ClinicalTrials.gov

History of Changes for Study: NCT02516241
Study of MEDI4736 With or Without Tremelimumab Versus Standard of Care Chemotherapy in Bladder Cancer
Latest version (submitted November 2, 2022) on ClinicalTrials.gov
  • A study version is represented by a row in the table.
  • Select two study versions to compare. One each from columns A and B.
  • Choose either the "Merged" or "Side-by-Side" comparison format to specify how the two study versions are to be displayed. The Side-by-Side format only applies to the Protocol section of the study.
  • Click "Compare" to do the comparison and show the differences.
  • Select a version's Submitted Date link to see a rendering of the study for that version.
  • The yellow A/B choices in the table indicate the study versions currently compared below. A yellow table row indicates the study version currently being viewed.
  • Hover over the "Recruitment Status" to see how the study's recruitment status changed.
  • Study edits or deletions are displayed in red.
  • Study additions are displayed in green.
Study Record Versions
Version A B Submitted Date Changes
1 August 4, 2015 None (earliest Version on record)
2 November 30, 2015 Recruitment Status, Study Status, Contacts/Locations, Eligibility, Arms and Interventions and Oversight
3 December 30, 2015 Study Status
4 January 29, 2016 Study Status
5 February 29, 2016 Study Status
6 March 29, 2016 Study Status
7 June 14, 2016 Study Status
8 July 13, 2016 Study Status
9 August 9, 2016 Study Status and Study Identification
10 September 1, 2016 Outcome Measures, Study Status, Contacts/Locations, Conditions, Study Description, Study Identification, Eligibility and Study Design
11 October 3, 2016 Contacts/Locations and Study Status
12 November 2, 2016 Study Status, Contacts/Locations and Eligibility
13 November 29, 2016 Contacts/Locations and Study Status
14 December 21, 2016 Contacts/Locations and Study Status
15 January 19, 2017 Contacts/Locations and Study Status
16 February 15, 2017 Study Status, Contacts/Locations and Eligibility
17 March 27, 2017 Contacts/Locations and Study Status
18 June 13, 2017 Contacts/Locations and Study Status
19 July 10, 2017 Contacts/Locations and Study Status
20 August 16, 2017 Contacts/Locations and Study Status
21 December 5, 2017 Outcome Measures, Contacts/Locations, Study Status, Arms and Interventions, Study Description, Study Identification and Study Design
22 January 4, 2018 Study Status and Contacts/Locations
23 February 7, 2018 Contacts/Locations and Study Status
24 March 19, 2018 Contacts/Locations and Study Status
25 April 27, 2018 Contacts/Locations and Study Status
26 May 28, 2018 Contacts/Locations and Study Status
27 June 28, 2018 Contacts/Locations and Study Status
28 July 27, 2018 Study Status and Contacts/Locations
29 August 22, 2018 Contacts/Locations and Study Status
30 October 10, 2018 Contacts/Locations and Study Status
31 November 19, 2018 Contacts/Locations and Study Status
32 January 11, 2019 Contacts/Locations and Study Status
33 February 25, 2019 Contacts/Locations and Study Status
34 March 26, 2019 Study Status and Contacts/Locations
35 April 29, 2019 Contacts/Locations and Study Status
36 June 12, 2019 Study Status
37 July 9, 2019 Contacts/Locations and Study Status
38 August 7, 2019 Contacts/Locations and Study Status
39 September 5, 2019 Contacts/Locations and Study Status
40 January 29, 2020 Recruitment Status, Contacts/Locations, Study Status and Study Design
41 May 20, 2020 Study Status
42 July 6, 2020 Study Status, Outcome Measures, Contacts/Locations, IPDSharing and Study Design
43 July 9, 2020 Study Status
44 October 26, 2020 Contacts/Locations, Study Status and Study Design
Show
Results Submission Events
45 April 21, 2021 Outcome Measures, Study Status, Contacts/Locations, Document Section, Results and References
46 August 16, 2021 Contacts/Locations and Study Status
47 September 1, 2021 Study Status and Contacts/Locations
48 December 2, 2021 Contacts/Locations and Study Status
49 March 22, 2022 Contacts/Locations and Study Status
50 July 14, 2022 Study Status
51 November 2, 2022 Study Status
Comparison Format:

Scroll up to access the controls

Study NCT02516241
Submitted Date:  August 4, 2015 (v1)

Open or close this module Study Identification
Unique Protocol ID: D419BC00001
Brief Title: Study of MEDI4736 With or Without Tremelimumab Versus Standard of Care Chemotherapy in Bladder Cancer
Official Title: A Phase III, Randomized, Open-label, Controlled, Multi-Center, Global Study of First-Line MEDI4736 Monotherapy and MEDI4736 in Combination With Tremelimumab Versus Standard of Care Chemotherapy in Patients With Unresectable Stage IV Urothelial Bladder Cancer
Secondary IDs:
Open or close this module Study Status
Record Verification: August 2015
Overall Status: Not yet recruiting
Study Start: October 2015
Primary Completion: November 2017 [Anticipated]
Study Completion: August 2019 [Anticipated]
First Submitted: July 13, 2015
First Submitted that
Met QC Criteria:
August 4, 2015
First Posted: August 5, 2015 [Estimate]
Last Update Submitted that
Met QC Criteria:
August 4, 2015
Last Update Posted: August 5, 2015 [Estimate]
Open or close this module Sponsor/Collaborators
Sponsor: AstraZeneca
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug:
U.S. FDA-regulated Device:
Data Monitoring: Yes
Open or close this module Study Description
Brief Summary: A Phase III, Randomized, Open-label, Controlled, Multi-Center, Global Study of First-Line MEDI4736 Monotherapy and MEDI4736 in Combination with Tremelimumab Versus Standard of Care Chemotherapy in Patients with Stage IV Urothelial Bladder Cancer
Detailed Description: This is a randomized, open-label, controlled, multi-center, global Phase III study to determine the efficacy and safety of MEDI4736 monotherapy and MEDI4736 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. The patients will be randomized in a 1:1:1 ratio to receive treatment with combination therapy, monotherapy, or SoC (cisplatin + gemcitabine or carboplatin + gemcitabine, based on cisplatin eligibility). Patients will be treated with MEDI4736 or MEDI4736 with tremelimumab for up to 12 months or with SoC for up to 6 months. Patients will be followed for up to 2 years.
Open or close this module Conditions
Conditions: Bladder Cancer
Keywords: Bladder Cancer
Phase III
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 3
Interventional Study Model: Parallel Assignment
Number of Arms: 3
Masking: None (Open Label)
Allocation: Randomized
Enrollment: 525 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Combination Therapy Drug: MEDI4736
IV infusion
Drug: Tremelimumab
IV infusion
Experimental: Monotherapy Drug: MEDI4736
IV infusion
Active Comparator: Standard of Care Drug: Cisplatin
IV infusion
Drug: Carboplatin
IV infusion
Drug: Gemcitabine
IV infusion
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Progression-free survival (PFS)
[ Time Frame: Up to 3 years ]

To assess PFS of MEDI4736 in combination with tremelimumab to standard of care (SoC) chemotherapy
Secondary Outcome Measures:
1. PFS in programmed death-ligand 1 (PD-L1)-negative patients
[ Time Frame: Up to 3 years ]

To assess PFS of MEDI4736 + tremelimumab to SoC chemotherapy, and to monotherapy in patients with PD-L1-negative
2. Overall survival (OS)
[ Time Frame: Up to 4 years ]

To assess OS of MEDI4736 + tremelimumab to SoC chemotherapy
3. Objective response rate (ORR)
[ Time Frame: Up to 3 years ]

To further assess ORR of MEDI4736 + tremelimumab to SoC chemotherapy
4. Functional Assessment of Cancer Therapy - Bladder Cancer (FACT-BL)
[ Time Frame: Up to 3 years ]

To assess disease-related symptoms
5. Anti-drug Antibodies (ADAs)
[ Time Frame: Up to 1 year ]

To investigate the immunogenicity of monotherapy and MEDI4736 + tremelimumab
6. Incidence of adverse events
[ Time Frame: Up to 15 months ]

To assess the safety and tolerability
7. PFS
[ Time Frame: Up to 3 years ]

To assess PFS of MEDI4736 monotherapy to SoC chemotherapy
8. Pharmacokinetics of tremelimumab: Peak concentration (Cmax)
[ Time Frame: Up to 1 year ]

Peak concentration in MEDI4736 + tremelimumab combination therapy
9. Pharmacokinetics of MEDI4736: Trough concentration (Ctrough)
[ Time Frame: Up to 1 year ]

Trough concentration in MEDI4736 monotherapy and in combination with tremelimumab
10. Pharmacokinetics of tremelimumab: Trough concentration (Ctrough)
[ Time Frame: Up to 1 year ]

Trough concentration in MEDI4736 + tremelimumab combination therapy
11. Pharmacokinetics of MEDI4736: Peak concentration (Cmax)
[ Time Frame: Up to 1 year ]

Peak concentration in MEDI4736 monotherapy and in combination with tremelimumab
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
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
    • 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.
  • History of allogenic organ transplantation that requires use of immunosuppressive agents.
  • Active or prior documented autoimmune or inflammatory disorders within the past 3 years prior to the start of treatment.
  • The following are exceptions to this criterion:
    • Patients with vitiligo or alopecia
    • Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement of psoriasis not requiring systemic treatment.
  • Brain metastases or spinal cord compression. Patients with suspected brain metastases at screening should have a CT/ MRI of the brain prior to study entry.
  • Active infection including hepatitis B, hepatitis C, or human immunodeficiency virus (HIV).
  • Current or prior use of immunosuppressive medication within 14 days before the first dose of MEDI4736 or tremelimumab.
  • 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 investigational product (IP).
Open or close this module Contacts/Locations
Central Contact Person: AstraZeneca Clinical Study Information Center
Telephone: 1-877-240-9479
Email: information.center@astrazeneca.com
Locations: Italy
Research Site
Milano, Italy
Korea, Republic of
Research Site
Seoul, Korea, Republic of
Spain
Research Site
Badajoz, Spain
Research Site
Badalona(Barcelona), Spain
Research Site
Barcelona, Spain
Research Site
Elche(Alicante), Spain
Research Site
Madrid, Spain
Research Site
Santiago de Compostela(A Coru, Spain
Open or close this module IPDSharing
Plan to Share IPD:
Open or close this module References
Links:
Available IPD/Information:

Scroll up to access the controls Scroll to the Study top

U.S. National Library of Medicine | U.S. National Institutes of Health | U.S. Department of Health & Human Services