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

NCT03682068

Description:

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).

Related Conditions:
  • Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Study of Durvalumab Given With Chemotherapy, Durvalumab in Combination With Tremelimumab Given With Chemotherapy, or Chemotherapy in Patients With Unresectable Urothelial Cancer
  • 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.

Clinical Trial IDs

  • ORG STUDY ID: D933SC00001
  • NCT ID: NCT03682068

Conditions

  • Unresectable Locally Advanced Urothelial Cancer
  • Metastatic Urothelial Cancer

Interventions

DrugSynonymsArms
DurvalumabMEDI4736Durvalumab in Combination with SoC Chemotherapy
TremelimumabDurvalumab in Combination with Tremelimumab+SoC Chemotherapy
Cisplatin + GemcitabineDurvalumab in Combination with SoC Chemotherapy
Carboplatin + GemcitabineDurvalumab in Combination with SoC Chemotherapy

Purpose

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).

Trial Arms

NameTypeDescriptionInterventions
Durvalumab in Combination with SoC ChemotherapyExperimentalDurvalumab 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
  • Durvalumab
  • Cisplatin + Gemcitabine
  • Carboplatin + Gemcitabine
Durvalumab in Combination with Tremelimumab+SoC ChemotherapyExperimentalDurvalumab 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
  • Durvalumab
  • Tremelimumab
  • Cisplatin + Gemcitabine
  • Carboplatin + Gemcitabine
SoC ChemotherapyActive ComparatorPatients 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
  • Cisplatin + Gemcitabine
  • Carboplatin + Gemcitabine

Eligibility Criteria

        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
      
Maximum Eligible Age:130 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Survival (OS)
Time Frame:approximately 5 years
Safety Issue:
Description:OS is defined as the time from the date of randomization until death due to any cause

Secondary Outcome Measures

Measure:Overall Survival (OS)
Time Frame:approximately 5 years
Safety Issue:
Description:Additional analysis beyond the primary endpoint
Measure:Overall Survival at 24 months (OS24)
Time Frame:24 months
Safety Issue:
Description:The OS24 will be defined as the Kaplan-Meier estimate of OS at 24 months
Measure:Progression Free Survival (PFS)
Time Frame:approximately 5 years
Safety Issue:
Description: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
Measure:Alive and Progression Free Survival at 12 months (APF12)
Time Frame:12 months
Safety Issue:
Description:The APF12 will be defined as the Kaplan-Meier estimate of PFS (per RECIST 1.1) at 12 months
Measure:Objective Response Rate (ORR)
Time Frame:approximately 5 years
Safety Issue:
Description: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
Measure:Duration of Response (DoR)
Time Frame:approximately 5 years
Safety Issue:
Description: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
Measure:Disease Control Rate (DCR)
Time Frame:approximately 5 years
Safety Issue:
Description: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
Measure:Time from randomization to second (PFS2)
Time Frame:approximately 5 years
Safety Issue:
Description: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
Measure:To assess disease-related symptoms, physical functioning, and other Health-related quality of life
Time Frame:approximately 5 years
Safety Issue:
Description:Collection of patient reported outcome questionnaires

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:AstraZeneca

Trial Keywords

  • renal pelvis
  • ureters
  • urinary bladder
  • urethra
  • bladder cancer

Last Updated

January 6, 2021