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

January 28, 2024 updated by: Zhongtao Zhang, Beijing Friendship Hospital

Camrelizumab Combined With Apatinib and Capecitabine for Patients With Advanced Biliary Tract Cancer: a Phase 2, Single-arm, Prospective Study.

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

28

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 100050
        • Beijing Friendship Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  • Have significant clinically significant bleeding symptoms or have a clear bleeding tendency within 3 months before entering the study, such as gastrointestinal bleeding, hemorrhagic gastric ulcer, fecal occult blood++ and above at baseline, or vasculitis, etc.
  • Previous Arterial/venous thrombosis events within 6 months.
  • Required for long-term anticoagulant therapy with warfarin or heparin, or long-term antiplatelet therapy (aspirin ≥300 mg/day or clopidogrel ≥75 mg/day).
  • Severe infection within 4 weeks before the first medication (e.g. need for intravenous antibiotics, antifungal or antiviral drugs), or active infection or an unexplained fever > 38.5°C during screening visits or on the first scheduled day of dosing.
  • Participated in any other drug clinical study within 4 weeks before the first administration, or no more than 5 half lives from the last administration.
  • Known history of psychotropic drug abuse or drug abuse.
  • Pregnant and lactating women. Any other medical, psychiatric, or social condition deemed by the investigator to be likely to interfere with a subject's rights, safety, welfare, or ability to sign informed consent, cooperate, and participate in the study or would interfere with the interpretation of the results.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Camrelizumab combined with Apatinib and Capecitabine
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
Camrelizumab was administered 200mg iv every 3 weeks.
Drug: apatinib

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective response rate
Time Frame: 30 months
The proportion of patients with measurable disease who achieved complete response (CR) or partial response (PR)
30 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease Control Rates (DCR)
Time Frame: 30 months
The proportion of patients achieving CR or PR or stable disease (SD)
30 months
Progression-Free Survival
Time Frame: 30 months
The duration from the beginning of the treatment to the disease progression, or death from any cause, or last progression-free survival assessment for patients alive without progression
30 months
Overall Survival
Time Frame: 30 months
The duration from the enrollment to death from any cause
30 months
Safety
Time Frame: 30 months
The incidence of any grade treatment-related adverse events.
30 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Beijing Friendship Hospital

Investigators

  • Principal Investigator: Wei Deng, Department of General Surgery, Beijing Friendship Hospital, Capital Medical University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2021

Primary Completion (Actual)

April 30, 2023

Study Completion (Actual)

May 30, 2023

Study Registration Dates

First Submitted

January 20, 2021

First Submitted That Met QC Criteria

January 20, 2021

First Posted (Actual)

January 22, 2021

Study Record Updates

Last Update Posted (Actual)

January 30, 2024

Last Update Submitted That Met QC Criteria

January 28, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BFH-BTC＆PD-1

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

IPD can be obtained with the consent of the principal investigator

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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