A trial to learn how well durvalumab and chemotherapy with or without tremelimumab work in adults with advanced cancer of the bladder or urinary system

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AstraZeneca AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

30 Nov 2018 → ongoing

Decision date (initial)

2024-07-01

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AstraZeneca AB

External identifiers

EU CT number

2024-510976-19-00

EudraCT number

2018-001883-48

ClinicalTrials.gov

NCT03682068

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To assess the efficacy of durvalumab + SoC combination therapy versus SoC in terms of OS in patients with unresectable locally advanced or metastatic UC and high PD-L1 expression.

To assess the efficacy of Durvalumab and Tremelimumab + SoC combination therapy versus SoC in terms of OS in patients with unresectable locally advanced or metastatic UC and high PD-L1 expression.

Secondary objectives 2

1. To assess the efficacy in patients in different treatment arms
2. To assess disease-related symptoms, safety, physical functioning, and other health related quality of life in patients in different treatment arms

Conditions and MedDRA coding

Patients with Unresectable Locally Advanced or Metastatic Urothelial Cancer

Study design 3 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. 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)
2. 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].
3. At least 1 lesion, not previously irradiated, that qualifies as a RECIST 1.1 target lesion at baseline.
4. World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 at enrolment
5. Adequate organ and marrow function as defined in the protocol
6. Life expectancy ≥12 weeks in the opinion of the investigator
7. Evidence of post-menopausal status, or negative urinary or serum pregnancy test for female pre-menopausal patients.

Exclusion criteria 5

1. 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.
2. No severe concomitant condition that requires immunosuppression medication
3. Untreated central nervous system (CNS) metastases and/or carcinomatous meningitis
4. Patients who may be eligible for or are being considered for radical resection during the course of the study.
5. 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall Survival (OS)

Secondary endpoints 1

1. Progression Free Survival (PFS) - Overall Survival (OS) - Alive and Progression Free Patients at 12 Months (APF12) - Overall Response Rate (ORR) - Disease Control Rate (DCR) - Duration of Response (DoR) - Time from Randomization to Second Progression PFS (PFS2) - Safety - Disease related symptoms

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Comparator 4

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AstraZeneca AB

Sponsor organisation

AstraZeneca AB

Address

-

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Public contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Locations

6 EU/EEA countries · 43 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 47 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

10 submissions — initial application plus substantial / non-substantial modifications