Study of chemotherapy combined with pembrolizumab in patients with biliary tract cancer

Phase 1

• Conditions: on-resectable or recurrent/metastatic BTC; MedDRA version: 20.0Level: LLTClassification code 10004655Term: Biliary carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: PTClassification code 10004593Term: Bile duct cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: HLTClassification code 10004613Term: Bile duct neoplasms malignantSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: HLGTClassification code 10019815Term: Hepatobiliary neoplasms malignant and unspecifiedSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: SOCClassification code 10029104Term: Neoplasms benign, malignant and unspecified (incl cysts and polyps)System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2017-003323-30-GB
• Lead Sponsor: European Organisation for the Research and Treatment of Cancer (EORTC)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-04-26
• Last Update Posted: 14 December 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

* Histopathological diagnosis of BTC (intra- or extra-hepatic CCA) or GBC
* Non-resectable or recurrent/metastatic BTC
* Availability of archival FFPE (formalin-fixed, paraffin-embedded) tumor tissue for biobanking or possibility to collect tumor biopsy sample at study entry either from primary tumor or any accessible metastatic site
* Possibility to collect blood samples at baseline and during treatment for translational research project
* ECOG performance status 0, 1
* Age = 18 with estimated life expectancy >3 months
* Adequate hematological, liver, renal, cardiac, biliary function:
* Adequate coagulation function
* Patient is not currently participating and receiving study therapy or has not participated in a study of an investigational agent and received study therapy or used an investigation device within 4 weeks prior to enrollment
* Women of child bearing potential (WOCBP) must have a negative serum (or urine) pregnancy test within 72 hours prior to the first dose of study treatment.
* Before patient enrollment, written informed consent must be given according to ICH/GCP, and national/local regulations.
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 50
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

* Patients with ascites grade 2 (moderate) or higher
* Child Pugh B or C hepatic impairment in patients with cirrhosis
* Incomplete recovery from previous surgery or unresolved biliary tract obstruction
* Active infection requiring therapy. Antibiotic treatment should have been completed 5 days before treatmetn start
* Patients who are candidates for curative surgery
* Prior systemic chemotherapy for locally advanced or metastatic disease
* Prior adjuvant chemotherapy is allowed if the last treatment was completed at least 6 months before trial entry and if neither gemcitabine nor cisplatin were given.
* Also, the following treatment modalities are allowed within the rules described below (provided there has been a full recovery):
- Surgery: patients may have undergone a non-curative operation (i.e. R2 resection [with macroscopic residual disease] or palliative bypass surgery only). Patients who have previously undergone curative surgery, must have evidence of non-resectable and measurable disease relapse requiring systemic chemotherapy prior to study entry.
- Radiotherapy: patients may have received prior radiotherapy (with or without radiosensitising low-dose chemotherapy) for localised disease. However, there must be clear evidence of disease progression post-treatment prior to inclusion in this study.
- Photodynamic therapy (PDT) for localized disease only with no evidence of metastatic disease - patients may have received prior PDT, provided the patient has fully recovered and at least 28 days have elapsed since the PDT and there is clear evidence of disease progression at the local site or disease or at a new metastatic site.
- PDT for localised disease to relieve biliary obstruction in the presence of metastatic disease
- Other previous localised treatments targeting intrahepatic lesions such as selective internal radiation therapy (SIRT) , transarterial chemoembolisation (TACE) and radiofrequency ablation are allowed, provided the patient has fully recovered from the treatment before participating in the study
* Active autoimmune disease that has required systemic treatment in past 2 years
* History of (non-infectious) pneumonitis that required steroids or current pneumonitis.
* History of or current interstitial lung disease
* Diagnosis of immunodeficiency, systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment
* Previous allogeneic tissue/solid organ transplant
* Known history of human immunodeficiency virus (HIV), active Hepatitis B or Hepatitis C
* Patients with hyperthyroidism or hypothyroidism unless stable on hormone replacement
* History of another malignancy or a concurrent malignancy. Exceptions include patients who have been disease-free for 5 years, or patients with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible, for example cervical cancer in situ.
* Prior treatment with any anti-CTLA4 monoclonal antibody or anti-PD-1, or PD-L1 or PD-L2 agent.

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective of this single-arm phase II trial is to detect an increase in progression-free survival (PFS) rate at 6 months (according to RECIST version 1.1) in patients with BTC treated with CisGem combined with pembrolizumab as compared to historical controls when treated with standard chemotherapy approach.;Secondary Objective: Secondary objectives are:<br>* Assessing both short term and long term outcome of patients receiving this combined treatment<br>* Establishing the safety of standard chemotherapy combined with pembrolizumab in these patients.<br><br>Important exploratory objectives include:<br>* Evaluation of pathological and clinical predictive factors for response/toxicity<br>* Assessment of immunological responses (cytokines, lymphocyte phenotype, immunoglobulins)<br>* Evaluation of biomarkers for prediction of response and toxicity.;Primary end point(s): PFS rate at 6 months according to RECIST 1.1;Timepoint(s) of evaluation of this end point: At the 6-month assessment.