  • The serum concentration of Durvalumab plus BCG combination therapies [ Time Frame: Up to 4 years ]
  • The immunogenicity of Durvalumab when used in combination with BCG treatment assessed by descriptive summary of presence of ADAs [ Time Frame: Up to 4 years ]
    Serum will be tested for the presence of anti-drug antibodies.
  • The efficacy of Durvalumab + BCG (induction plus maintenance) therapy compare to SoC in terms of OS [ Time Frame: Up to 7 years ]
  • 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 [ Time Frame: Up to 7 years ]
  • 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 [ Time Frame: Up to 4 years ]
  • 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 [ Time Frame: Up to 4 years ]
  • The efficacy of Durvalumab + BCG (induction only) combination therapy compared to SoC in terms of OS [ Time Frame: Up to 7 years ]
  • The efficacy of Durvalumab + BCG combination therapies compared to each other in terms of OS [ Time Frame: Up to 7 years ]
  • 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 [ Time Frame: Up to 7 years ]
  • The efficacy of Durvalumab + BCG combination therapies compared to each other in terms of time to muscle invasive bladder cancer and/or metastatic disease [ Time Frame: Up to 7 years ]
  • 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 [ Time Frame: Up to 4 years ]
    EORTC QLQ-NMIBC24 assesses disease-specific symptoms of patients with intermediate to high-risk NMIBC.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: May 10, 2018)
Number of treatment-related adverse events as assessed by CTCAE v4.0 in patients receiving Durvalumab + BCG combination therapies compared to SoC [ Time Frame: Up to 4 years ]
The safety and tolerability profile of Durvalumab + BCG combination therapies compared to SoC using vital signs, laboratory data, electrocardiograms (ECGs), and adverse event data.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Assessment of Efficacy and Safety of Durvalumab Plus BCG Compared to the Standard Therapy With BCG in Non-muscle Invasive Bladder Cancer
Official Title  ICMJE 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
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.
Detailed 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Non-muscle-invasive Bladder Cancer
Intervention  ICMJE
  • Biological: Durvalumab (MEDI4736)
    Investigational product
  • Biological: Bacillus Calmette-Guerin (BCG)
    Standard of care
Study Arms  ICMJE
  • Experimental: Durvalumab plus BCG (induction + maintenance)
    Durvalumab (MEDI4736) plus Bacillus Calmette-Guerrin (BCG) combination therapy
    Interventions:
    • Biological: Durvalumab (MEDI4736)
    • Biological: Bacillus Calmette-Guerin (BCG)
  • Experimental: Durvalumab plus BCG (induction only)
    Durvalumab (MEDI4736) plus Bacillus Calmette-Guerrin (BCG) combination therapy
    Interventions:
    • Biological: Durvalumab (MEDI4736)
    • Biological: Bacillus Calmette-Guerin (BCG)
  • Active Comparator: BCG treatment (Standard of care therapy)
    Bacillus Calmette-Guerrin (BCG) standard of care treatment
    Intervention: Biological: Bacillus Calmette-Guerin (BCG)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 10, 2018)
975
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 25, 2024
Estimated Primary Completion Date November 24, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 130 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com
Listed Location Countries  ICMJE Australia,   Austria,   Belgium,   Canada,   France,   Germany,   Japan,   Netherlands,   Poland,   Russian Federation,   Slovakia,   Spain,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03528694
Other Study ID Numbers  ICMJE D419JC00001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE Not Provided
Responsible Party AstraZeneca
Study Sponsor  ICMJE AstraZeneca
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account AstraZeneca
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP