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

Sponsor

Asan Medical Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT04308174

Collaborator

Samsung Medical Center (Other)

Enrollment

Location

Arms

43.3

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Biliary Tract Neoplasms Gallbladder Cancer Cholangiocarcinoma	Drug: Durvalumab + Gem/Cis Drug: Gem/Cis	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

45 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

May 20, 2020

Anticipated Primary Completion Date :

Sep 30, 2022

Anticipated Study Completion Date :

Dec 30, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Durvalumab + Gem/Cis <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)	Drug: Durvalumab + Gem/Cis Neoadjuvant Durvalumab + Gemcitabine/Cisplatin
Active Comparator: Gem/Cis <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)	Drug: Gem/Cis Neoadjuvant Gemcitabine/Cisplatin

Arm

Intervention/Treatment

Experimental: Durvalumab + Gem/Cis

<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)

Drug: Durvalumab + Gem/Cis

Neoadjuvant Durvalumab + Gemcitabine/Cisplatin

Active Comparator: Gem/Cis

<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)

Drug: Gem/Cis

Neoadjuvant Gemcitabine/Cisplatin

Outcome Measures

Primary Outcome Measures

Ro resection rate [4 months]
Surgical resection without any residual cancer

Secondary Outcome Measures

Overall survival [1 year]
Time between the start of study treatment and any cause of death
Event-free survival [1 year]
Time between the start of study treatment and disease progression or any cause of death
Adverse events [13 months]
Number of patients experiencing adverse events graded by National Cancer Institute Common Terminology Criteria version 5
Response rate [4 months]
Graded by Response Evaluation Criteria in Solid Tumors version 1.1

Eligibility Criteria

Criteria

Ages Eligible for Study:

19 Years and Older

Sexes Eligible for Study:

All

Accepts 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

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.