Camrelizumab Combined With Apatinib and Capecitabine in Patients With Advanced Biliary Tract Cancer.

NCT04720131 | Completed Phase 2

• 1 other identifier: BFH-BTC＆PD-1
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

Biliary tract cancer (BTC) is a series of rare malignancies with poor overall prognosis. Radical surgery the preferred treatment option, but most patients have lost the opportunity of surgery at the time of diagnosis. At present, there are limited systematical treatment options for biliary tract cancer, with poor efficacy and short duration of responses. In the past few years, immune checkpoint inhibitors (ICIs) therapy has gradually been added to the advanced biliary comprehensive treatment. However, in view of the low incidence and high heterogeneity of BTC, more large number of clinical trials and practices need to be carried out, and the effective combination regimens and predictive biomarkers need to be explored. This study is a single-arm, open-label, prospective cohort study, combining Camrelizumab with apatinib and capecitabine as the first-line or second-line treatment for patients with advanced biliary tract cancer. The study aims to explore the efficacy and safety of the combination regimen, and try to find biomarkers that can guild treatment. In this study, 34 patients were enrolled by the Simon's two-stage design, with the objective response rate as the primary endpoint and the disease control rate, progression-free survival, overall survival and safety as secondary endpoints. It is expected that the three-drug combination regimen will have significant efficacy and manageable adverse reactions, and predictive biomarkers can be found.

Conditions

Biliary Tract Cancer; Anti-PD-1 Therapy; Targeted Molecular Therapy; Capecitabine

Keywords

Capecitabine; Targeted Molecular Therapy; Biliary Tract Cancer; Camrelizumab

Outcome Measures

Primary Outcomes (1)

• Objective response rate

  The proportion of patients with measurable disease who achieved complete response (CR) or partial response (PR)

  30 months

Secondary Outcomes (4)

• Disease Control Rates (DCR)

  30 months

• Progression-Free Survival

  30 months

• Overall Survival

  30 months

• Safety

  30 months

Study Arms (1)

Camrelizumab combined with Apatinib and Capecitabine

EXPERIMENTAL

Camrelizumab was administered 200mg iv every 3 weeks. Capecitabine was administered 1000mg/m2 orally, b.i.d. every 3 weeks (Day 1-14 of a treatment cycle) Apatinib:A safety-run-in was conducted in the first cycle to identify the recommended dose of Apatinib, the initial dose was administered 250mg orally daily every 3 weeks (Day 1-14 of a treatment cycle). The dose of Apatinib increase and reduction was 250 mg orally q.d. and 250 mg orally q.o.d. every 3 weeks respectively according to the number of doses limiting toxicity events (DLTs) in the initial group. The final dose of Apatinib for the extension stage was detemained by the result of safety-run-in stage.

Drug: Camrelizumab; Drug: apatinib; Drug: Capecitabine

Interventions

Camrelizumab DRUG

Camrelizumab was administered 200mg iv every 3 weeks.

Camrelizumab combined with Apatinib and Capecitabine

apatinib DRUG

Apatinib A safety-run-in was conducted in the first cycle to identify the recommended dose of Apatinib, the initial dose was administered 250mg orally daily every 3 weeks (Day 1-14 of a treatment cycle) The dose of Apatinib increase and reduction was 250 mg orally q.d. and 250 mg orally q.o.d. every 3 weeks respectively according to the number of doses limiting toxicity events (DLTs) in the initial group. The final dose of Apatinib for the extension stage was detemained by the result of safety-run-in stage.

Camrelizumab combined with Apatinib and Capecitabine

Capecitabine DRUG

Capecitabine was administered 1000mg/m2 orally, b.i.d. every 3 weeks (Day 1-14 of a treatment cycle)

Camrelizumab combined with Apatinib and Capecitabine

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18-70 years old, both genders.
• Conform to the histological or cytological confirmation of biliary tract carcinoma，including gallbladder cancers and cholangiocarcinomas.
• Patients have advanced unresectable biliary tract carcinoma, including recurrence or metastasis of BTC after radical resection.
• Patientss who have not received any prior PD-1 inhibitor and Apatinib therapy.
• Patients must have at least 1 lesion that is measurable using RECIST v1.1 criteria.
• Eastern Cooperative Oncology Group Performance Status of 0 or 1within one week before enrollment.
• Life expectancy greater than 3 months.
• Patient must have adequate organ function defined by the study-specified laboratory tests.
• Patient must use acceptable form of birth control while on study.
• Ability to understand and willingness to sign a written informed consent document.

You may not qualify if:

• Patients with known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation or planned transplantation.
• Patients with other malignant tumor in the past 5 years (except cured skin basal cell carcinoma and cervical carcinoma).
• History of esophageal variceal bleeding, hepatic encephalopathy, massive ascites and abdominal infection.
• Concurrent medical condition requiring the use of immunosuppressive medications, or immunosuppressive doses of systemic or absorbable topical corticosteroids. Doses \> 10 mg/day prednisone or equivalent are prohibited within 14 days before study drug administration.
• Known history of hypersensitivity to any components of the camrelizumab, apatinib and Capecitabine formulation, or other antibody formulation.
• Patients who may receive live vaccine during the study, or previous had vaccination within 4 weeks.
• Known or occurrence of central nervous system (CNS) metastases or hepatic encephalopathy.
• Peripheral neuropathy\> Grade 1.
• Patients with any active autoimmune disease or history of autoimmune disease.
• History of immunodeficiency or human immunodeficiency virus (HIV) infection.
• Clinically significant cardiovascular and cerebrovascular diseases, including but not limited to severe acute myocardial infarction within 6 months before enrollment, unstable or severe angina, or coronary artery bypass surgery, Congestive heart failure (New York heart association (NYHA) class \> 2), ventricular arrhythmia which need medical intervention.
• Hypertension and unable to be controlled within normal level following treatment of anti-hypertension agents (within 3 months): systolic blood pressure \> 140 mmHg, diastolic blood pressure \> 90 mmHg.
• Coagulation abnormalities (INR\>1.5 or APTT\>1.5×ULN), with bleeding tendency or are receiving thrombolytic or anticoagulant therapy.
• History of hereditary or acquired bleeding and thrombotic tendency, such as hemophilia, coagulopathy, thrombocytopenia, hypersplenism, etc.
• Patients with obvious cough blood or hemoptysis volume of half teaspoon (2.5 ml) or more within 2 months before entering the study.

Sponsors & Collaborators

• Beijing Friendship Hospital: lead

Study Sites (1)

Beijing Friendship Hospital

Beijing, Beijing Municipality, 100050, China

Location

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MeSH Terms

Conditions

Biliary Tract Neoplasms

Interventions

camrelizumab; apatinib; Capecitabine

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Wei Deng

  Department of General Surgery, Beijing Friendship Hospital, Capital Medical University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: professor

Study Record Dates

• First Submitted: January 20, 2021
• First Posted: January 22, 2021
• Study Start: January 1, 2021
• Primary Completion: April 30, 2023
• Study Completion: May 30, 2023
• Last Updated: January 30, 2024

Record last verified: 2024-01

Locations

CN (1)