A Phase II Study of Adjuvant Durvalumab Combined With GEMOX/GC Chemotherapy Followed by Lenvatinib Versus Capecitabine in Biliary Tract Cancer.

A Randomized, Open-label, Phase II Clinical Study of Durvalumab Combined With GEMOX/GC Chemotherapy Followed by Lenvatinib Versus Capecitabine as Adjuvant Therapy for Biliary Tract Cancer.

This study is designed as a prospective, randomized, open-label, phase II clinical trial to systematically evaluate the efficacy and safety of durvalumab combined with GEMOX/GC chemotherapy followed by lenvatinib, compared with capecitabine monotherapy, as adjuvant therapy for biliary tract cancer (BTC) after curative-intent resection.The primary objective is to determine whether the combination regimen can significantly improve the 1-year recurrence-free survival (RFS) rate. Secondary objectives include assessment of overall survival (OS) and the incidence of treatment-related adverse events. The overall aim is to identify a more effective and safer treatment strategy for postoperative adjuvant therapy in BTC.

Inclusion Criteria:

1. The subjects voluntarily participated in the study and agreed to sign the written informed consent. They had good compliance and cooperated with the follow-up.
2. When signing the informed consent form, one must be at least 18 years old and no older than 75 years old, and there is no restriction on gender.
3. Histologically confirmed cholangiocarcinoma or gallbladder cancer (excluding pancreatic cancer or ampullary cancer)
4. Having undergone radical surgical treatment (R0 or R1 resection)
5. The ECOG score is between 0 and 1
6. The hematology and organ functions are adequate. Based on the following laboratory test results obtained within 14 days prior to the start of the treatment (unless otherwise specified)
7. Blood routine test: (Within 14 days before screening, no blood transfusion, no use of G-CSF, and no use of drugs for correction) Hb ≥ 90 g/L; Neutrophils ≥ 1.5 × 10^9/L; PLT ≥100×10^9/L
8. Biochemical test: (No albumin transfusion within 14 days)
9. Appropriate liver function: ALT and AST ≤ 2.5 × ULN; serum bilirubin ≤ 2.0 × normal upper limit (ULN); these conditions do not apply to patients with confirmed Gilbert syndrome. Any clinically significant biliary obstruction should be relieved before enrollment. Albumin ≥ 2.8 g/dL. Appropriate renal function: creatinine ≤ 1.5 × ULN, or creatinine clearance rate (CCr) > 50 mL/min (calculated using the standard Cockcroft-Gault formula)
10. Coagulation function: International Normalized Ratio (INR) ≤ 1.5
11. Fertile women: Agree to abstain from sexual intercourse (avoiding heterosexual intercourse) or use a contraceptive method with a failure rate of less than 1% during the treatment period and for at least 6 months after the last administration. If the female patient has menstruated, has not reached post-menopausal status (continuous absence of menstruation for ≥ 12 months, no other causes found apart from menopause), and has not undergone sterilization surgery (removal of ovaries and/or uterus), then it is considered that the patient is fertile. Examples of contraceptive methods with a failure rate of less than 1% include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormonal release intrauterine devices, and copper intrauterine devices. The reliability of sexual abstinence should be evaluated relative to the duration of the clinical trial and the patient's preferred lifestyle and daily routine. Periodic abstinence (such as calendar days, ovulation period, symptom-based body temperature, or post-ovulation methods) and withdrawal from sexual intercourse are unacceptable contraceptive methods.
12. Male: Agree to abstinence (not engaging in heterosexual sexual intercourse) or use of contraceptive measures, agree not to donate sperm, defined as follows: When the female partner has reproductive capacity, the male patient must abstain from sexual activity during the treatment period and for 6 months after the last administration, or use condoms and other contraceptive methods to ensure a contraceptive failure rate of less than 1% per year. During the same period, the male patient must also agree not to donate sperm. When the female partner is pregnant, the male patient must abstain from sexual activity or use condoms for contraception during the treatment period and for 6 months after the last administration, to avoid any impact on the fetus. The reliability of sexual abstinence should be evaluated relative to the duration of the clinical trial and the patient's preferred lifestyle and daily routine. Periodic abstinence (such as calendar days, ovulation period, symptom-based body temperature or after ovulation methods) and withdrawal from sexual intercourse are unacceptable contraceptive methods.

Exclusion Criteria:

1. Pancreatic cancer or ampullary cancer
2. Not yet fully recovered from the surgery or with unremoved bile duct obstruction
3. Pregnant women (with a positive pregnancy test before taking the medicine) or lactating women
4. Having had other untreated malignant tumors in the past (within the last 5 years) or simultaneously, excluding cured skin basal cell carcinoma, skin squamous cell carcinoma, in situ breast cancer and in situ cervical cancer, treated superficial bladder cancer, and prostate adenocarcinoma that underwent surgical treatment and whose PSA tumor marker was within the normal range.
5. Who has previously received immunotherapy or chemotherapy
6. Serious coexisting diseases that may interfere with the treatment of the proposed plan, including potential severe infections
7. There is drug abuse; or any medical, psychological or social condition that may affect the research, the patient's compliance, be unstable, or even potentially endanger the patient's safety.
8. Significant clinical cardiovascular and cerebrovascular diseases, including but not limited to acute myocardial infarction occurring within 6 months prior to enrollment, severe/unstable angina pectoris, cerebrovascular accident or transient cerebral ischemic attack, congestive heart failure (NYHA classification ≥ 2 grade); arrhythmias requiring anti-arrhythmic drugs (except beta-blockers or digoxin); repeated electrocardiogram QTc interval > 480 milliseconds (ms)
9. Presence of persistent infection of grade 2 or above (CTCAE 5.0)
10. Having a history of thromboembolic events within the past 6 months (including stroke and/or transient ischemic attack)
11. Hypertension that has not been well controlled by antihypertensive drugs (systolic blood pressure > 160 mmHg, diastolic blood pressure > 100 mmHg)
12. Participants who had active autoimmune diseases or autoimmune disease history in the past two years; those with active, known, or suspected autoimmune diseases that may affect important organ functions or that may require systemic immunosuppressive therapy, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, antiphospholipid syndrome related to vascular thrombosis, Wegener's granulomatosis, Sjogren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis or glomerulonephritis. However, type 1 diabetes, hypothyroidism requiring only hormone replacement, skin diseases that do not require systemic treatment (such as vitiligo, psoriasis or alopecia) or participants who will not have a recurrence without external triggering factors are allowed. Alternative therapies (such as thyroid hormone, insulin or physiological corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) are not considered as a form of systemic treatment.
13. A known history of active tuberculosis (with the tuberculosis bacteria)
14. Those who have a history of gastrointestinal bleeding within the past 6 months or have a clear tendency towards gastrointestinal bleeding, such as esophageal varices with bleeding risk, active gastrointestinal ulcer lesions, or fecal occult blood ≥ (++), are not eligible for enrollment; those with evidence or history of ≥ 3 grade (CTCAE 5.0) bleeding events due to bleeding mechanism disorders are also excluded.
15. Severe non-healing wounds, ulcers or fractures
16. There are unresolved toxicities of grade > 1 that were caused by any previous treatment/operation (CTCAE 5.0, except for hair loss, anemia, and hypothyroidism)
17. Patients who have objective evidence of severe lung function impairment in the past and at present, such as a history of severe pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonia, or drug-related pneumonia
18. After the researchers' comprehensive assessment of the patient's condition, it was determined that the patient was not suitable for participating in this study.
19. At the same time, he/she was also involved in another clinical study.