Durvalumab or Placebo in Combination With Gemcitabine/Cisplatin in Patients With 1st Line Advanced Biliary Tract Cancer (TOPAZ-1)

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

7 Aug 2019 → ongoing

Decision date (initial)

2024-06-10

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

AstraZeneca AB

External identifiers

EU CT number

2023-507405-34-00

EudraCT number

2018-004688-30

ClinicalTrials.gov

NCT03875235

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To assess the efficacy of Arm A compared to Arm B in terms of OS in patients with first-line advanced BTC

Secondary objectives 6

1. To further assess the efficacy of Arm A compared To Arm B in terms of Progression-free survival (PFS), ORR (Objective response rate) , and Duration of response (DoR) in patients with first-line advanced BTC using Investigator assessments
2. To summarize the efficacy of Arm A compared To Arm B in terms of ORR and DoR in patients with first-line advanced BTC using BICR assessments
3. To assess disease-related symptoms, impacts, and HRQoL in patients treated with Arm A compared To Arm B
4. To assess the efficacy of Arm A compared To Arm B by PD-L1 expression
5. To assess the PK of durvalumab when used in combination with gemcitabine/cisplatin
6. To investigate the immunogenicity of durvalumab

Conditions and MedDRA coding

First-line patients with advanced biliary tract cancers (BTC)

Study design 2 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared. AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment https://vivli.org/. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Histologically confirmed, unresectable advanced or metastatic biliary tract, including cholangiocarcinoma (intrahepatic or extrahepatic) and gallbladder carcinoma.
2. Previously untreated disease if unresectable or metastatic at initial diagnosis
3. Recurrent disease >6 months after curative surgery or >6 months after the completion of adjuvant therapy (chemotherapy and/or radiation)
4. WHO/ECOG PS of 0 or 1

Exclusion criteria 5

1. History of another primary malignancy
2. Brain metastases or spinal cord compression
3. Uncontrolled intercurrent illness
4. Major surgical procedure within 28 days prior to the first dose of IP.
5. Prior locoregional therapy such as radioembolization

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall survival

Secondary endpoints 6

1. Progression-free survival (PFS), ORR (Objective response rate) , and Duration of response (DoR) according to RECIST 1.1using Investigator assessments
2. ORR and DoR according to RECIST 1.1 using BICR assessments
3. EORTC QLQ-C30: Global health status/QoL and impacts (eg, physical function); multi-term symptoms (eg, fatigue); and single items (eg, appetite loss, insomnia). EORTC QLQ-BIL21: Single-item symptoms (eg, abdominal pain [item 42], pruritus [item 36], jaundice [item 35])
4. Association of PD-L1 expression level with PFS, ORR, DoR, and DCR (Disease control rate) according to RECIST 1.1 using Investigator assessments and OS (Overall survival)
5. Serum concentration of durvalumab (peak and trough concentrations)
6. Presence of ADAs for durvalumab (confirmatory results: positive or negative)

Investigational products

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

Test 1

Comparator 2

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Astrazeneca AB

Sponsor organisation

Astrazeneca AB

Address

Astraallen Gartuna, Karlebyhus Byggnad 674 Karlebyhus Byggnad 674

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

4 EU/EEA countries · 14 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 24 files

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

Application history

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