Camrelizumab and Chemotherapy With or Without Anlotinib as First-line Treatment for Advanced Gallbladder Cancer and Extrahepatic Cholangiocarcinoma

NCT06901622 | Enrolling By Invitation Phase 2

• 1 other identifier: BTC-02
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

To evaluate the efficacy and safety of camrelizumab and chemotherapy with or without anlotinib as first-line treatment for advanced gallbladder cancer and extrahepatic cholangiocarcinoma

Conditions

Gallbladder Cancer and Extrahepatic Cholangiocarcinoma

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate, ORR

  The RECIST1.1 standards were used to evaluate the efficacy of drugs.

  Time Frame: about 2 years

Secondary Outcomes (6)

• Disease Control Rate, DCR

  Time Frame: about 2 years

• Progression Free Survival, PFS

  Time Frame: about 2 years

• Event Free Survival, EFS

  Time Frame: about 2 years

• 2-year Overall Surviva rate

  Time Frame: about 2 years

• Surgical resection rate

  Time Frame: about 2 years

Study Arms (2)

Cohort 1

EXPERIMENTAL

Camrelizumab, anlotinib, nab-paclitaxel, S-1

Drug: Camrelizumab, anlotinib, nab-paclitaxel, S-1

Cohort 2

EXPERIMENTAL

Camrelizumab, nab-paclitaxel, S-1

Drug: Camrelizumab, nab-paclitaxel, S-1

Interventions

Camrelizumab, anlotinib, nab-paclitaxel, S-1 DRUG

Initial treatment (4 cycles) Carrelizumab: 200 mg, day 1, iv, q3w. Anlotinib: 10 mg, taken orally once a day, day 1\~14, q3w. For patients with intolerance, the dose can be reduced to 8 mg. Nab-paclitaxel: 200 mg/m\^2, day 1, iv, q3w. (Patients with poor tolerance can be given on the 1st and 8th days, and the total dosage remains unchanged). S-1: 60 mg/day for body surface area \<1.25 m\^2; 80 mg/day for body surface area = 1.25\~1.50 m\^2; 100 mg/day for body surface area \>1.50 m\^2; 2 times a day, administered on days 1 to 14, 3 weeks as a treatment cycle. After 4 cycles of initial treatment, the feasibility of surgery was evaluated. Operable patients: radical surgical resection, followed by 4 cycles of S-1 combined with carrelizumab (up to 1 year). During postoperative treatment, the investigator determined whether local radiotherapy (CCRT) was required. Inoperable patients: carrelizumab + anlotinib + S-1 were treated until intolerance or disease progression.

Cohort 1

Camrelizumab, nab-paclitaxel, S-1 DRUG

Initial treatment (4 cycles) Carrelizumab: 200 mg, day 1, intravenous drip, 3 weeks as a treatment cycle. Nab-paclitaxel: 200 mg/m\^2, day 1, intravenous drip, 3 weeks as a treatment cycle. (Patients with poor tolerance can be given on the 1st and 8th days, and the total dosage remains unchanged). S-1: 60 mg/day for body surface area \<1.25 m\^2; 80 mg/day for body surface area = 1.25\~1.50 m\^2; 100 mg/day for body surface area \>1.50 m\^2; 2 times a day, administered on days 1 to 14, 3 weeks as a treatment cycle. After 4 cycles of initial treatment, the patient's surgical feasibility was evaluated. Operable patients: radical surgical resection, followed by S-1 (4 cycles) combined with carrelizumab treatment (up to 1 year). During postoperative treatment, the investigator determined whether local radiotherapy (CCRT) was required. Inoperable patients: carrelizumab + S-1 treatment until intolerance or disease progression.

Cohort 2

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \) Patients voluntarily join this study, sign informed consent, and have good compliance;
• \) Age: 18 to 75 years old, both men and women;
• \) Unresectable locally advanced, unresectable recurrent or metastatic gallbladder cancer or extrahepatic bile duct cancer confirmed by pathological histology, and have not received systemic treatment; (according to RECIST version 1.1, at least one measurable lesion), tissue samples must be provided for biomarker analysis, and newly obtained tissues are preferred. Patients who cannot provide newly obtained tissues can provide 5-8 5um thick paraffin sections preserved in archives;
• \) ECOG score: 0-1 points;
• \) Estimated survival period ≥12 weeks;
• \) Adequate organ function, and the following laboratory test values are required at the time of screening:
• ①Routine blood test standards must meet the following: Hemoglobin content (HB) ≥90g/L (no blood transfusion within 14 days); Absolute neutrophil count (ANC) ≥1.5×10\^9/L; Platelet count (PLT) ≥80×10\^9/L (no interleukin 11 or TPO used within 14 days); White blood cell count (WBC) ≥4.0×10\^9/L (no granulocyte stimulating factor used within 14 days).
• ② Biochemical examinations must meet the following criteria: Serum total bilirubin (TBIL) ≤1.5 times the upper limit of normal (ULN); ALT and AST ≤2.5 ULN; Cr ≤1.5 ULN or creatinine clearance (CCr) ≥60 ml/min, (Cockcroft-Gault formula); Serum albumin ≥ 25 g/L (2.5 g/dL)
• \) Doppler ultrasound assessment: left ventricular ejection fraction (LVEF) ≥ lower limit of normal (50%);
• \) Adequate coagulation function, defined as international normalized ratio (INR) or prothrombin time (PT) ≤1.5 times ULN;
• )Females of childbearing potential must take effective contraceptive measures during the study and for at least 6 months after the last dose and chemotherapy. It is recommended to start taking contraceptive measures at least 3 months before the administration of the study drug; males who have not been sterilized must take effective contraceptive measures during the study and for at least 6 months after the last dose and chemotherapy. Contraceptive measures are recommended to be initiated at least 3 months before study drug administration.

You may not qualify if:

• \) Patients who have received anlotinib hydrochloride treatment or any anti-PD-1, anti-PD-L1, anti-CTLA-4 antibody treatment in the past;
• \) Patients with a history of immunodeficiency, including HIV positive or other acquired or congenital immunodeficiency diseases, or a history of organ transplantation;
• \) Patients with active hepatitis B or C, active pulmonary tuberculosis;
• \) Patients with liver metastasis burden accounting for more than 50% of the total liver volume;
• \) CT showed clear ulcerative lesions or positive stool occult blood;
• \) Self-reported history of abnormal bleeding (excluding epistaxis) one month before enrollment;
• \) Patients who have received allogeneic bone marrow transplantation or organ transplantation in the past;
• \) Congenital pulmonary fibrosis, drug-induced pneumonia, organizing pneumonia, or active pneumonia confirmed by CT;
• \) Injection of live attenuated vaccine within 4 weeks before the start of the study, or expected to be injected with live attenuated vaccine during the trial or within 5 months after the end of the trial;
• \) Systemic application of glucocorticoids or immunosuppressants within 2 weeks before the start of the trial (Note: inhaled glucocorticoids and mineralocorticoids are allowed);
• \) Multiple factors that affect oral medication (such as inability to swallow, chronic diarrhea and intestinal obstruction, etc.);
• \) ≥ NCI CTCAE grade 2 peripheral neuropathy;
• \) Infection requiring antibiotics within 14 days before the start of the trial;
• \) Patients with any severe and/or uncontrolled diseases, including: Patients with poor blood pressure control using antihypertensive drugs (systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥100 mmHg); patients with grade II or above myocardial ischemia or myocardial infarction, arrhythmia (including QT interval ≥480ms); patients with grade III-IV heart failure according to NYHA standards, or left ventricular ejection fraction (LVEF) \<50% indicated by cardiac ultrasound examination; Active or uncontrolled severe infection; Liver disease such as cirrhosis, decompensated liver disease, chronic active hepatitis; Poorly controlled diabetes (fasting blood glucose (FBG) \>10mmol/L); Urinalysis indicates urine protein ≥++, and confirms that the 24-hour urine protein quantification is \>1.0 g;
• \) Long-term unhealed wounds or fractures;

Sponsors & Collaborators

• The First Affiliated Hospital of Zhengzhou University: lead

Study Sites (1)

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, 450000, China

Location

MeSH Terms

Conditions

Gallbladder Neoplasms; Cholangiocarcinoma

Interventions

camrelizumab; anlotinib; 130-nm albumin-bound paclitaxel; S 1 (combination)

Condition Hierarchy (Ancestors)

Biliary Tract Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases; Gallbladder Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Model Details: Randomized Double-cohort Study

Study Record Dates

• First Submitted: September 2, 2024
• First Posted: March 30, 2025
• Study Start: November 8, 2024
• Primary Completion: March 1, 2026
• Study Completion (Estimated): July 1, 2027
• Last Updated: March 30, 2025

Record last verified: 2024-11

Locations

CN (1)