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

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ClinicalTrials.gov Identifier: NCT02516241
Recruitment Status : Recruiting
First Posted : August 5, 2015
Last Update Posted : January 5, 2018
Sponsor:
Information provided by (Responsible Party):

Study Description
Brief Summary:
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

Condition or disease Intervention/treatment Phase
Urothelial Cancer Drug: MEDI4736 (Durvalumab) Drug: Tremelimumab Drug: Cisplatin Drug: Carboplatin Drug: Gemcitabine Phase 3

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.

Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1200 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 MEDI4736 (Durvalumab) Monotherapy and MEDI4736 (Durvalumab) in Combination With Tremelimumab Versus Standard of Care Chemotherapy in Patients With Unresectable Stage IV Urothelial Cancer
Actual Study Start Date : November 2, 2015
Estimated Primary Completion Date : September 23, 2019
Estimated Study Completion Date : September 23, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Durvalumab
U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: Combination Therapy
MEDI4736 (Durvalumab) + Tremelimumab
Drug: MEDI4736 (Durvalumab)
IV infusion
Drug: Tremelimumab
IV infusion
Experimental: Monotherapy
MEDI4736 (Durvalumab)
Drug: MEDI4736 (Durvalumab)
IV infusion
Active Comparator: Standard of Care
Standard of Care Chemotherapy Treatment
Drug: Cisplatin
IV infusion
Drug: Carboplatin
IV infusion
Drug: Gemcitabine
IV infusion


Outcome Measures

Primary Outcome Measures :
  1. 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 ]
  2. To assess the efficacy of MEDI4736 monotherapy versus SoC in terms of OS in patients with unresectable Stage IV PD-L1- High UC [ Time Frame: up to 4 years ]

Secondary Outcome Measures :
  1. 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 ]
  2. To assess the efficacy of MEDI4736 + tremelimumab combination therapy versus SoC in terms of PFS in patients with UC [ Time Frame: 4 years ]
  3. To further assess the efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of ORR [ Time Frame: 4 years ]
  4. To further assess the efficacy of MEDI4736 monotherapy compared to SoC in terms of ORR [ Time Frame: 4 years ]
  5. 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 ]
  6. To assess the serum concentration of MEDI4736/tremelimumab of MEDI4736 monotherapy and MEDI4736 + tremelimumab combination therapy [ Time Frame: up to 6 months ]
  7. To investigate the immunogenicity of MEDI4736 monotherapy and MEDI4736 + tremelimumab combination therapy [ Time Frame: 4 years ]
  8. To assess the objective response rate (ORR) of MEDI4736 monotherapy in patients who are not cisplatin-eligible [ Time Frame: 4 years ]
  9. To assess the duration of response (DoR) of MEDI4736 monotherapy in patients who are not cisplatin-eligible [ Time Frame: 4 years ]

Other Outcome Measures:
  1. To use summary of adverse events to assess the safety of MEDI4736 monotherapy and MEDI4736 + tremelimumab combination therapy compared to SoC [ Time Frame: 4 years ]
    AEs (both in terms of MedDRA preferred terms and CTCAE grade) will be listed individually by patient. The number of patients experiencing each AE will be summarized by treatment arm and CTCAE grade.


Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 130 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02516241


Contacts
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com
Contact: AstraZeneca Cancer Study Locator Service 1-877-400-4656 AstraZeneca@emergingmed.com

  Show 261 Study Locations
Sponsors and Collaborators
AstraZeneca
More Information

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02516241     History of Changes
Other Study ID Numbers: D419BC00001
First Posted: August 5, 2015    Key Record Dates
Last Update Posted: January 5, 2018
Last Verified: January 2018

Keywords provided by AstraZeneca:
Urothelial Cancer
Phase III

Additional relevant MeSH terms:
Gemcitabine
Tremelimumab
Carboplatin
Antibodies, Monoclonal
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs