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 : September 6, 2019
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Urothelial Cancer | Drug: MEDI4736 (Durvalumab) Drug: Tremelimumab Drug: Cisplatin Drug: Carboplatin Drug: Gemcitabine | Phase 3 |
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 |

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

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Ages Eligible for Study: | 18 Years to 130 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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.

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
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 |

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: | September 6, 2019 |
Last Verified: | September 2019 |
Urothelial Cancer Phase III |
Gemcitabine Carboplatin Durvalumab Tremelimumab Antibodies, Monoclonal Antineoplastic Agents Antimetabolites, Antineoplastic Antimetabolites |
Molecular Mechanisms of Pharmacological Action Antiviral Agents Anti-Infective Agents Enzyme Inhibitors Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antineoplastic Agents, Immunological |