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

• ClinicalTrials.gov Identifier: NCT03875235
• Recruitment Status: Active, not recruiting
• First Posted: March 14, 2019
• Last Update Posted: July 13, 2022
• Sponsor: AstraZeneca
• Information provided by (Responsible Party): AstraZeneca

Tracking Information

• First Submitted Date: March 13, 2019
• First Posted Date: March 14, 2019
• Last Update Posted Date: July 13, 2022
• Actual Study Start Date: April 16, 2019
• Actual Primary Completion Date: August 11, 2021 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: June 22, 2020): Overall survival [ Time Frame: 40 months ]

Original Primary Outcome Measures (submitted: March 13, 2019)

Overall survival [ Time Frame: 36 months ]

Assessments for Overall survival will be collected regularly at predefined time points until death

Current Secondary Outcome Measures (submitted: June 22, 2020)

• PFS according to RECIST 1.1 using investigator assessment [ Time Frame: 40 months ]
• ORR according to RECIST 1.1 using investigator assessment [ Time Frame: 40 months ]
• DoR according to RECIST 1.1 using investigator assessment [ Time Frame: 40 months ]
• EORTC QLQ-C30 and EORTC QLQ-BIL21 [ Time Frame: 40 months ]
• PFS, ORR, DoR, and DCR according to RECIST 1.1 using Investigator assessments and OS by PD-L1 expression [ Time Frame: 40 months ]
• Serum concentration of durvalumab (peak and trough concentration) [ Time Frame: 40 months ]
• Tiered results of ADAs for durvalumab [ Time Frame: 40 months ]

Original Secondary Outcome Measures (submitted: March 13, 2019)

• PFS accorridng RECSIST1.1 using investigator assessment [ Time Frame: 36 months ]
  Assessments will be made regularly until disease progression or until the end of the study
• ORR according to RECIST 1.1 using investigator assessment [ Time Frame: 36 months ]
  Assessments will be made regularly until disease progression or until the end of the study
• DoR accroding to RECSIST1.1 using investigator assessment [ Time Frame: 36 months ]
  Assessments will be made regularly until disease progression or until the end of the study

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Durvalumab or Placebo in Combination With Gemcitabine/Cisplatin in Patients With 1st Line Advanced Biliary Tract Cancer (TOPAZ-1)
• Official Title: A Phase III Randomized, Double-Blind Placebo Controlled, Multi-Regional, International Study of Durvalumab in Combination With Gemcitabine Plus Cisplatin Versus Placebo in Combination With Gemcitabine Plus Cisplatin for Patients With First-Line Advanced Biliary Tract Cancers
• Brief Summary: Durvalumab or Placebo in Combination With Gemcitabine/Cisplatin in Patients With 1st Line Advanced Biliary Tract Cancer (TOPAZ-1)
• Detailed Description: A Phase III Randomized, Double-Blind Placebo Controlled, Multi-Regional, International Study of Durvalumab in Combination with Gemcitabine Plus Cisplatin Versus Placebo in Combination with Gemcitabine Plus Cisplatin for Patients With First-Line Advanced Biliary Tract Cancers.
• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Durvalumab in Combination with Gemcitabine plus Cisplatin Placebo in Combination with Gemcitabine plus Cisplatin

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment

• Condition: Biliary Tract Neoplasms

Intervention

• Drug: Durvalumab
  IV infusion every 3 weeks with gemcitabine plus cisplatin up to 8 cycles followed by monotherapy every 4 weeks until disease progression or other discontinuation criteria.
• Drug: Placebo
  IV infusion every 3 weeks with gemcitabine plus cisplatin up to 8 cycles followed by monotherapy every 4 weeks until disease progression or other discontinuation criteria.

Study Arms

• Experimental: Treatment Arm
  Durvalumab + Gemcitabine + Cisplatin
  Intervention: Drug: Durvalumab
• Placebo Comparator: Placebo Arm
  Placebo + Gemcitabine + Cisplatin
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: January 12, 2022): 810
• Original Estimated Enrollment (submitted: March 13, 2019): 474
• Estimated Study Completion Date: March 31, 2025
• Actual Primary Completion Date: August 11, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion

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

Exclusion

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 130 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Bulgaria, Chile, China, France, Hong Kong, India, Italy, Japan, Korea, Republic of, Poland, Russian Federation, Taiwan, Thailand, Turkey, United Kingdom, United States

Administrative Information

• NCT Number: NCT03875235
• Other Study ID Numbers: D933AC00001
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• 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. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

• Current Responsible Party: AstraZeneca
• Original Responsible Party: Same as current
• Current Study Sponsor: AstraZeneca
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Gordon Cohen; AstraZeneca

• PRS Account: AstraZeneca
• Verification Date: July 2022