Study of Durvalumab Given with Chemotherapy, Durvalumab in Combination with Tremelimumab Given with Chemotherapy, or Chemotherapy in Patients with Unresectable Urothelial Cancer - NILE

Study identifier:D933SC00001

ClinicalTrials.gov identifier:NCT03682068

EudraCT identifier:2018-001883-48

CTIS identifier:2024-510976-19-00

Recruitment Complete

Official Title

A Phase III, Randomized, Open-Label, Controlled, Multi-Center, Global Study of First-Line Durvalumab in Combination with Standard of Care Chemotherapy and Durvalumab in Combination with Tremelimumab and Standard of Care Chemotherapy Versus Standard of Care Chemotherapy Alone in Patients with Unresectable Locally Advanced or Metastatic Urothelial Cancer.

Medical condition

Unresectable Locally Advanced Urothelial Cancer

Phase

Phase 3

Healthy volunteers

Study drug

Durvalumab, Tremelimumab, Cisplatin + Gemcitabine, Carboplatin + Gemcitabine

Sex

All

Actual Enrollment

1246

Study type

Interventional

Age

18 Years - 130 Years

Date

Study Start Date: 27 Sept 2018

Estimated Primary Completion Date: 30 Jun 2025

Estimated Study Completion Date: 30 Jun 2025

Study design

Allocation: Randomized
Endpoint Classification: -
Intervention Model: Parallel Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Sept 2024 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Inclusion Criteria

-Patients with histologically or cytologically documented, unresectable, locally advanced or metastatic transitional cell carcinoma (transitional cell and mixed transitional/non-transitional cell histologies) of the urothelium (including renal pelvis, ureters, urinary bladder, and urethra)
-Patients who have not been previously treated with first-line chemotherapy. Patients who have received prior definitive chemoradiation, adjuvant or neoadjuvant treatment for locally advanced disease are eligible provided that progression to locally advanced or metastatic disease has occurred >12 months from the last therapy [for chemoradiation and adjuvant treatment] or >12 months from the last surgery [for neoadjuvant treatment].
-At least 1 lesion, not previously irradiated, that qualifies as a RECIST 1.1 target lesion at baseline.
- World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 at enrolment
-Adequate organ and marrow function as defined in the protocol
- Life expectancy ≥12 weeks in the opinion of the investigator
-Evidence of post-menopausal status, or negative urinary or serum pregnancy test for female pre-menopausal patients.

Exclusion Criteria

- 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, except therapeutic anticancer vaccines, which are permitted. Prior local intervesical chemotherapy or immunotherapy is allowed if completed at least 28 days prior to the initiation of study treatment.
- No severe concomitant condition that requires immunosuppression medication
- Untreated central nervous system (CNS) metastases and/or carcinomatous meningitis
- Patients who may be eligible for or are being considered for radical resection during the course of the study.
- Any medical contraindications to platinum (cisplatin or carboplatin) based doublet chemotherapy and/or known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients

No locations available

Arms	Assigned Interventions
Experimental: Durvalumab in Combination with SoC Chemotherapy Durvalumab every 3 weeks in concurrence with chemotherapy, followed by durvalumab monotherapy every 4 weeks. All patients will receive one of the following standard of care chemotherapy regimens every 3 weeks for 6 cycles: - cisplatin+ gemcitabine - If the patient is cisplatin-ineligible, carboplatin + gemcitabine	Drug: Durvalumab Durvalumab IV (intravenous infusion) Other Name: MEDI4736 Drug: Cisplatin + Gemcitabine Cisplatin IV (intravenous)+ Gemcitabine IV(intravenous), as standard of care. Drug: Carboplatin + Gemcitabine Carboplatin IV (intravenous)+ Gemcitabine IV(intravenous), as standard of care.
Experimental: Durvalumab in Combination with Tremelimumab+SoC Chemotherapy Durvalumab and Tremelimumab every 3 weeks in concurrence with chemotherapy, followed by durvalumab monotherapy every 4 weeks Tremelimumab will be provided for 4 cycles. All patients will receive one of the following standard of care chemotherapy regimens every 3 weeks for 6 cycles: - cisplatin+ gemcitabine - If the patient is cisplatin-ineligible, carboplatin + gemcitabine	Drug: Durvalumab Durvalumab IV (intravenous infusion) Other Name: MEDI4736 Drug: Tremelimumab Tremelimumab IV (intravenous infusion) Drug: Cisplatin + Gemcitabine Cisplatin IV (intravenous)+ Gemcitabine IV(intravenous), as standard of care. Drug: Carboplatin + Gemcitabine Carboplatin IV (intravenous)+ Gemcitabine IV(intravenous), as standard of care.
Active Comparator: SoC Chemotherapy Patients will receive one of the following standard of care chemotherapy regimens every 3 weeks for 6 cycles: - cisplatin+ gemcitabine - If the patient is cisplatin-ineligible, carboplatin + gemcitabine	Drug: Cisplatin + Gemcitabine Cisplatin IV (intravenous)+ Gemcitabine IV(intravenous), as standard of care. Drug: Carboplatin + Gemcitabine Carboplatin IV (intravenous)+ Gemcitabine IV(intravenous), as standard of care.

Documents available

Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

[email protected]