Biliary tract cancer
Conditions
Interventions
First-line treatment cohort:Donafenib tablet, 200 mg BID Po
Toripalimab, 240 mg Q3W IV
Sponsors
Peking Union Medical College Hospital, Chinese Academy of Medical Sciences
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Aged over 18 years; 2. Patients with unresectable advanced biliary tract cancer confirmed by histology or pathology, including gallbladder cancer, intrahepatic cholangiocarcinoma and extrahepatic cholangiocarcinoma; 3. (1) Patients without systemic treatment and who refuse to use standard chemotherapy regimens recommended in CSCO guidelines and NCCN guidelines for first-line systemic treatment (included in the first-line treatment cohort); (2) Patients who failed or were intolerant of first-line systemic therapy (included in the second-line treatment cohort); 4. At least one measurable lesion (according to RECIST v1.1) (definition of measurable lesions: non-lymphoid lesions with the longest single diameter >= 10 mm, or lymph node lesions with a short diameter >= 15 mm; lesions after previous interventional, radiotherapy or ablation therapy that have clearly progressed according to RECIST1.1 criteria and whose longest diameter is >=10 mm can also be used as measurable target lesions. ); 5. The time from the previous treatment to the first study drug administration: surgical treatment, interventional treatment, radiotherapy, and the last drug treatment including the end of chemotherapy > 4 weeks; 6. Child-Pugh score of liver function = 50%; 8. ECOG 0-1 points; 9. Expected survival period >= 12 weeks; 10. Laboratory test values within 14 days before treatment must meet the following criteria: (1) Routine blood examination: Hb>=90 g/L; ANC>=1.5x10^9/L; PLT>=75x10^9/L; (2) Biochemical tests: ALB >=28 g/L; ALT and AST = 50 mL/min (creatinine clearance needs to be calculated by the Cockcroft-Gault formula); (4) Coagulation function: when the international standard ratio (INR) or prothrombin time (PT) is less than or equal to 1.5 prothrombin; when the activated partial coagulation time (APTT) is less than or equal to 1.5T; 11. Those who voluntarily signed a written informed consent, and can understand and comply with the trial protocol, taking medication and follow-up; 12. Agree to provide previously stored tumor tissue specimens and related pathology reports, or agree to accept tumor tissue biopsy (According to the evaluation of the investigator, when the patient agrees and it is convenient to obtain tumor tissue samples, it is recommended that patients with typical space-occupying lesions and clinical diagnosis should collect a new coarse needle biopsy tissue of bile duct tumor lesions during the screening period). The site where the biopsy tissue is required to be obtained, has not received local therapy such as radiotherapy before, and the patient cannot receive systemic antitumor therapy during the period from the biopsy sampling to the first study drug.
Exclusion criteria
Exclusion criteria: 1. The pathological diagnosis is hepatocellular carcinoma, mixed liver cancer and other malignant tumor components other than biliary tract cancer; 2. Known hematological malignancies, malignant primary brain tumors or malignant sarcomas, other malignant primary solid tumors within 5 years, unless the patient has received potentially curative treatment and there is no evidence of the disease within 5 years. Note: This time requirement (i.e., within 5 years) does not apply to patients with basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, cervical carcinoma in situ, or other carcinoma in situ who have successfully undergone surgical resection; 3. Active or untreated central nervous system (CNS) metastases detected by computed tomography (CT) or magnetic resonance imaging (MRI) during the screening period and before imaging evaluation; 4. Those with portal hypertension and a high risk of bleeding according to the investigator's opinion; or those with red signs during gastroscopy; 5. Suffering from any active autoimmune disease or history of autoimmune disease (such as autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism or hypothyroidism, asthma requiring bronchodilator treatment, etc.); patients with vitiligo or complete remission of asthma in childhood without any intervention in adulthood can be included; 6. Patients with active upper gastrointestinal ulcers, significant vomiting, chronic diarrhea, intestinal obstruction, malabsorption or other diseases known to affect drug absorption, distribution, metabolism or clearance; patients with uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage (once a month or more frequently); 7. The patient is known or suspected to have a history of allergy to Donafenib or similar drugs, or a history of hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins, or allergic to the excipients of the study drug; 8. Patients who have received allogeneic stem cell or solid organ transplantation in the past; 9. Previous treatment with Donafenib; 10. Have received any live vaccine within 4 weeks before enrollment; 11. Not fully recovered from the previous surgery, and have performed medium and large surgical operations within 4 weeks before the first study administration; 12. Patients who have taken Chinese patent medicines or modern Chinese medicine preparations with anti-biliary tract cancer indications within 2 weeks before the first study drug administration; 13. There are any significant clinical or laboratory abnormalities that the investigator considers to affect the safety evaluation, such as: uncontrolled diabetes, hypertension, and those who cannot be reduced to the following range after monotherapy (systolic blood pressure 10 mg/day prednisone or other equivalent hormones), and continued use w
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression-free survival; | — |
Secondary
| Measure | Time frame |
|---|---|
| Disease control rate;Objective response rate;Duration of relief;Survival rate;ECOG score;Tumor marker;Adverse event;Serious adverse event; | — |
Countries
China
Contacts
Public ContactZhao Haitao
Peking Union Medical College Hospital, Chinese Academy of Medical Sciences
Outcome results
None listed