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

NCT05239169 | Completed Phase 2

• 2 other identifiers: ADJUBILAIO-HEP-0421/ass
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Biliary Tract Cancer (CCA); Intrahepatic Cholangiocarcinoma; Hilar Cholangiocarcinoma; Distal Cholangiocarcinoma; Gall Bladder Carcinoma

Keywords

Biliary Tract Cancer; CCA

Outcome Measures

Primary Outcomes (1)

• Recurrence free survival at 12 months (RFS@12).

  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.

  12 months

Secondary Outcomes (6)

• Recurrence free survival (RFS)

  30 months

• Overall survival (OS)

  30 months

• Safety: (serious) adverse events

  30 months

• QoL QLQ-C30

  30 months

• QoL BIL21

  30 months

Study Arms (2)

A: Cape+Durva+Treme

EXPERIMENTAL

Capecitabine + Durvalumab + Tremelimumab

Drug: Durvalumab; Drug: Tremelimumab; Drug: Capecitabine

B: Durva+Treme

ACTIVE COMPARATOR

Durvalumab + Tremelimumab

Drug: Durvalumab; Drug: Tremelimumab

Interventions

Durvalumab DRUG

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.

A: Cape+Durva+Treme; B: Durva+Treme

Tremelimumab DRUG

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

A: Cape+Durva+Treme; B: Durva+Treme

Capecitabine DRUG

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

A: Cape+Durva+Treme

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Capable of giving written informed consent, including participation in optional translational research if applicable, and any locally-required authorization (EU Data Privacy Directive in the EU) obtained from the subject prior to performing any protocol-related procedures, including screening evaluations.
• Histologically proven and curatively resected biliary tract cancer (intrahepatic, hilar or distal CCA as well gallbladder carcinoma) without metastatic disease, in the adjuvant situation (R0/R1) up to 16 weeks from surgery.
• Men or women\* ≥ 18 years at time of study entry.
• \*There is no data that indicates a specific gender distribution. Therefore, patients are included regardless of their gender.
• Performance status (PS) ≤ 1 (ECOG scale),with no deterioration over the previous two weeks prior to baseline.
• Must have a life expectancy of at least 12 weeks
• Appropriate hematological, hepatic and renal function:
• Absolute number of neutrophils (ANC) ≥ 1.5 x 109/L
• Platelets ≥ 100 x 109/L
• Hemoglobin ≥ 9 g/dL (5.58 mmol/L)
• Total bilirubin ≤ 1.5 times the upper limit of normal (UNL) or ≤3 x ULN in the presence of documented Gilbert's syndrome (unconjugated hyperbilirubinemia)
• AST (SGOT) and ALT (SGPT) ≤ 2.5 x UNL
• Serum creatinine ≤ 1.5 x UNL or creatinine clearance (measured by 24h urine) ≥ 40 mL / min (i.e., if the serum creatinine level is \> 1.5 x UNL, then a 24-h urine test must be performed to check the creatinine clearance to be determined).
• Adequate coagulability, as determined by the International Normalized Ratio (INR) ≤ 1.5 and partial thromboplastin time (PTT) ≤ 5 seconds above the UNL (unless anti-coagulation therapy has been given). Patients receiving warfarin / phenoprocoumon must be switched to low molecular weight heparin and before starting study-specific procedures.
• Patients of reproductive age must be prepared to use a suitable contraceptive method during the study and up to 3 months after the end of treatment. A suitable method of contraception is defined as surgical sterilization (e.g., bilateral fallopian tube ligation, vasectomy), hormonal contraception (implantable, patch, oral), and double barrier methods (each two-fold combination of intrauterine pessary, condom for men, or women with spermicidal gel, Diaphragm, contraceptive sponge, cervical cap). Women of child-bearing potential must have a negative serum pregnancy test within the last 7 days prior to the start of study therapy.

You may not qualify if:

• Presence of tumors other than biliary tract cancer or a secondary tumor other than squamous or basal cell carcinomas of the skin or in situ carcinomas of the cervix which have been effectively treated. Patients who have received curative treatment for other tumors and have been disease-free for at least 5 years at the time of screening are eligible for enrollment.
• Metastatic biliary tract cancer disease.
• Simultaneous, ongoing systemic immunotherapy, chemotherapy, or hormone therapy not described in the study protocol.
• Simultaneous treatment with a different anti-cancer therapy other than that provided for in the study (excluding palliative radiotherapy only for symptom control)
• Previous therapy with a PD-1, PD-L1 inhibitor (including durvalumab) or CTLA4 inhibitor (including tremelimumab) or classical chemotherapy agents like platinum, fluoropyrimidine or gemcitabine based regimens.
• Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the LKP.
• Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or tremelimumab may be included only after consultation with the LKP.
• Stage B cirrhosis according to Child-Pugh criteria (or worse) or cirrhosis (of any grade) with a history of hepatic encephalopathy or clinically significant ascites resulting from cirrhosis. Clinically significant ascites is defined as ascites resulting from cirrhosis requiring diuretics or paracentesis.
• Known allergic / hypersensitive reactions to at least one of the treatment components.
• Known dihydropyrimidine dehydrogenase (DPD) deficiency.
• Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent within the last 12 months prior to the start of the study.
• Presence of an active, uncontrollable infection.
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.\]). The following are exceptions to this criterion:
• Patients with vitiligo or alopecia
• Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement

Sponsors & Collaborators

• Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest: lead

Study Sites (1)

Krankenhaus Nordwest

Frankfurt am Main, 60488, Germany

Location

MeSH Terms

Conditions

Biliary Tract Neoplasms; Cholangiocarcinoma; Klatskin Tumor; Gallbladder Neoplasms

Interventions

durvalumab; tremelimumab; Capecitabine

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Gallbladder Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Salah Al-Batran, Prof. Dr.

  Institut für Klinische Krebsforschung IKF GmbH

  STUDY DIRECTOR

• Thorsten O. Götze, Prof. Dr.

  Institut für Klinische Krebsforschung IKF GmbH

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Treatment consists of durvalumab and tremelimumab with or without capecitabine.

Study Record Dates

• First Submitted: December 20, 2021
• First Posted: February 14, 2022
• Study Start: May 23, 2022
• Primary Completion: February 20, 2025
• Study Completion: February 20, 2025
• Last Updated: May 1, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)