Intrahepatic Biliary Tract Carcinoma MedDRA version: 20.0 Level: LLT Classification code 10008594 Term: Cholangiocarcinoma non-resectable System Organ Class: 100000004864 MedDRA version: 20.0 Level: LLT Classification code 10073077 Term: Intrahepatic cholangiocarcinoma System Organ Class: 100000004864
Conditions
Interventions
Trade Name: IMFINZI
Product Name: Durvalumab
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: DURVALUMAB
Other descriptive name: Durvalumab
Concentration unit: mg/ml milligram(s)/millil
Sponsors
Institut für Klinische Krebsforschung IKF GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Fully-informed written consent and locally required authorization (European Union [EU]: General Data Privacy Regulation (GDPR)) obtained from the patient prior to performing any protocol-related procedures, including screening evaluations. 2. Age = 18 years. 3. Histologically documented diagnosis of locally-advanced OR limited metasized intrahepatic, BTC not amenable to curative treatment (tumor resection or ablation), specified as • Tumor being confined to the liver or • In case of presence of extrahepatic lesions, metastasis must be stable AND of limited extent* AND patient must have a potential benefit from study participation in comparison to standard of care systemic therapy per local tumor board evaluation. *Limited extent is defined in this protocol as presence of o EITHER =3 malignant extrahepatic lymph nodes (short axis diameter =3cm) o OR metastatic lesions in one organ other than liver (if only single lesion is present diameter MUST be 50% o Any Gastrointestinal deposition that cannot be corrected via angiographic techniques o irreversibly elevated serum bilirubin o renal insufficiency o increased pulmonary shunt fraction being able to deliver > 16.5 mCi to the lungs o gastrointestinal ulceration o hepatic dysfunction o biliary complications o portal hypertension o vascular injury and lymphopenia. 5. Performance status (PS) = 1 (ECOG scale). 6. Body weight >30 kg 7. At least one measurable site of disease as defined by RECIST 1.1 criteria. 8. Adequate bone marrow and renal function including the following: o Hemoglobin = 9.0 g/dL; o absolute neutrophil count = 1.5 x 103/L; o platelets =100x 109 /L; o Creatinine = 1.5 x upper normal limit. o Calculated creatinine clearance =40 mL/min as determined by the Cockcroft-Gault equation 9. Adequate hepatic function (with stenting for any obstruction, if required) including the following: o Serum bilirubin = 1.5 x institutional upper limit of normal (ULN); o AST (SGOT) / ALT (SGPT) = 2.5x institutional ULN (NOTE: if liver metastases are present AST / ALT must be = 5x institutional ULN; o prothrombin time ? 60%; o albumin ? 30 g/L. 10. Female patients with reproductive potential must have a negative urine or serum pregnancy test within 7 days prior to start of trial. 11. Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply: o Women <50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy). o Women =50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more
Exclusion criteria
Exclusion criteria: 1. Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study, or during the follow-up period of an interventional study. 2. Participation in another clinical study with an investigational product within 21 days prior to the first dose of the study treatment. 3. Prior immunotherapy or use of other investigational agents, including prior treatment with an anti-Programmed Death receptor-1 (PD-1), anti-Programmed Death-1 ligand-1 (PD-L1), anti-PD-L2, or anti-cytotoxic T-lymphocyte associated antigen-4 (anti-CTLA-4) antibody, therapeutic cancer vaccines. 4. Presence of peritoneal carcinomatosis or brain metastases. 5. 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 o Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab and tremelimumab may be included only after consultation with the Coordinating Investigator. 6. Any concurrent chemotherapy, investigational product (IP), biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer related conditions (eg, hormone replacement therapy) is acceptable. 7. Prior radiotherapy treatment before the first dose of any study drug. 8. Major surgery (as defined by the Investigator) within 4 weeks prior to enrollment into the study; patients must have recovered from effects of any major surgery. Note: Local non-major surgery for palliative intent (e.g. surgery of isolated lesions, per-cutaneous biliary drainage or biliary stenting) is acceptable. 9. 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], celiac disease, systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis]. The following are exceptions to this criterion: o Patients with vitiligo or alopecia o Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement o Any chronic skin condition that does not require systemic therapy o Patients without active disease in the last 5 years may be included but only after consultation with the study physician 10. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, , serious active, uncontrolled, 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. 11. History of non-infectious pneumonitis requiring steroids, or patients with Grade = 2 pneumonitis. 12. History of another primary malignancy except for: o 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 o Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease o Adequately treated carcinoma in situ without evidence of disease 13. History of leptomeningeal carcinomatosis 14. Brain metastases or spinal cor
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Hypothesis of the trial: the addition of durvalumab +/- tremelimumab to SIRT improves tumor response rate (ORR) in intrahepatic BTC compared to a historical control of SIRT alone. Primary objective To assess the efficacy of durvalumab or durvalumab and tremelimumab administered after standard-of-care SIRT in treatment-naïve patients with unresectable intrahepatic biliary tract cancer as measured by the objective response rate (ORR).;Secondary Objective: Secondary objectives To assess safety of the combined treatment in the two treatment arms. To assess the efficacy of durvalumab or durvalumab and tremelimumab administered after standard-of-care SIRT in treatment-naïve patients with unresectable intrahepatic biliary tract cancer as measured by duration of response (DoR), progression free survival (PFS) and overall survival (OS). Exploratory objectives To assess predictive biomarkers for ORR, DoR, PFS and OS in tumor tissue and blood samples. ;Primary end point(s): Primary Endpoint •Objective response rate (ORR) [according to RECIST 1.1] ;Timepoint(s) of evaluation of this end point: After LPLV, approx. December 2023 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Endpoints • Safety (rate of adverse events) • Duration of response (DoR) • Progression free survival (PFS) • Overall survival (OS) • Exploratory: Predictive biomarkers for ORR, DoR, PFS, OS ;Timepoint(s) of evaluation of this end point: After LPLV, approx. December 2023 | — |
Countries
Germany
Contacts
Public ContactIKF GmbH
Institut für Klinische Krebsforschung IKF GmbH
Outcome results
None listed