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 Cancer
- Conditions
- urothelial cancer10038364
- Registration Number
- NL-OMON50230
- Lead Sponsor
- Astra Zeneca
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 70
1. Age *18 years at the time of screening.
2. Written informed consent
3. 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.
4. At least 1 lesion, not previously irradiated, that can be accurately
measured at
baseline as *10 mm in the longest diameter with a computed tomography (CT) or
magnetic resonance imaging (MRI) and that is suitable for accurate repeated
measurements as per
Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1)
guidelines.
5. Eastern Cooperative Oncology Group (ECOG) PS 0 or 1
6. Life expectancy *12 weeks (in the opinion of the Investigator)
7. Patients eligible or ineligible for cisplatin-based chemotherapy.
8. Tumor PD-L1 status, with IHC assay confirmed by a reference laboratory, must
be
known prior to randomization.
9. Adequate organ and marrow function
1. Involvement in the planning and/or conduct of the study
2. Previous IP assignment in the present study
3. Concurrent enrollment in another clinical study, unless it is an
observational (noninterventional) clinical study or during the follow-up period
of an interventional study
4. 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, 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
5. Any unresolved toxicity NCI CTCAE Grade *2 from previous anticancer therapy
with the exception of alopecia, vitiligo, and the laboratory values defined in
the inclusion criteria.
6. Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer
treatment. Concurrent use of hormonal therapy for non-cancer-related conditions
(eg, hormone replacement therapy) is acceptable.
7. Radiotherapy treatment to more than 30% of the bone marrow or with a wide
field of radiation within 28 days of the first dose of study drug.
8. Major surgical procedure (as defined by the Investigator) within 28 days
prior to the first dose of IP.
9. History of allogenic organ transplantation that requires use of
immunosuppressive agents.
10. Active or prior documented autoimmune or inflammatory disorders
11. Uncontrolled intercurrent illnesses.
12. Other malignancy within 5 years before first dose of IP, except for the
following pending a discussion with AstraZeneca: Patients with a history of
prostate cancer and patients who have been adequately treated for a malignancy
with a low potential risk for recurrence.
13. History of leptomeningeal carcinomatosis
14. Brain metastases or spinal cord compression.
15. QT interval corrected for heart rate *470 ms calculated from 3 ECGs.
16. History of active primary immunodeficiency
17. Active infection, including tuberculosis, hepatitis B, hepatitis C, or
human immunodeficiency virus.
18. Current or prior use of immunosuppressive medication within 14 days before
the
first dose of IP.
19. Receipt of live attenuated vaccine within 30 days prior to the first dose
of IP.
20. Female patients who are pregnant or breastfeeding or male or female
patients of reproductive potential who are not willing to employ effective
birth control from screening to 90 days after the last dose of MEDI4736
monotherapy or 180 days after the last dose of MEDI4736 + tremelimumab
combination therapy
21. Known allergy or hypersensitivity to IP or any IP excipient, or to other
humanized mAbs
22. Any medical contraindication to platinum (cisplatin or carboplatin)-based
doublet chemotherapy
23. Patient <30 kg in weight
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>To assess the efficacy of MEDI4736 + tremelimumab combination therapy versus<br /><br>SoC in terms of OS in patients with unresectable Stage IV UC<br /><br><br /><br>To assess the efficacy of MEDI4736 monotherapy versus SoC in terms of OS in<br /><br>patients with unresectable Stage IV PD L1 High UC</p><br>
- Secondary Outcome Measures
Name Time Method