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NCT Number: NCT03528694

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

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

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This study is active but is not currently recruiting participants.

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Key information

Conditions

Non-muscle-invasive Bladder Cancer Carcinoma Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Male Urogenital Diseases Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Glandular and Epithelial Non-Muscle Invasive Bladder Neoplasms Urinary Bladder Diseases Urinary Bladder Neoplasms Urogenital Diseases Urogenital Neoplasms Urologic Diseases Urologic Neoplasms

Age range

18 year–130 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Research Site, Auchenflower, Australia

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About this study

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

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

Durvalumab (MEDI4736)

Biological

Investigational product

Bacillus Calmette-Guerin (BCG)

Biological

Standard of care

Primary outcomes

  1. 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

    Disease-free survival using Investigator disease assessments.

Secondary outcomes

  1. To assess the efficacy of durvalumab + BCG (induction and maintenance) combination therapy compared to BCG (induction and maintenance) alone in terms of DFS 24 months

    Time frame: Up to 4 years

    Proportion of patients alive and disease free at 24 months using Investigator disease assessments. DFS24 is defined as the proportion of patients alive and disease-free at 24 months after randomization, per Investigator disease assessment.

  2. To assess the efficacy of durvalumab + BCG (induction and maintenance) combination therapy compared to BCG (induction and maintenance) alone in terms of OS5

    Time frame: Up to 7 years

    Overall survival at 5 years. Overall survival (OS) is defined as the time from the date of randomization until death due to any cause regardless of whether the patient withdraws from randomized therapy or receives another anti-cancer therapy (i.e. date of death or censoring - date of randomization +1). Any patient not known to have died at the time of analysis will be censored based on the last recorded date on which the patient was known to be alive

  3. To assess the efficacy of durvalumab + BCG (induction and maintenance) combination therapy compared to BCG (induction and maintenance) alone in terms of any disease-free survival

    Time frame: Up to 7 years

    Any disease-free survival using Investigator disease assessments. Any disease-free survival (aDFS) is defined similarly as DFS, except that aDFS includes recurrence of low/medium risk NMIBC. This will be based on Investigator disease assessments.

  4. To assess the efficacy of durvalumab + BCG (induction and maintenance) combination therapy compared to BCG (induction and maintenance) alone in terms of Time to MIBC and/or Metastatic Disease

    Time frame: Up to 4 years

    Time to MIBC and/or metastatic disease using Investigator disease assessments. Time to MIBC and/or metastatic disease is defined as the time from the date of randomization until the date of first documented MIBC and/or metastatic disease as assessed by Investigator. Time to MIBC and/or metastatic disease does not include deaths. If patients died without MIBC and/or metastatic disease, they will be censored at the time of death. All other censoring rules per DFS analysis will be applied including censoring patients with an event after 2 missed visits and patients with no evaluable disease assessments or no baseline data.

  5. To assess the efficacy of durvalumab + BCG (induction and maintenance) combination therapy compared to BCG (induction and maintenance) alone with respect to time to cystectomy

    Time frame: Up to 4 years

    Time to cystectomy using Investigator disease assessments. Time to cystectomy is defined as the time from the date of randomization until the date of cystectomy as reported by Investigator. Patients who died prior to cystectomy will be censored at the time of death. Patients who have not had a cystectomy at the time of analysis will be censored at the last recorded date on which the patient was known to be alive. No other censoring rules per the DFS analysis will be applied.

  6. To assess the efficacy of durvalumab + BCG (induction and maintenance) combination therapy compared to BCG (induction and maintenance) alone in terms of time to development of upper tract urothelial carcinoma

    Time frame: Up to 7 years

    Time to development of upper tract urothelial carcinoma using Investigator disease assessments. Time to development of upper tract urothelial carcinoma (TTUTUC) is defined as the time from the date of randomization until the date of development of upper tract urothelial carcinoma as assessed by Investigator using CT urography or ureteroscopy (less common). TTUTUC does not include deaths. Patients who died without upper tract urothelial carcinoma will be censored at the time of death. Other censoring rules per DFS analysis will be applied, including censoring patients with no baseline data but excluding censoring patients with an event after 2 missed visits as evaluation of the upper urinary tract is not part of regular disease assessment and is performed as clinically indicated.

  7. To assess the efficacy of durvalumab + BCG (induction only) combination therapy compared to BCG (induction and maintenance) alone in terms of Disease-free survival

    Time frame: Up to 7 years

    Any disease-free survival (aDFS) is defined similarly as DFS, except that aDFS includes recurrence of low/medium risk NMIBC. This will be based on Investigator disease assessments.

  8. To assess the efficacy of durvalumab + BCG (induction only) combination therapy compared to BCG (induction and maintenance) alone in terms of patients alive and disease free at 24 months

    Time frame: Up to 24 months

    Proportion of patients alive and disease free at 24 months using Investigator disease assessments. DFS24 is defined as the proportion of patients alive and disease-free at 24 months after randomization, per Investigator disease assessment

  9. To assess the efficacy of durvalumab + BCG (induction only) combination therapy compared to BCG (induction and maintenance) alone in terms of OS5

    Time frame: up to 5 years

    Overall survival at 5 years. Overall survival (OS) is defined as the time from the date of randomization until death due to any cause regardless of whether the patient withdraws from randomized therapy or receives another anti-cancer therapy (i.e. date of death or censoring - date of randomization +1).

  10. To assess the efficacy of durvalumab + BCG (induction only) combination therapy compared to BCG (induction and maintenance) alone in terms of any disease-free survival

    Time frame: Up to 7 years

    Any disease-free survival using Investigator disease assessments. Any disease-free survival (aDFS) is defined similarly as DFS, except that aDFS includes recurrence of low/medium risk NMIBC. This will be based on Investigator disease assessments.

  11. To assess the efficacy of durvalumab + BCG (induction only) combination therapy compared to BCG (induction and maintenance) alone in terms of Time to MIBC and/or metastatic disease

    Time frame: Up to 7 years

    Time to MIBC and/or metastatic disease using Investigator disease assessments. Time to MIBC and/or metastatic disease is defined as the time from the date of randomization until the date of first documented MIBC and/or metastatic disease as assessed by Investigator. Time to MIBC and/or metastatic disease does not include deaths. If patients died without MIBC and/or metastatic disease, they will be censored at the time of death. All other censoring rules per DFS analysis will be applied including censoring patients with an event after 2 missed visits and patients with no evaluable disease assessments or no baseline data.

  12. To assess the efficacy of durvalumab + BCG (induction only) combination therapy compared to BCG (induction and maintenance) alone in terms of time to cystectomy

    Time frame: Up to 7 years

    Time to cystectomy using Investigator disease assessments. Time to cystectomy is defined as the time from the date of randomization until the date of cystectomy as reported by Investigator. Patients who died prior to cystectomy will be censored at the time of death. Patients who have not had a cystectomy at the time of analysis will be censored at the last recorded date on which the patient was known to be alive. No other censoring rules per the DFS analysis will be applied.

  13. To assess the efficacy of durvalumab + BCG (induction only) combination therapy compared to BCG (induction and maintenance) alone time to development of upper tract urothelial carcinoma

    Time frame: Up to 7 years

    Time to development of upper tract urothelial carcinoma using Investigator disease assessments. Time to development of upper tract urothelial carcinoma (TTUTUC) is defined as the time from the date of randomization until the date of development of upper tract urothelial carcinoma as assessed by Investigator using CT urography or ureteroscopy (less common). TTUTUC does not include deaths. Patients who died without upper tract urothelial carcinoma will be censored at the time of death. Other censoring rules per DFS analysis will be applied, including censoring patients with no baseline data but excluding censoring patients with an event after 2 missed visits as evaluation of the upper urinary tract is not part of regular disease assessment and is performed as clinically indicated.

  14. To assess the efficacy of durvalumab + BCG (induction and maintenance) combination therapy compared to durvalumab + BCG (induction only) in terms of Disease-free survival

    Time frame: Up to 4 years

    Disease-free survival using Investigator disease assessments.Any disease-free survival (aDFS) is defined similarly as DFS, except that aDFS includes recurrence of low/medium risk NMIBC. This will be based on Investigator disease assessments.

  15. To assess the efficacy of durvalumab + BCG (induction and maintenance) combination therapy compared to durvalumab + BCG (induction only) in terms of Proportion of patients alive and disease free at 24 months

    Time frame: Up to 24 months

    Proportion of patients alive and disease free at 24 months using Investigator disease assessments. DFS24 is defined as the proportion of patients alive and disease-free at 24 months after randomization, per Investigator disease assessment.

  16. To assess the efficacy of durvalumab + BCG (induction and maintenance) combination therapy compared to durvalumab + BCG (induction only) in terms of Overall survival at 5 years

    Time frame: Up to 7 years

    Overall survival (OS) is defined as the time from the date of randomization until death due to any cause regardless of whether the patient withdraws from randomized therapy or receives another anti-cancer therapy (i.e. date of death or censoring - date of randomization +1). The proportion of patients alive at 5 years (OS5)

  17. To assess the efficacy of durvalumab + BCG (induction and maintenance) combination therapy compared to durvalumab + BCG (induction only) in terms of any disease-free survival

    Time frame: up to 5 years

    Any disease-free survival using Investigator disease assessments. Any disease-free survival (aDFS) is defined similarly as DFS, except that aDFS includes recurrence of low/medium risk NMIBC. This will be based on Investigator disease assessments.

  18. To assess the efficacy of durvalumab + BCG (induction and maintenance) combination therapy compared to durvalumab + BCG (induction only) in terms of time to MIBC and/or metastatic disease

    Time frame: up to 5 yeas

    Time to MIBC and/or metastatic disease using Investigator disease assessments. Time to MIBC and/or metastatic disease is defined as the time from the date of randomization until the date of first documented MIBC and/or metastatic disease as assessed by Investigator. Time to MIBC and/or metastatic disease does not include deaths. If patients died without MIBC and/or metastatic disease, they will be censored at the time of death. All other censoring rules per DFS analysis will be applied including censoring patients with an event after 2 missed visits and patients with no evaluable disease assessments or no baseline data.

  19. To assess the efficacy of durvalumab + BCG (induction and maintenance) combination therapy compared to durvalumab + BCG (induction only) in terms of time to cystectomy

    Time frame: up to 5 years

    Time to cystectomy using Investigator disease assessments. Time to cystectomy is defined as the time from the date of randomization until the date of cystectomy as reported by Investigator. Patients who died prior to cystectomy will be censored at the time of death.

    Patients who have not had a cystectomy at the time of analysis will be censored at the last recorded date on which the patient was known to be alive. No other censoring rules per the DFS analysis will be applied.

  20. To assess the efficacy of durvalumab + BCG (induction and maintenance) combination therapy compared to durvalumab + BCG (induction only) in terms of Time to development of upper tract urothelial carcinoma

    Time frame: up to 5 years

    Time to development of upper tract urothelial carcinoma using Investigator disease assessments. Time to development of upper tract urothelial carcinoma (TTUTUC) is defined as the time from the date of randomization until the date of development of upper tract urothelial carcinoma as assessed by Investigator using CT urography or ureteroscopy (less common). TTUTUC does not include deaths. Patients who died without upper tract urothelial carcinoma will be censored at the time of death. Other censoring rules per DFS analysis will be applied, including censoring patients with no baseline data but excluding censoring patients with an event after 2 missed visits as evaluation of the upper urinary tract is not part of regular disease assessment and is performed as clinically indicated.

  21. Complete response rate (CRR) at 6 months using Investigator disease assessments

    Time frame: up to 6 months

    To assess the efficacy of durvalumab + BCG combination therapy compared to BCG (induction and maintenance) for patients with CIS prior to study entry or at baseline cystoscopy.

  22. EORTC QLQ-C30 and EORTC QLQ-NMIBC24

    Time frame: up to 5 years

    To assess disease-related symptoms and HRQoL in patients with NMIBC treated with durvalumab + BCG (induction and maintenance) combination therapy and durvalumab + BCG (induction only) combination therapy compared to BCG (induction and maintenance) alone and compared to each other using the EORTC QLQ-C30 questionnaire and the EORTC QLQ-NMIBC24 questionnaire

  23. PRO version of the CTCAE with approximately 19 items (PRO-CTCAE) symptoms in countries where language is available

    Time frame: up to 5 years

    To assess patient-reported treatment tolerability directly using specific PRO-CTCAE symptoms

  24. PK serum concentration of durvalumab

    Time frame: up to 5 years

    To assess the PK of durvalumab when used in combination with BCG treatment

  25. Presence of ADAs for durvalumab

    Time frame: up to 5 years

    To investigate the immunogenicity of durvalumab when used in combination with BCG treatment

Sponsors and collaborators

Lead sponsor

AstraZeneca

Industry

Registry information

Official study 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

Acronym: POTOMAC

Important dates

Study start
2018
Primary completion
2025
Study completion
2028
First posted
May 18, 2018
Registry last updated
Jul 7, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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