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Neoadjuvant Gemcitabine Plus Cisplatin With or Without Durvalumab in Resectable Biliary Tract Cancer (DEBATE)

Primary Purpose

Biliary Tract Neoplasms, Gallbladder Cancer, Cholangiocarcinoma

Status
Active
Phase
Phase 2
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Durvalumab + Gem/Cis
Gem/Cis
Sponsored by
Asan Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Biliary Tract Neoplasms focused on measuring Biliary tract cancer, Immunotherapy, Neoadjuvant chemotherapy

Eligibility Criteria

19 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
  • Age > 19 years at time of study entry
  • Histologically confirmed adenocarcinoma of biliary tract (intrahepatic, hilar or extrahepatic cholangiocarcinoma, or gallbladder carcinoma).
  • Localized, potentially resectable, non-metastatic disease (determined at the discretion of attending surgeons) based on the results of CT, MRI or PET-CT scans.
  • No active uncontrolled infection, except chronic viral hepatitis under antiviral therapy.
  • Eastern Cooperative Oncology Group (ECOG performance status of 0 or 1
  • Body weight >30kg
  • Adequate normal organ and marrow function
  • Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
  • No other malignant disease apart from non-melanotic skin cancer, carcinoma in situ of the uterine cervix, localized prostate or papillary thyroid cancer, or any other cancer where treated with curative intent > 5 years previously without evidence of relapse

Exclusion Criteria:

  • Medical or psychiatric conditions that compromise the patient's ability to give informed consent or to complete the protocol or a history of non-compliance
  • Obstruction of gastrointestinal tract
  • Active gastrointestinal bleeding
  • Myocardial infarction within 6 months prior to the study medication, and other clinically significant heart disease (e.g., unstable angina, congestive heart failure or uncontrolled hypertension)
  • Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the investigator's opinion makes it undesirable for the patient to participate in the study or which would jeopardise compliance with the protocol
  • Combined hepatocellular carcinoma/cholangiocarcinoma is excluded.
  • History of allogenic organ transplantation.
  • History of another primary malignancy except for

    1. Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of IP and of low potential risk for recurrence
    2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
    3. Adequately treated carcinoma in situ without evidence of disease
  • Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥470 ms calculated from 3 ECGs (within 15 minutes at 5 minutes apart).
  • 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 durvalumab monotherapy.
  • Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
  • Judgment by the investigator that the patient is unsuitable to participate in the study and the patient is unlikely to comply with study procedures, restrictions and requirements.

Sites / Locations

  • Asan Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Durvalumab + Gem/Cis

Gem/Cis

Arm Description

<Investigational arm: preoperative phase (up to 4 cycles)> Durvalumab 1,500 mg IV on Day 1, every 3 weeks (preop period) 1,500 mg IV Day 1, every 4 weeks (postop period) Gemcitabine 1,000 mg IV on Day 1 and 8, every 3 weeks Cisplatin 25 mg IV on Day 1 and 8, every 3 weeks <Postoperative therapy for all patients (up to 6 cycles)> Durvalumab 1,500 mg IV Day 1, every 4 weeks (postop period)

<Control arm: preoperative phase (up to 4 cycles)> Gemcitabine 1,000 mg IV on Day 1 and 8, every 3 weeks Cisplatin 25 mg IV on Day 1 and 8, every 3 weeks <Postoperative therapy for all patients (up to 6 cycles)> Durvalumab 1,500 mg IV Day 1, every 4 weeks (postop period)

Outcomes

Primary Outcome Measures

Ro resection rate
Surgical resection without any residual cancer

Secondary Outcome Measures

Overall survival
Time between the start of study treatment and any cause of death
Event-free survival
Time between the start of study treatment and disease progression or any cause of death
Adverse events
Number of patients experiencing adverse events graded by National Cancer Institute Common Terminology Criteria version 5
Response rate
Graded by Response Evaluation Criteria in Solid Tumors version 1.1

Full Information

First Posted
March 12, 2020
Last Updated
January 30, 2023
Sponsor
Asan Medical Center
Collaborators
Samsung Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT04308174
Brief Title
Neoadjuvant Gemcitabine Plus Cisplatin With or Without Durvalumab in Resectable Biliary Tract Cancer
Acronym
DEBATE
Official Title
Randomized Phase 2 Study of Preoperative Gemcitabine Plus Cisplatin With or Without Durvalumab (MEDI4736) Followed by Postoperative Durvalumab (MEDI4736) in Patients With Localized Biliary Tract Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
May 20, 2020 (Actual)
Primary Completion Date
June 30, 2023 (Anticipated)
Study Completion Date
December 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Asan Medical Center
Collaborators
Samsung Medical Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Considering that the poor prognosis of resected biliary tract cancer and negative impact on the survival outcomes of R1/R2 resection, neoadjuvant chemotherapy may improve R0 resection rates and the survival outcomes of patients with resectable biliary tract cancer. The addition of durvalumab to gemcitabine/cisplatin as neoadjuvant chemotherapy may improve the R0 resection rates compared to gemcitabine/cisplatin in patients with localized biliary tract cancer. In this phase 2 trial, a total of 45 patients with localized biliary tract cancer will be 2:1 randomized to durvalumab plus gemcitabine/cisplatin or gemcitabine/cisplatin.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Biliary Tract Neoplasms, Gallbladder Cancer, Cholangiocarcinoma
Keywords
Biliary tract cancer, Immunotherapy, Neoadjuvant chemotherapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
45 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Durvalumab + Gem/Cis
Arm Type
Experimental
Arm Description
<Investigational arm: preoperative phase (up to 4 cycles)> Durvalumab 1,500 mg IV on Day 1, every 3 weeks (preop period) 1,500 mg IV Day 1, every 4 weeks (postop period) Gemcitabine 1,000 mg IV on Day 1 and 8, every 3 weeks Cisplatin 25 mg IV on Day 1 and 8, every 3 weeks <Postoperative therapy for all patients (up to 6 cycles)> Durvalumab 1,500 mg IV Day 1, every 4 weeks (postop period)
Arm Title
Gem/Cis
Arm Type
Active Comparator
Arm Description
<Control arm: preoperative phase (up to 4 cycles)> Gemcitabine 1,000 mg IV on Day 1 and 8, every 3 weeks Cisplatin 25 mg IV on Day 1 and 8, every 3 weeks <Postoperative therapy for all patients (up to 6 cycles)> Durvalumab 1,500 mg IV Day 1, every 4 weeks (postop period)
Intervention Type
Drug
Intervention Name(s)
Durvalumab + Gem/Cis
Intervention Description
Neoadjuvant Durvalumab + Gemcitabine/Cisplatin
Intervention Type
Drug
Intervention Name(s)
Gem/Cis
Intervention Description
Neoadjuvant Gemcitabine/Cisplatin
Primary Outcome Measure Information:
Title
Ro resection rate
Description
Surgical resection without any residual cancer
Time Frame
4 months
Secondary Outcome Measure Information:
Title
Overall survival
Description
Time between the start of study treatment and any cause of death
Time Frame
1 year
Title
Event-free survival
Description
Time between the start of study treatment and disease progression or any cause of death
Time Frame
1 year
Title
Adverse events
Description
Number of patients experiencing adverse events graded by National Cancer Institute Common Terminology Criteria version 5
Time Frame
13 months
Title
Response rate
Description
Graded by Response Evaluation Criteria in Solid Tumors version 1.1
Time Frame
4 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
19 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Age > 19 years at time of study entry Histologically confirmed adenocarcinoma of biliary tract (intrahepatic, hilar or extrahepatic cholangiocarcinoma, or gallbladder carcinoma). Localized, potentially resectable, non-metastatic disease (determined at the discretion of attending surgeons) based on the results of CT, MRI or PET-CT scans. No active uncontrolled infection, except chronic viral hepatitis under antiviral therapy. Eastern Cooperative Oncology Group (ECOG performance status of 0 or 1 Body weight >30kg Adequate normal organ and marrow function Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up. No other malignant disease apart from non-melanotic skin cancer, carcinoma in situ of the uterine cervix, localized prostate or papillary thyroid cancer, or any other cancer where treated with curative intent > 5 years previously without evidence of relapse Exclusion Criteria: Medical or psychiatric conditions that compromise the patient's ability to give informed consent or to complete the protocol or a history of non-compliance Obstruction of gastrointestinal tract Active gastrointestinal bleeding Myocardial infarction within 6 months prior to the study medication, and other clinically significant heart disease (e.g., unstable angina, congestive heart failure or uncontrolled hypertension) Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the investigator's opinion makes it undesirable for the patient to participate in the study or which would jeopardise compliance with the protocol Combined hepatocellular carcinoma/cholangiocarcinoma is excluded. History of allogenic organ transplantation. History of another primary malignancy except for Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of IP and of low potential risk for recurrence Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease Adequately treated carcinoma in situ without evidence of disease Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥470 ms calculated from 3 ECGs (within 15 minutes at 5 minutes apart). 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 durvalumab monotherapy. Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients. Judgment by the investigator that the patient is unsuitable to participate in the study and the patient is unlikely to comply with study procedures, restrictions and requirements.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Changhoon Yoo, MD, PhD
Organizational Affiliation
Asan Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Asan Medical Center
City
Seoul
ZIP/Postal Code
05505
Country
Korea, Republic of

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
IPD sharing plan will be determined at the time of completion of the study.
Citations:
PubMed Identifier
20375404
Citation
Valle J, Wasan H, Palmer DH, Cunningham D, Anthoney A, Maraveyas A, Madhusudan S, Iveson T, Hughes S, Pereira SP, Roughton M, Bridgewater J; ABC-02 Trial Investigators. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010 Apr 8;362(14):1273-81. doi: 10.1056/NEJMoa0908721.
Results Reference
background
PubMed Identifier
32019287
Citation
Kang J, Jeong JH, Hwang HS, Lee SS, Park DH, Oh DW, Song TJ, Kim KH, Hwang S, Hwang DW, Kim SC, Park JH, Hong SM, Kim KP, Ryoo BY, Yoo C. Efficacy and Safety of Pembrolizumab in Patients with Refractory Advanced Biliary Tract Cancer: Tumor Proportion Score as a Potential Biomarker for Response. Cancer Res Treat. 2020 Apr;52(2):594-603. doi: 10.4143/crt.2019.493. Epub 2019 Dec 18.
Results Reference
background
PubMed Identifier
27664259
Citation
Valle JW, Borbath I, Khan SA, Huguet F, Gruenberger T, Arnold D; ESMO Guidelines Committee. Biliary cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2016 Sep;27(suppl 5):v28-v37. doi: 10.1093/annonc/mdw324. No abstract available.
Results Reference
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Neoadjuvant Gemcitabine Plus Cisplatin With or Without Durvalumab in Resectable Biliary Tract Cancer

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