A Phase II study of immunotherapy with durvalumab and tremelimumab in combination with capecitabine or without capecitabine in adjuvant situation for biliary tract cancer

Phase 1

• Conditions: biliary tract cancer; MedDRA version: 27.0Level: PTClassification code 10008593Term: CholangiocarcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: HLTClassification code 10004675Term: Biliary tract and gallbladder therapeutic proceduresSystem Organ Class: 10042613 - Surgical and medical procedures; MedDRA version: 20.0Level: PTClassification code 10048798Term: Biliary adenomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: PTClassification code 10061696Term: Biliary tract operationSystem Organ Class: 10042613 - Surgical and medical procedures; MedDRA version: 27.0Level: LLTClassification code 10073077Term: Intrahepatic cholangiocarcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 27.0Level: LLTClassification code 10074878Term: Hilar cholangiocarcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: LLTClassification code 10017620Term: Gallbladder carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2021-002389-41-DE
• Lead Sponsor: Frankfurter Institut für Klinische Krebsforschung IKF GmbH am Krankenhaus Nordwest

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2022-02-17
• Last Update Posted: 15 April 2024

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

1.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.
2.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.
3.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.
4.Performance status (PS) = 1 (ECOG scale),with no deterioration over the previous two weeks prior to baseline.
5.Must have a life expectancy of at least 12 weeks
6.Appropriate hematological, hepatic and renal function [...]
7.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.
8.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. [...]Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year. Men receiving IMP and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 7 months after the last dose of investigational products (durvalumab and tremelimumab). [...]
9.Subject is willing and able to comply with the protocol (including contraceptive measures) for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 38
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 2

Exclusion Criteria

1.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.
2.Metastatic biliary tract cancer disease.
3.Simultaneous, ongoing systemic immunotherapy, chemotherapy, or hormone therapy not described in the study protocol.
4.Simultaneous treatment with a different anti-cancer therapy other than that provided for in the study
5.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.
6.Any unresolved toxicity NCI CTCAE Grade =2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria
•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.
7.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.
8.Known allergic / hypersensitive reactions to at least one of the treatment components.
9.Known dihydropyrimidine dehydrogenase (DPD) deficiency.
10.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.
11.Presence of an active, uncontrollable infection.
12.Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease. [...] The following are exceptions to this criterion: Patients with vitiligo or alopecia, Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement,
Any chronic skin condition that does not require systemic therapy, Patients without active disease in the last 5 years may be included but only after consultation with the study physician, Patients with celiac disease controlled by diet alone
[...]
21.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 or180 days after the last dose of durvalumab + tremelimumab combination therapy.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified