Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Digestive System Diseases

Rare Diseases

Carcinoma

Cholangiocarcinoma

Klatskin Tumor

Urinary Bladder Neoplasms

Biliary Tract Neoplasms

Adenocarcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Gastrointestinal Neoplasms

Digestive System Neoplasms

Biliary Tract Diseases

Gastrointestinal Diseases

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urinary Bladder Diseases

Urologic Diseases

Male Urogenital Diseases

Bile Duct Cancer

Biliary Tract Cancer

Gallbladder Cancer

Intrahepatic Cholangiocarcinoma

Antineoplastic Agents

All Drugs and Chemicals

Capecitabine

Immunomodulating Agents

Durvalumab

Tremelimumab

Antimetabolites

Antineoplastic Agents, Immunological

Durvalumab at a fixed dose of 1500 mg as an IV infusion over 1 hour, on day 1 together with the Tremelimumab infusion. Durvalumab only infusion to be repeated every 4 weeks for a maximum of 12 months on day 1 of each cycle.

Tremelimumab at a fixed dose of 300 mg as an IV infusion over 1 hour on day 1 of cycle 1.

Capecitabine at 1250 mg/m² p.o. twice a day on days 1 to 14 of a 3-weekly cycle (eight cycles).

Salah Al-Batran, Prof. Dr.

Thorsten O. Götze, Prof. Dr.

This is an interventional, prospective multicenter, open-label, phase II study in patients after curative surgery for BTC in a classic adjuvant situation, consisting of a two arm feasibility pilot part with a randomized pick-the-winner design and an option to proceed into a randomized phase 2/3 trial in order to compare the winner with the current SOC (capecitabine).

The primary objective is to assess the anti-tumor activity of the combination of durvalumab and tremelimumab with or without capecitabine by the recurrence-free survival rate after 12 months (RFS@12).

Secondary objectives are to assess the efficacy by recurrence-free surviaval (RFS) and overall survival (OS); to assess safety of the combination treatments (AEs, impact on liver function, use of subsequent therapies); to assess quality of life (QoL).

Exploratory objective is to perform correlation analysis between selected molecular parameters and clinical data to identify molecular biomarkers predictive for RFS and OS.

Patients will be stratified according to the tumor site (ICC vs. ECC vs. gallbladder) and resection status (R0 vs. R1).

In this pilot trial phase, a pick the winner design is applied to determine wether treatment with durvalumab and tremelimumab in combination with or without capecitabine is more promising.

In the initial pilot phase, 40 patients with histologically proven and curatively resected biliary tract cancer (intrahepatic, hilar or distal CCA as well gallbladder carcinoma) without metastatic disease, will be enrolled in a 1:1 randomized design (i.e. 20 patients per Arm).

Patients will be recruited from up to 15 sites and patients withdrawn from the trial will not be replaced.

Treatment consists of durvalumab and tremelimumab with or without capecitabine.

Immunotherapy With Durva and Treme With or Without Capecitabine in Adjuvant Treatment for Biliary Tract Cancer

A Phase II Study of Immunotherapy With Durvalumab and Tremelimumab in Combination With Capecitabine or Without Capecitabine in Adjuvant Situation for Biliary Tract Cancer

Recurrence free survival at 12 months (RFS@12) will be defined as the proportion of allocated subjects without any recurrence/progression and alive at 12 months after the date of treatment allocation.

Recurrence-free survival (RFS) will be determined as time from the date of treatment allocation to the date of (1) any recurrence/progression (local or regional \[including invasive ipsilateral tumor and invasive locoregional tumor\], or distant) or (2) death due to any cause.

Overall survival (OS) will be determined as time from the date of treatment allocation to the date of death due to any cause. A subject who has not died will be censored at last known date alive.

Safety assessments will include adverse events. All observed toxicities and side effects will be graded according to NCI CTCAE v5.0 for all patients and the degree of association of each with the study treatment assessed and summarized. Treatment related serious adverse events rate (SAE) will be determined.

QoL will be assessed by the EORTC QLQ-C30 questionnaire in itsmost current version.

The QoL analyses will include QoL mean values, QoL response and time to symptom deterioration (TTSD) defined as the time interval between randomization and the first decrease by ≥ 10-points. All randomly assigned patients with a baseline and at least one post-baseline assessment will be included in TTSD analyses. Patients without observed deterioration will be censored at the time of their last QoL assessment.

EORTC QLQ C30 (30 questions) regarding body fitness, daily routines, restrictions at work and hobby, appetite, fatigue, cough, breathlessness, pain, tiredness, body conditions, state of health and Quality of life.

QoL will be assessed by the EORTC QLQ-BIL21 questionnaire in its most current version.

The QoL analyses will include QoL mean values, QoL response and time to symptom deterioration (TTSD) defined as the time interval between randomization and the first decrease by ≥ 10-points. All randomly assigned patients with a baseline and at least one post-baseline assessment will be included in TTSD analyses. Patients without observed deterioration will be censored at the time of their last QoL assessment.

EORTC QLQ BIL21 (21 questions) regarding eating habits, body fitness, fatigue, pain, tiredness and mental health.

QoL will be assessed by the QoL EQ-5D-5L questionnaire in its most current version.

The QoL analyses will include QoL mean values, QoL response and time to symptom deterioration (TTSD) defined as the time interval between randomization and the first decrease by ≥ 10-points. All randomly assigned patients with a baseline and at least one post-baseline assessment will be included in TTSD analyses. Patients without observed deterioration will be censored at the time of their last QoL assessment.

EQ 5D-5L (6 questions) about mobility, sorrows, daily routine, pain, anxiety and health perception.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Immunotherapy With Durva and Treme With or Without Capecitabine in Adjuvant Treatment for Biliary Tract Cancer	NCT05239169	Biliary Tract C... Intrahepatic Ch... Hilar Cholangio... Distal Cholangi... Gall Bladder Ca...	Durvalumab Tremelimumab Capecitabine	18 Years -	Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
Immunotherapy With Durva and Treme With or Without Capecitabine in Adjuvant Treatment for Biliary Tract Cancer	NCT05239169	Biliary Tract C... Intrahepatic Ch... Hilar Cholangio... Distal Cholangi... Gall Bladder Ca...	Durvalumab Tremelimumab Capecitabine	18 Years -	Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
Immunotherapy With Durva and Treme With or Without Capecitabine in Adjuvant Treatment for Biliary Tract Cancer	NCT05239169	Biliary Tract C... Intrahepatic Ch... Hilar Cholangio... Distal Cholangi... Gall Bladder Ca...	Durvalumab Tremelimumab Capecitabine	18 Years -	Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest

Spots Global Cancer Trial Database for biliary tract cancer (cca)