Biliary Tract Cancer
Conditions
Brief summary
This is a single-arm, phase I/II trial in biliary tract cancer (BTC) patients. The purpose of this trial is to evaluate the safety and effect of PD-1 inhibitor in combination with gemcitabine/cisplatin chemotherapy in patients with advanced unresectable or metastatic BTCs. The primary objective: 6-month progression free survival (PFS). The second objectives: objective clinical response(according to RECIST version 1.1), safety, symptom control and quality of life (QoL) (according to EORTC QoL C30 and BIL 21), overall survival. The exploratory objectives: assessment of immunological response (cytokines, lymphocyte phenotype, immunoglobulins), and evaluation of pathological, immunological and clinical predictive factors for response/toxicity.
Interventions
DRUGPD-1 inhibitor + Gemcitabine + Cisplatin
Gemcitabine: 1000mg/m2 on day 1 and 5 every 3 weeks. Cisplatin: 75mg/m2 on day 1 every 3 weeks. PD-1 inhibitor: Nivolumab 3mg/kg, or SHR-1210 200mg.
Sponsors
Chinese PLA General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Enrolled patients will be treated with PD-1 inhibitor in combination with gemcitabine/cisplatin chemotherapy.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Age≥18 years with estimated life expectancy \>3 months. * Histopathological/cytological diagnosis of unresectable or recurrent / metastatic biliary tract carcinoma (intra-hepatic, extrahepatic or gall bladder) and had at least one measurable disease (≥1cm) by CT or MRI. * Patients should provide samples of tumor tissue biopsied or resected no more than 3 months before enrollment and be willing to accept biopsy in the process of the study. * Patients may have received prior radiotherapy,chemotherapy,or other local ablative therapies, which completed ≥ 4 weeks prior to registration AND patient has recovered to \<= grade 1 toxicity. * ECOG (Eastern Cooperative Oncology Group) performance status of 0-2. * Adequate organ and marrow function obtained ≤ 2 weeks prior to registration as defined below: leukocytes greater than or equal to 3.0 x 10\^9/L absolute neutrophil count greater than or equal to 1.0 x 10\^9/L platelets greater than or equal to 100 x 10\^9/L hemoglobin greater than or equal to 90 g/L total bilirubin less than or equal to 2 xULN serum albumin should be no less than 25g/L ALT or AST less than 2 xULN serum creatinine less than 1.5 x ULN * Ability to understand and willingness to sign a written informed consent document. * women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, and up to 120 days after the last dose of the drug.
Exclusion criteria
* Active, known or suspected autoimmune diseases. * Known brain metastases or active central nervous system (CNS). If patients with CNS metastases were treated with radiotherapy for at least 3 months prior to enrollment and have no central nervous symptoms and are off corticosteroids, they will be eligible but will need a Brain MRI prior to enrollment. * Participants are being treated with either corticosteroids (\>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of enrollment. * Prior therapy with anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibody (including ipilimumab or any other antibody specifically targeting T-cell costimulation or checkpoint pathways). * History of severe hypersensitive reactions to other monoclonal antibodies. * History of allergy or intolerance to study drug components. * Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results. * History or concurrent condition of interstitial lung disease of any grade or severely impaired pulmonary function. * Uncontrolled intercurrent illness including ongoing or active systemic infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia (excluding insignificant sinus bradycardia and sinus tachycardia) or psychiatric illness/social situations and any other illness that would limit compliance with study requirements and jeopardize the safety of the patient. * History of human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS). * Pregnant or breast-feeding patients. Women of childbearing potential must have a pregnancy test performed within 7 days before the enrollment, and a negative result must be documented. * Previous or concurrent cancer within 3 years prior to treatment start EXCEPT for curatively treated cervical cancer in situ, non-melanoma skin cancer, superficial bladder tumors \[Ta (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor invades lamina propria)\]. * Vaccination within 30 days of study enrollment. * Active bleeding or known hemorrhagic tendency. * Patients with unhealed surgical wounds for more than 30 days. * Being participating any other trials or withdraw within 4 weeks.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The percentage of patients alive and without progression at 6 months | 6 months | The primary objective of this trial is the progression free survival (PFS) at 6 months in patients with advanced unresectable or metastatic BTCs treated with PD-1 inhibitor in combination with gemcitabine plus cisplatin. Progression will be defined clinically or on imaging as per immune related response evaluation criteria in solid tumors (irRECIST) definition |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The percentage of patients that respond to combination treatment | Enrolled patients will be followed until death, withdrawal from study, or until 2 years. | Overall response rate is defined as the sum of partial responses and complete responses. Partial and complete response will be defined as per irRECIST criteria. |
| Median overall survival time | Patients will be followed until death, withdrawal from study, or until 2 years. | The median overall survival (OS) time is defined as the time from enrollment to death. |
| List of adverse event frequency and grade | Up to 120 days after last administration of PD-1 inhibitor | To evaluate the safety of PD-1 inhibitor in combination with standard chemotherapy in patients with advanced BTCs according to CTCAE 4.0. |
Countries
China
Contacts
Primary ContactWeidong Han, Ph.D
Backup ContactKaichao Feng, MD
Outcome results
None listed