Adjuvant PD-1 Antibody in Combination With Capecitabine for Patients With ICC at High-Risk of Postoperative Recurrence

August 16, 2022 updated by: Lunxiu Qin, Fudan University

Adjuvant PD-1 Antibody（Tislelizumab） in Combination With Capecitabine for Patients With Cholangiocarcinoma at High-Risk of Postoperative Recurrence

The purpose of the study is to observe the effect of PD-1 Antibody（Tislelizumab） Combined With Capecitabine as Adjuvant Therapy to Prevent the Recurrence in High-risk Patients With Cholangiocarcinoma After Curative Resection.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Cholangiocarcinoma has a low incidence, accounting for only 3% of gastrointestinal malignancies worldwide, but with an increasing trend in recent years.Cholangiocarcinoma is extremely malignant, and the 5-year survival rate for patients who cannot undergo curative resection at advanced stages is less than 10%. Surgical resection represents the only curative opportunity for biliary tract cancer, but only 1 5% - 20% of patients can undergo surgical resection; however, even patients who undergo curative surgical resection have a high rate of postoperative metastasis recurrence, and effective treatment strategies are lacking after metastasis recurrence.The median postoperative survival time is only 18-30 months and the 5-year survival rate is also only 20-35%.Among them, patients with high-risk postoperative recurrence who are resected but have positive lymph nodes or margins have further reduced survival, and no targeted effective postoperative adjuvant therapy is available, becoming another important reason that hampers the long-term survival of surgical patients.

For unresectable or advanced cholangiocarcinoma, GEMOX, a two drug combination regimen of gemcitabine plus cisplatin, can be used as a first-line chemotherapy regimen, but the first-line regimen of postoperative adjuvant chemotherapy is currently not uniformly recommended.Previous adjuvant chemotherapy for cholangiocarcinoma was mostly based on clinical experience from different medical centers and borrowed in view of gemcitabine - and platinum based advanced regimens, but the conclusions based on retrospective studies varied greatly among different centers and the recommendation was limited.Whereas there are fewer prospective studies aiming to target postoperative adjuvant chemotherapy for cholangiocarcinoma.The 2017 Prodige prospective randomized controlled study evaluated the efficacy of GEMOX in advanced cholangiocarcinoma in 196 patients treated with postoperative adjuvant chemotherapy and showed that although there was a trend toward benefit in RFs, it was not statistically significant overall and does not support the use of the GEMOX regimen in advanced cholangiocarcinoma in the postoperative adjuvant setting.While another 2018 bcat prospective study negated the clinical benefit of gemcitabine monotherapy in postoperative adjuvant chemotherapy for cholangiocarcinoma.In contrast, the 2017 Bilcap study was the only one to yield positive results in postoperative adjuvant chemotherapy for cholangiocarcinoma.The study compared the clinical value of capecitabine with clinical observation in postoperative adjuvant chemotherapy for cholangiocarcinoma, the primary endpoint was OS, the secondary endpoints included OS, recurrence free survival (RFs), etc. adjuvant capecitabine can extend the OS of postoperative cholangiocarcinoma from 36 to 51 months, and in terms of safety, the differences in toxicity between the capecitabine combination control groups were not significant and most of themNumber patients could tolerate.Therefore, the ASCO guidelines also recommend adjuvant chemotherapy with capecitabine in patients with cholangiocarcinoma after surgery and recommend it as a control for subsequent clinical studies in cholangiocarcinoma.However, whether capecitabine monotherapy can play a role in preventing recurrence in patients with high-risk disease who have undergone surgery with positive lymph nodes or resection margins remains to be confirmed by further studies.

Cholangiocarcinoma is accompanied by a dysregulation and remodelling of the local immune microenvironment, and therefore the catalysed tumour immunotherapy has been a long-standing hotspot in the field of cancer therapy, in which T-cell-based tumour immunotherapy is in its core position. 1 cancer immunotherapy is fully used and mobilising killer T cells from the tumour bearing patient. 2Cells, to carry out the killing effect on the tumor, it may be the most effective and the safest way to treat the tumor.At the same time, tumor escape is a formidable obstacle facing tumor immunotherapy, in which tumor cells exploit their own suppressive effects on the immune system to promote deranged tumor growth.There is an extremely complex relationship between the immune escape mechanism of tumors and the host immune response to tumors.Tumor immunotherapy tumor specific killer T cells in the early stage are biologically active, but lose the function of killing as the tumor grows later.So tumor immunotherapy is to maximize the patient's own immune system reaction against tumors, and it is not only necessary to activate the original immune system reaction in vivo, but also to maintain the duration and intensity of the reaction, which is the key to immunotherapy against tumors.The 2017 FDA approval of the immune checkpoint inhibitor PD-1 inhibitor pembrolizumab for patients with MSI-H / dMMR pan tumors laid the groundwork for immunotherapy in cholangiocarcinoma.In the current clinical study of advanced cholangiocarcinoma, the combination regimen of PD-1 inhibitor + FOLFOX4 / GEMOX demonstrated a favorable survival benefit with an acceptable safety profile in advanced cholangiocarcinoma.Tirelizumab (Baiji Shenzhou) is a humanized lgg4 anti programmed death receptor 1 (PD-1) monoclonal antibody designed to minimize binding to FC γ r receptors in macrophages.Preclinical data suggest that FC γ r receptor engagement in macrophages is followed by activation of antibody dependent cell-mediated killing of T cells, reducing the antitumor activity of PD-1 antibodies.Tirelizumab is currently under clinical investigation as a single agent and combination therapy worldwide, developing a range of broad indications for both solid tumours and haematological tumours.There are currently 15 potential registered clinical studies of bazea in China and worldwide, including 11 phase 3 studies, four pivotal phase 2 studies.A phase I / II study evaluating the efficacy of tirelizumab monotherapy in Chinese patients with advanced solid tumors across cancer types, using a 200 mg IV q3w dose and dosing schedule, has demonstrated tolerability at this dose in the Chinese population, a favorable clinical safety profile, and no contraindications in combination with chemotherapeutic agents such as capecitabine have been reported.

We plan to conduct a single center prospective interventional cohort study of capecitabine plus PD1 MAb given to patients who have been evaluated for high-risk recurrence after surgery for cholangiocarcinoma, to evaluate its efficacy and safety compared with capecitabine alone, and to strive for an effective treatment option in preventing postoperative metastatic recurrence of cholangiocarcinoma.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
30

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

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

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • China
      • Shanghai, China, 20040
        • Recruiting
        • Lulu@Huashan.Org.Cn
        • Contact:

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Post R0 resection, pathologically confirmed intrahepatic cholangiocarcinoma.Patients were also pathologically confirmed to have any of the following high-risk factors (ie, positive resection margins, positive lymph nodes, positive perineural invasion, and intrahepatic cholangiocarcinoma > 5cm in diameter;
  • No history of any chemotherapy, radiotherapy, immunotherapy and interventional treatment prior to surgical resection;
  • ECoG score 0-1 points;
  • Liver function before medication child a, blood routine: WBC > 2.5 * 109 / L, PLT > 60 * 109 / L, coagulopathy: Pt prolonged < 2S, ALT < 150u / L;
  • No heart, lung, or kidney function abnormalities were observed;
  • No history of major bleeding disorders of the digestive tract;
  • Signed informed consent;

Exclusion Criteria:

  • Pregnant or lactating women.
  • Patients with other malignant tumor.
  • Patients with mental illness.
  • Patients participated in other clinical trials in last three months.
  • Residual lesions showed by Postoperative digital subtraction angiography(DSA).
  • Postoperative patients treated with other targeted drugs, PD1 antibody and other immunotherapies, FOLFOX systemic chemotherapy, and HuaiErKeLi drug treatment

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: Prevention
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Capecitabine
Capecitabine as Adjuvant Therapy Oral capecitabine (1250 mg/m²) was given post operatively twice a day on days 1 to 14 of a 3-weekly cycle for 24 weeks (eight cycles), and observation commenced within 16 weeks of surgery.
Drug: Capecitabine
Capecitabine+PD-1 Antibody（Tislelizumab）as Adjuvant Therapy Oral capecitabine (1250 mg/m²) was given post operatively twice a day on days 1 to 14 of a 3-weekly cycle for 24 weeks (eight cycles), and observation commenced within 16 weeks of surgery.
Other Names:
  • XELODA
Experimental: Capecitabine+PD-1 Antibody（Tislelizumab）
Capecitabine+PD-1 Antibody（Tislelizumab）as Adjuvant Therapy Oral capecitabine (1250 mg/m²) was given post operatively twice a day on days 1 to 14 of a 3-weekly cycle for 24 weeks (eight cycles), and observation commenced within 16 weeks of surgery. PD-1 Antibody（Tislelizumab, 200mg） was given q3w iv.
Drug: Capecitabine
Capecitabine+PD-1 Antibody（Tislelizumab）as Adjuvant Therapy Oral capecitabine (1250 mg/m²) was given post operatively twice a day on days 1 to 14 of a 3-weekly cycle for 24 weeks (eight cycles), and observation commenced within 16 weeks of surgery.
Other Names:
  • XELODA
Drug: PD-1 Antibody（Tislelizumab）
PD-1 Antibody（Tislelizumab, 200mg） was given q3w iv.
Other Names:
  • Tislelizumab

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
recurrence free survival (RFS)
Time Frame: 2 years
the time from liver resection to tumor recurrence or metastasis
2 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: 5 years
the survival time after liver resection
5 years

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Fudan University

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2021

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 30, 2023

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 1, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 3, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 3, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 4, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 18, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 16, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • HUASHAN006

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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