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NCT Number: NCT03682068

Study of Durvalumab Given With Chemotherapy, Durvalumab in Combination With Tremelimumab Given With Chemotherapy, or Chemotherapy in Patients With Unresectable Urothelial Cancer

This is a randomized, open-label, controlled, multi-center, global Phase III study to determine the efficacy and safety of combining durvalumab ± tremelimumab with standard of care (SoC) chemotherapy (cisplatin + gemcitabine or carboplatin + gemcitabine doublet) followed by durvalumab monotherapy versus SoC alone as first-line chemotherapy in patients with histologically or cytologically documented, unresectable, locally advanced or metastatic transitional cell carcinoma of the urothelium (including renal pelvis, ureters, urinary bladder, and urethra).

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This study is active but is not currently recruiting participants.

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Key information

Conditions

Unresectable Locally Advanced Urothelial Cancer Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Male Urogenital Diseases Metastatic Urothelial Cancer Neoplasms Neoplasms by Site 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, Ciudad de Buenos Aires, Argentina

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

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

Key Inclusion Criteria:

  • Patients with histologically or cytologically documented, unresectable, locally advanced or metastatic transitional cell carcinoma (transitional cell and mixed transitional/non-transitional cell histologies) of the urothelium (including renal pelvis, ureters, urinary bladder, and urethra)
  • Patients who have not been previously treated with first-line chemotherapy. Patients who have received prior definitive chemoradiation, adjuvant or neoadjuvant treatment for locally advanced disease are eligible provided that progression to locally advanced or metastatic disease has occurred >12 months from the last therapy [for chemoradiation and adjuvant treatment] or >12 months from the last surgery [for neoadjuvant treatment].
  • At least 1 lesion, not previously irradiated, that qualifies as a RECIST 1.1 target lesion at baseline.
  • World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 at enrolment
  • Adequate organ and marrow function as defined in the protocol
  • Life expectancy ≥12 weeks in the opinion of the investigator
  • Evidence of post-menopausal status, or negative urinary or serum pregnancy test for female pre-menopausal patients.

Key Exclusion Criteria:

  • Prior exposure to immune-mediated therapy (with exclusion of Bacillus Calmette Guerin), including but not limited to, other anti-CTLA-4, anti-PD-1, anti-PD L1, or anti-PD-L2 antibodies, except therapeutic anticancer vaccines, which are permitted. Prior local intervesical chemotherapy or immunotherapy is allowed if completed at least 28 days prior to the initiation of study treatment.
  • No severe concomitant condition that requires immunosuppression medication
  • Untreated central nervous system (CNS) metastases and/or carcinomatous meningitis
  • Patients who may be eligible for or are being considered for radical resection during the course of the study.
  • Any medical contraindications to platinum (cisplatin or carboplatin) based doublet chemotherapy and/or known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients

Treatment and study plan

Durvalumab

Drug

Durvalumab IV (intravenous infusion)

Other names: MEDI4736

Tremelimumab

Drug

Tremelimumab IV (intravenous infusion)

Cisplatin + Gemcitabine

Drug

Cisplatin IV (intravenous)+ Gemcitabine IV(intravenous), as standard of care.

Carboplatin + Gemcitabine

Drug

Carboplatin IV (intravenous)+ Gemcitabine IV(intravenous), as standard of care.

Primary outcomes

  1. Overall Survival (OS)

    Time frame: approximately 5 years

    OS is defined as the time from the date of randomization until death due to any cause

Secondary outcomes

  1. Overall Survival (OS)

    Time frame: approximately 5 years

    Additional analysis beyond the primary endpoint

  2. Overall Survival at 24 months (OS24)

    Time frame: 24 months

    The OS24 will be defined as the Kaplan-Meier estimate of OS at 24 months

  3. Progression Free Survival (PFS)

    Time frame: approximately 5 years

    PFS (per RECIST 1.1) will be defined as the time from the date of randomization until the date of first objective disease progression or death

  4. Alive and Progression Free Survival at 12 months (APF12)

    Time frame: 12 months

    The APF12 will be defined as the Kaplan-Meier estimate of PFS (per RECIST 1.1) at 12 months

  5. Objective Response Rate (ORR)

    Time frame: approximately 5 years

    ORR (per RECIST 1.1) is defined as the number (%) of patients with at least 1 visit response of complete response or partial response and will be based on a subset of all randomized patients

  6. Duration of Response (DoR)

    Time frame: approximately 5 years

    DoR (per RECIST 1.1) will be defined as the time from the date of first documented response until the first date of documented progression or death in the absence of disease progression

  7. Disease Control Rate (DCR)

    Time frame: approximately 5 years

    DCR is defined as the proportion of subjects with the best overall response of complete response, partial response or stable disease per RECIST 1.1

  8. Time from randomization to second (PFS2)

    Time frame: approximately 5 years

    PFS2 will be defined as the time from the date of randomization to the earliest of the progression events subsequent to that used for the PFS endpoint or death

  9. To assess disease-related symptoms, physical functioning, and other Health-related quality of life

    Time frame: approximately 5 years

    Collection of patient reported outcome questionnaires

Other outcomes

  1. To assess safety using a summary of adverse events.

    Time frame: approximately 5 years

    Adverse Events (both in terms of MedDRA preferred terms and CTCAE grade) will be listed individually by patient. The number of patients experiencing each Adverse Event will be summarized by treatment arm and CTCAE grade

  2. To assess pharmacokinetics of Durvalumab and Tremelimumab

    Time frame: approximately 5 years

    Serum concentrations of Durvalumab and Tremelimumab

  3. To assess immunogenicity of Durvalumab and Tremelimumab

    Time frame: approximately 5 years

    Presence of anti-drug antibodies for Durvalumab and Tremelimumab

Sponsors and collaborators

Lead sponsor

AstraZeneca

Industry

Registry information

Official study title

A Phase III, Randomized, Open-Label, Controlled, Multi-Center, Global Study of First-Line Durvalumab in Combination With Standard of Care Chemotherapy and Durvalumab in Combination With Tremelimumab and Standard of Care Chemotherapy Versus Standard of Care Chemotherapy Alone in Patients With Unresectable Locally Advanced or Metastatic Urothelial Cancer.

Acronym: NILE

Important dates

Study start
2018
Primary completion
2026
Study completion
2027
First posted
Sep 24, 2018
Registry last updated
May 28, 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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