Clinical Trials /

Study of MEDI4736 (Durvalumab) With or Without Tremelimumab Versus Standard of Care Chemotherapy in Urothelial Cancer

NCT02516241

Description:

A Phase III, Randomized, Open-Label, Controlled, Multi-Center, Global Study of First-Line MEDI4736 (Durvalumab) Monotherapy and MEDI4736 (Durvalumab) in Combination with Tremelimumab Versus Standard of Care Chemotherapy in Patients with Stage IV Urothelial Cancer

Related Conditions:
  • Urothelial Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Study of MEDI4736 (Durvalumab) With or Without Tremelimumab Versus Standard of Care Chemotherapy in Urothelial Cancer
  • Official Title: A Phase III, Randomized, Open-Label, Controlled, Multi-Center, Global Study of First-Line MEDI4736 (Durvalumab) Monotherapy and MEDI4736 (Durvalumab) in Combination With Tremelimumab Versus Standard of Care Chemotherapy in Patients With Unresectable Stage IV Urothelial Cancer

Clinical Trial IDs

  • ORG STUDY ID: D419BC00001
  • NCT ID: NCT02516241

Conditions

  • Urothelial Cancer

Interventions

DrugSynonymsArms
MEDI4736 (Durvalumab)Combination Therapy
TremelimumabCombination Therapy
CisplatinStandard of Care
CarboplatinStandard of Care
GemcitabineStandard of Care

Purpose

A Phase III, Randomized, Open-Label, Controlled, Multi-Center, Global Study of First-Line MEDI4736 (Durvalumab) Monotherapy and MEDI4736 (Durvalumab) in Combination with Tremelimumab Versus Standard of Care Chemotherapy in Patients with Stage IV Urothelial Cancer

Detailed Description

      This is a randomized, open-label, controlled, multi-center, global Phase III study to
      determine the efficacy and safety of MEDI4736 (Durvalumab) monotherapy and MEDI4736
      (Durvalumab) in combination with tremelimumab versus SoC (cisplatin + gemcitabine or
      carboplatin + gemcitabine doublet) first-line chemotherapy in treatment-naïve patients with
      histologically or cytologically documented, unresectable, Stage IV transitional cell
      carcinoma (transitional cell and mixed transitional/non-transitional cell histologies) of the
      urothelium (including renal pelvis, ureters, urinary bladder, and urethra) and to allow
      sufficient flexibility for Investigators and patients to select the agents that reflect their
      normal clinical practice and national guidelines. The patients enrolled in the study will be
      randomized 1:1:1 to receive treatment with combination therapy, monotherapy, or SoC
      (cisplatin + gemcitabine or carboplatin + gemcitabine, based on cisplatin eligibility).
      Patients will be treated with MEDI4736 (Durvalumab) or MEDI4736 (Durvalumab) with
      tremelimumab, or treated with SoC until progressive disease (PD) is confirmed, unacceptable
      toxicity occurs, withdrawal of consent, or another discontinuation criterion is met. Patients
      will be followed for up to 2 years.
    

Trial Arms

NameTypeDescriptionInterventions
Combination TherapyExperimentalMEDI4736 (Durvalumab) + Tremelimumab
  • MEDI4736 (Durvalumab)
  • Tremelimumab
MonotherapyExperimentalMEDI4736 (Durvalumab)
  • MEDI4736 (Durvalumab)
Standard of CareActive ComparatorStandard of Care Chemotherapy Treatment
  • Cisplatin
  • Carboplatin
  • Gemcitabine

Eligibility Criteria

        Inclusion Criteria:

          -  Patients with histologically or cytologically documented, unresectable, Stage IV
             transitional cell carcinoma of the urothelium who have not been previously treated
             with first-line chemotherapy.

          -  Patients eligible or ineligible for cisplatin-based chemotherapy. Cisplatin
             ineligibility is defined as meeting 1 of the following criteria: • Creatinine
             clearance (calculated or measured) <60 mL/min calculated by Cockcroft-Gault equation
             (using actual body weight) or by measured 24-hour urine collection for determination •
             Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥2 audiometric hearing
             loss • CTCAE Grade ≥2 peripheral neuropathy • New York Heart Association ≥Class III
             heart failure.

          -  Tumor PD-L1 status, with Immunohistochemical (IHC) assay confirmed by a reference
             laboratory, must be known prior to randomization.

        Exclusion Criteria:

          -  Prior exposure to immune-mediated therapy, including but not limited to, other anti
             cytotoxic T-lymphocyte-associated protein 4 (CTLA 4), anti-PD-1, anti-PD-L1, or
             anti-PD-L2 antibodies, including therapeutic anticancer vaccines. Prior local
             intervesical chemotherapy or immunotherapy is allowed if completed at least 28 days
             prior to the initiation of study treatment.

          -  History of allogenic organ transplantation that requires use of immunosuppressive
             agents.

          -  Active or prior documented autoimmune or inflammatory disorders. The following are
             exceptions to this criterion: • Patients with vitiligo or alopecia • Patients with
             hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement • Any
             chronic skin condition that does not require systemic therapy • Patients without
             active disease in the last 3 years may be included but only after consultation with
             AstraZeneca • Patients with celiac disease controlled by diet alone may be included
             but only after consultation with AstraZeneca.

          -  Brain metastases or spinal cord compression unless the patient's condition is stable
             and off steroids for at least 14 days prior to the start of study treatment. Patients
             with suspected or known brain metastases at screening should have an MRI
             (preferred)/CT, preferably with IV contrast to access baseline disease status.

          -  Active infection including tuberculosis, hepatitis B, hepatitis C, or human
             immunodeficiency virus (HIV).

          -  Current or prior use of immunosuppressive medication within 14 days before the first
             dose of investigational product (IP). 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, CT scan premedication).

          -  Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note:
             Patients, if enrolled, should not receive live vaccine during the study and up to 30
             days after the last dose of IP.
      
Maximum Eligible Age:130 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:To assess the efficacy of MEDI4736 + tremelimumab combination therapy versus SoC in terms of OS in patients with unresectable Stage IV UC
Time Frame:Up to 4 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:To assess the efficacy of MEDI4736 monotherapy compared to SoC in terms of PFS in patients with PD-L1-High UC
Time Frame:4 years
Safety Issue:
Description:
Measure:To assess the efficacy of MEDI4736 + tremelimumab combination therapy versus SoC in terms of PFS in patients with UC
Time Frame:4 years
Safety Issue:
Description:
Measure:To further assess the efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of ORR
Time Frame:4 years
Safety Issue:
Description:
Measure:To further assess the efficacy of MEDI4736 monotherapy compared to SoC in terms of ORR
Time Frame:4 years
Safety Issue:
Description:
Measure:To assess disease-related symptoms and HRQoL in UC patients treated with MEDI4736 monotherapy and MEDI4736 + tremelimumab combination therapy compared with SoC and each other using the FACT-BL questionnaire
Time Frame:4 years
Safety Issue:
Description:
Measure:To assess the serum concentration of MEDI4736/tremelimumab of MEDI4736 monotherapy and MEDI4736 + tremelimumab combination therapy
Time Frame:up to 6 months
Safety Issue:
Description:
Measure:To investigate the immunogenicity of MEDI4736 monotherapy and MEDI4736 + tremelimumab combination therapy
Time Frame:4 years
Safety Issue:
Description:
Measure:To assess the objective response rate (ORR) of MEDI4736 monotherapy in patients who are not cisplatin-eligible
Time Frame:4 years
Safety Issue:
Description:
Measure:To assess the duration of response (DoR) of MEDI4736 monotherapy in patients who are not cisplatin-eligible
Time Frame:4 years
Safety Issue:
Description:

Details

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

Trial Keywords

  • Urothelial Cancer
  • Phase III

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