A Phase II, Multicenter, Randomized Study of Durvalumab and Lenvatinib With or Without Chemotherapy in First-Line Treatment of Advanced Biliary Tract Cancer
A Phase II, Multicenter, Randomized Study of Durvalumab and Lenvatinib With or Without Chemotherapy in First-Line Treatment of Advanced Biliary Tract Cancer
Explore the impact of the first-line application of Durvalumab combined with Lenvatinib, with or without chemotherapy, on the survival, disease progression, and drug safety of patients with advanced biliary tract cancers.
This trial is a two-arm, randomized, multi-center phase II clinical study. Eligible subjects who meet the study criteria will be screened and randomized in a 1:1 ratio to receive treatment with intravenous infusion of Durvalumab combined with oral lenvatinib, with or without chemotherapy. The investigators will closely follow up and assess the efficacy and safety of the combined treatment, evaluate the progression-free survival of the subjects until progression occurs, and observe their overall survival as a secondary outcome.
Inclusion Criteria:
Serum bilirubin ≤2.0×ULN; these conditions do not apply to patients with confirmed Gilbert's syndrome. Any clinically significant biliary obstruction should be resolved before randomization.
Appropriate renal function: creatinine ≤1.5×ULN, or creatinine clearance rate (CCr) >50mL/min (using the standard Cockcroft-Gault formula):
Female: CrCl = ((140 - age) x weight (kg) x 0.85) / 72 x serum creatinine (mg/dL) Male: CrCl = ((140 - age) x weight (kg) x 1.00) / 72 x serum creatinine (mg/dL)
●Women of childbearing potential: agree to abstain from sexual intercourse or use contraceptive methods with a failure rate of less than 1% during the treatment period and for at least 6 months after the last dose.
If a female patient has menstruation and has not reached menopause (continuous absence of menstruation for ≥12 months without other reasons), and has not undergone sterilization surgery (removal of ovaries and/or uterus), she is considered to be of childbearing potential.
Examples of contraceptive methods with a failure rate of less than 1% include bilateral tubal ligation, male sterilization, hormone-based contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.
The reliability of sexual restraint 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 day, ovulation period, symptom temperature, or post-ovulation method) and ejaculation outside the vagina are unacceptable contraceptive methods.
●Male: agree to abstain from sexual intercourse or use contraceptive measures, agree not to donate sperm, as defined below: When the female partner is of childbearing potential, male patients must abstain during the treatment period and for 6 months after the last dose, or use a condom plus other contraceptive methods to achieve a failure rate of less than 1%. Male patients must also agree not to donate sperm during the same period. When the female partner is already pregnant, male patients must abstain or use a condom to prevent fetal exposure to the study during the treatment period and for 6 months after the last dose.
The reliability of sexual restraint 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 day, ovulation period, symptom temperature, or post-ovulation method) and ejaculation outside the vagina are unacceptable contraceptive methods.
Exclusion Criteria:
Multiple factors affecting oral administration of lenvatinib (such as inability to swallow, chronic diarrhea and intestinal obstruction, or other conditions that significantly affect drug intake and absorption).
Hepatic or renal dysfunction, with manifestations such as jaundice, ascites, and/or bilirubin >3×ULN, creatinine ratio >3.5g/24 hours, or renal failure requiring blood or peritoneal dialysis, and/or urinary routine showing urine protein ≥++ or confirmed 24-hour urine protein quantification >1.0g.
Active autoimmune disease or history of autoimmune disease within the past 2 years; participants with active, known, or suspected autoimmune diseases that may affect important organ function or require systemic immunosuppressive therapy are excluded, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, antiphospholipid syndrome associated with thrombosis, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. However, participants with 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 relapse without external triggering factors are allowed. Replacement therapy (such as thyroid hormone, insulin, or physiological corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
●Known active central nervous system (CNS) metastasis and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate as long as they are stable (evidence of no progression on imaging at least 4 weeks before the first trial treatment and any neurological symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and have not used steroids for at least 7 days before trial treatment. This exception does not include carcinomatous meningitis, which is excluded regardless of clinical stability. Participants with known or untreated brain metastases or epilepsy requiring medication are also excluded.
Planned or prior organ or allogeneic bone marrow transplantation. Known history of active tuberculosis (Mycobacterium tuberculosis). History of gastrointestinal bleeding within the past 6 months or clear evidence of gastrointestinal bleeding tendencies, such as bleeding esophageal varices, locally active gastrointestinal ulcerative lesions, fecal occult blood ≥(++), cannot be included; if fecal occult blood (+), gastroscopy is required; evidence or history of bleeding mechanism disorders of grade ≥3 (CTCAE 5.0), or other bleeding disorders.