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

Sponsor
AstraZeneca (Industry)
Overall Status
Recruiting
CT.gov ID
NCT03682068
Collaborator
(none)
1,292
Enrollment
238
Locations
3
Arms
85.1
Anticipated Duration (Months)
5.4
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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).

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Anticipated Enrollment :
1292 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official 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.
Actual Study Start Date :
Sep 27, 2018
Anticipated Primary Completion Date :
Jun 30, 2023
Anticipated Study Completion Date :
Oct 30, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: Durvalumab in Combination with SoC Chemotherapy

Durvalumab every 3 weeks in concurrence with chemotherapy, followed by durvalumab monotherapy every 4 weeks. All patients will receive one of the following standard of care chemotherapy regimens every 3 weeks for 6 cycles: cisplatin+ gemcitabine If the patient is cisplatin-ineligible, carboplatin + gemcitabine

Drug: Durvalumab
Durvalumab IV (intravenous infusion)
Other Names:
  • MEDI4736

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

    Drug: Carboplatin + Gemcitabine
    Carboplatin IV (intravenous)+ Gemcitabine IV(intravenous), as standard of care.
    Experimental: Durvalumab in Combination with Tremelimumab+SoC Chemotherapy

    Durvalumab and Tremelimumab every 3 weeks in concurrence with chemotherapy, followed by durvalumab monotherapy every 4 weeks Tremelimumab will be provided for 4 cycles. All patients will receive one of the following standard of care chemotherapy regimens every 3 weeks for 6 cycles: cisplatin+ gemcitabine If the patient is cisplatin-ineligible, carboplatin + gemcitabine

    Drug: Durvalumab
    Durvalumab IV (intravenous infusion)
    Other Names:
  • MEDI4736

    • Drug: Tremelimumab
    Tremelimumab IV (intravenous infusion)

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

    Drug: Carboplatin + Gemcitabine
    Carboplatin IV (intravenous)+ Gemcitabine IV(intravenous), as standard of care.
    Active Comparator: SoC Chemotherapy

    Patients will receive one of the following standard of care chemotherapy regimens every 3 weeks for 6 cycles: cisplatin+ gemcitabine If the patient is cisplatin-ineligible, carboplatin + gemcitabine

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

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

    Outcome Measures

    Primary Outcome Measures

    1. Overall Survival (OS) [approximately 5 years]

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

    Secondary Outcome Measures

    1. Overall Survival (OS) [approximately 5 years]

      Additional analysis beyond the primary endpoint

    2. Overall Survival at 24 months (OS24) [24 months]

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

    3. Progression Free Survival (PFS) [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) [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) [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) [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) [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) [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 [approximately 5 years]

      Collection of patient reported outcome questionnaires

    Other Outcome Measures

    1. To assess safety using a summary of adverse events. [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 [approximately 5 years]

      Serum concentrations of Durvalumab and Tremelimumab

    3. To assess immunogenicity of Durvalumab and Tremelimumab [approximately 5 years]

      Presence of anti-drug antibodies for Durvalumab and Tremelimumab

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 130 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
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    Sponsors and Collaborators

    • AstraZeneca

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    AstraZeneca
    ClinicalTrials.gov Identifier:
    NCT03682068
    Other Study ID Numbers:
    • D933SC00001
    First Posted:
    Sep 24, 2018
    Last Update Posted:
    Aug 19, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by AstraZeneca
    renal pelvis
    ureters
    urinary bladder
    urethra
    bladder cancer
    Additional relevant MeSH terms:
    Gemcitabine
    Carboplatin
    Durvalumab
    Tremelimumab

    Study Results

    No Results Posted as of Aug 19, 2022