Patients with unresectable gallbladder carcinoma or intrahepatic and extrahepatic cholangiocarcinoma confirmed by histopathology
Conditions
Interventions
Treatment group:Anlotinib combined with Bemotamab and Albumin-bound Paclitaxel
Anlotinib, 10 mg once daily, orally, for 2 consecutive weeks followed by a 1-week rest period.
Bemotamab, 1200 mg is adm
Sponsors
Hunan Provincial People's Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1.Age: 18 to 75 years old; both male and female subjects are eligible. 2.Patients with histopathologically confirmed unresectable gallbladder carcinoma or intrahepatic and extrahepatic cholangiocarcinoma. 3.Subjects whose immediate prior line of therapy was standard regimen containing immune checkpoint inhibitors (either PD-1 or PD-L1 inhibitors). Disease progression or intolerance to ICIs assessed per RECIST v1.1 criteria (discontinuation of ICIs due to grade =2 adverse events (AEs), and resumption of ICIs is feasible after symptomatic supportive treatment). The interval from the last administration of any immune checkpoint inhibitor must be more than 2 weeks. For prior ICI therapy, subjects must have achieved at least one complete response (CR)/partial response (PR), or stable disease (SD) lasting for a minimum of 6 weeks. Subjects with failed prior adjuvant therapy are permitted to enroll. 4.At least one measurable lesion as defined by RECIST version 1.1. 5.Eastern Cooperative Oncology Group (ECOG) performance status: 0 or 1. 6.Estimated overall survival >= 12 weeks. 7.Adequate function of major organs, meeting the following laboratory criteria: (1) Hematology: 1). Hemoglobin (HB) >= 90 g/L (no blood transfusion within the preceding 14 days); 2). Absolute neutrophil count (ANC) >= 1.5×10?/L; 3). Platelet count (PLT) >= 80×10?/L. (2) Serum biochemistry: 1). Albumin (ALB) >= 30 g/L (no albumin transfusion within the preceding 14 days); 2). Alanine transaminase (ALT) and aspartate transaminase (AST) = 60 mL/min. 8.Left ventricular ejection fraction (LVEF) >= the lower limit of normal (50%) as assessed by Doppler echocardiography. 9.Subjects voluntarily participate in this trial, sign written informed consent, and are able to comply with all protocol-specified study visits and procedures. 10.Female subjects of childbearing potential, and male subjects whose sexual partners are women of childbearing potential, must use effective contraception throughout the treatment period and for 6 months after the end of treatment.
Exclusion criteria
Exclusion criteria: 1. Patients previously treated with anlotinib hydrochloride or bemotuzumab are excluded. 2. Patients who received local therapies (including but not limited to TACE, HAIC, ablation, radiotherapy) less than 1 month prior to enrollment. 3. Patients who received anti-tumor traditional Chinese medicine less than 2 weeks before enrollment. Relevant herbal ingredients include brucea javanica fruit, coix seed, lentinan, blister beetle, toad skin, astragalus, sophora flavescens, marsdenia tenacissima, chebula, icaritin, etc. 4. Patients meeting any of the following conditions within 28 days before enrollment: (1) Undergoing major surgery, incisional biopsy or significant traumatic injury; (2) Experiencing any grade >= 3 hemorrhagic events per CTCAE v5.0, or having unhealed wounds, ulcers or fractures; (3) Participating in other clinical trials of anti-tumor agents. 5. Patients with unresolved toxicities > grade 1 (per NCI-CTCAE v5.0) from prior therapies (alopecia excluded). Patients with prior immune-related adverse events (irAEs) requiring permanent discontinuation of ICIs are excluded, including: severe/life-threatening bullous diseases (G3–4), moderate/life-threatening gastrointestinal toxicities, severe/life-threatening hepatitis (G4), pancreatitis (G3–4), pneumonitis (G3–4), severe proteinuria (G3–4), severe uveitis/episcleritis (G3–4), myasthenia gravis (G3–4), any-grade Guillain-Barré syndrome or transverse myelitis, encephalitis (G2–4), myocarditis (G2–4), severe inflammatory arthritis markedly impairing daily activities and quality of life. For other irAEs that recover to = 150 mmHg or diastolic BP >= 100 mmHg on single antihypertensive agent; or requiring >= 2 antihypertensives); history of hypertensive crisis or hypertensive encephalopathy. (2) Grade >= 1 myocardial ischemia, myocardial infarction, arrhythmia (QTc >450 ms in males, >470 ms in females), NYHA grade >= 2 congestive heart failure, severe/unstable angina, or prior coronary/peripheral artery bypass grafting. (3) Active tuberculosis. (4) Renal failure requiring hemodialysis or peritoneal dialysis. (5) Poorly controlled diabetes with fasting blood glucose >10 mmol/L. (6) Urinalysis showing proteinuria =2+ confirmed by 24-hour urinary protein >1.0 g. (7) Coagulopathy (INR >1.5, PT > ULN +4 s, or APTT >1.5 × ULN) with bleeding diathesis or receiving thrombolytic/anti
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective Response Rate (ORR); | — |
Secondary
| Measure | Time frame |
|---|---|
| Disease Control Rate (DCR);Safety;Overall survival (OS);Progression-Free Survival; | — |
Countries
China
Contacts
Public ContactTan Deng
Hunan Provincial People's Hospital
Outcome results
None listed