Phase 2 Trial of Adjuvant Adebrelimab Combined With Capecitabine in High-Risk Resected Cholangiocarcinoma: ACHIEVE (ACHIEVE)

January 14, 2025 updated by: The First Affiliated Hospital with Nanjing Medical University

A Phase 2, Randomized, Controlled, Multicenter Study of Adjuvant Adebrelimab Combined With Capecitabine in Resected Cholangiocarcinoma With High-risk Factors: ACHIEVE

Biliary tract malignancies (BTC) are malignant tumors that originate from the epithelium of the bile ducts. Currently, the optimal treatment for biliary tract malignancies is radical surgical resection. In recent years, with the advancement of imaging technology and surgical techniques, there has been certain progress in the diagnosis and treatment of biliary tract malignancies. However, the surgical resection rate and long-term survival rate after surgery are still not satisfactory, and the high postoperative recurrence rate is an important factor affecting the long-term survival of patients. Therefore, there is an urgent need to explore new postoperative adjuvant treatment plans to reduce postoperative tumor recurrence, which is of great significance for extending the survival of patients with biliary tract malignancies. In the NCCN and CSCO guidelines, capecitabine is listed as a category I recommendation for adjuvant treatment of biliary tract malignancies (BTC). However, in clinical practice, the use of capecitabine or tegafur for postoperative patients with cholangiocarcinoma at high risk of recurrence still has a high recurrence rate. Therefore, there is still a huge unmet need in the clinical adjuvant treatment after surgery for biliary tract malignancies. Based on the above background, we plan to carry out a randomized, open, and comparative study to observe the efficacy and safety of Adebrelimab combined with capecitabine for adjuvant treatment in patients with biliary tract malignancies after surgery, and to explore treatment methods to improve the efficacy of postoperative adjuvant treatment for cholangiocarcinoma.

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

Postoperative adjuvant therapy for biliary system tumors has long lacked a universally recognized standard regimen. The BILCAP trial results showed a survival benefit with adjuvant therapy. The BILCAP study filled the gap in the field of postoperative adjuvant therapy for biliary system tumors. In the study, the median overall survival (OS) in the capecitabine group was 51.1 months, compared to 36.4 months in the observation group. The median recurrence-free survival (RFS) in the capecitabine group was 24.4 months, compared to 17.5 months in the observation group. Compared to the observation group, adjuvant therapy with capecitabine significantly prolonged both OS and RFS, and the capecitabine group had good tolerability with no chemotherapy-related deaths. In addition, the ASCOT study reported that adjuvant therapy with tegafur after surgery could prolong the RFS rate in patients. Therefore, in the NCCN and CSCO guidelines, capecitabine is listed as a category I recommendation for adjuvant therapy of biliary tract malignancies (BTC). However, it is regrettable that the latest reports show that in the intention-to-treat (ITT) population, the BILCAP trial failed to reach its primary endpoint of OS, with the median OS in the study group and the control group being 51.1 months and 36.4 months, respectively [HR=0.81, 95% CI(0.63,1.04), P=0.097]. Furthermore, in clinical practice, the use of capecitabine or tegafur after surgery in patients with cholangiocarcinoma at high risk of recurrence still has a high recurrence rate. Therefore, there is still a significant unmet need in the clinical postoperative adjuvant therapy for biliary tract malignancies.Based on the above background, we plan to carry out a randomized, open, and comparative study to observe the efficacy and safety of Adebrelimab combined with capecitabine for adjuvant treatment in patients with biliary tract malignancies after surgery, and to explore treatment methods to improve the efficacy of postoperative adjuvant treatment for 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 (Estimated)

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.
122

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

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.
  • Name: Xiangcheng Li, Prof. M.D.
  • Phone Number: 86 18951999088
  • Email: drlixc@163.com

Study Contact Backup

  • Name: Changxian Li, Prof. M.D.
  • Phone Number: 86 18761854602
  • Email: doclicx20@163.com

Study Locations

  • China
    • Jiangsu
      • Nanjing, Jiangsu, China, 210000
        • Not yet recruiting
        • Jinling Hospital
        • Contact:
        • Sub-Investigator:
          • Yuan Cheng, MD
      • Nanjing, Jiangsu, China, 210002
        • Recruiting
        • The First Affiliated Hospital of Nanjing Medical University
        • Contact:
        • Sub-Investigator:
          • Changxian Li, MD
      • Xuzhou, Jiangsu, China, 240000
        • Not yet recruiting
        • The Affiliated Hospital of Xuzhou Medical University
        • Contact:
        • Sub-Investigator:
          • Bin Zhang, MD
      • Yancheng, Jiangsu, China, 280000
        • Not yet recruiting
        • Yancheng No.1 People's Hospital
        • Contact:
        • Sub-Investigator:
          • YOnghua Xu, MD

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

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Patients must sign an informed consent form;
  2. Ages 18-75, both genders eligible;
  3. ECOG performance status score (PS score) of 0 or 1;

  4. Patients with histologically confirmed cholangiocarcinoma (including intrahepatic cholangiocarcinoma and hilar cholangiocarcinoma), who have undergone R0 resection and have high-risk factors for recurrence;

    High-risk factors are defined as follows:

    Intrahepatic cholangiocarcinoma ( Single tumor > 5 cm, multiple tumors, liver capsule breach, vascular invasion, regional lymph node metastasis) Hilar cholangiocarcinoma (Tumor invasion into surrounding tissues, vascular invasion, regional lymph node metastasis)

  5. No evidence of recurrence or metastatic lesions on imaging within 28 days prior to randomization;
  6. No prior systemic anti-cancer therapy (including radiotherapy, chemotherapy, targeted therapy, immunotherapy) before curative resection;

  7. Laboratory test values within 7 days prior to the first dose of study medication meet the following criteria:

    Complete blood count: (except for hemoglobin, no blood transfusion or use of granulocyte colony-stimulating factor [G-CSF], no medication correction within 2 weeks prior to screening):

    Absolute neutrophil count ≥1.5×109/L; Platelets ≥75×109/L; Hemoglobin ≥90 g/L;

    Biochemical tests:

    Serum albumin ≥30g/L; Serum total bilirubin ≤1.5×ULN; ALT and AST ≤3×ULN; Serum creatinine ≤1.5×ULN; or Cr clearance rate >50 mL/min International normalized ratio (INR) ≤1.2 or prothrombin time (PT) exceeding the normal control range by ≤2 seconds; Urine protein <2+ (if urine protein ≥2+, a 24-hour (h) urine protein quantification can be performed, and a 24h urine protein quantification of <1.0g is eligible for enrollment);

  8. Life expectancy of more than 6 months.

Exclusion Criteria:

  1. Pathological diagnosis of mixed hepatocellular carcinoma and other non-hepatic extra-bile duct cholangiocarcinoma or ampulla of Vater malignant tumor components;
  2. History of prior systemic treatment;
  3. History of or concurrent other malignancies, excluding non-melanoma skin cancer, cervical carcinoma in situ, and papillary thyroid carcinoma that have been adequately treated;
  4. Active tuberculosis infection. Patients with active tuberculosis infection within 1 year prior to enrollment; history of active tuberculosis infection more than 1 year prior to enrollment without proper anti-tuberculosis treatment or tuberculosis is still active;
  5. History of autoimmune diseases or immunodeficiency, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener's granulomatosis, Sjogren's syndrome, Guillain-Barre syndrome, or multiple sclerosis;
  6. Requirement for long-term systemic corticosteroids (dosage equivalent to >10mg prednisone/day) or any other form of immunosuppressive treatment. Subjects using inhaled or topical corticosteroids may be included;
  7. Severe cardiopulmonary or renal dysfunction;
  8. Inadequately controlled arterial hypertension (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg) (based on the average of ≥2 blood pressure readings), allowing the achievement of the above parameters through the use of antihypertensive treatment; history of hypertensive crisis or hypertensive encephalopathy;
  9. Within 3 months prior to enrollment, significant clinical bleeding symptoms or a clear tendency to bleed; abnormal coagulation function (PT >14s), tendency to bleed, or undergoing thrombolytic or anticoagulant therapy;
  10. HBV DNA >2000 IU/ml, active HCV infection (positive HCV antibody and HCV-RNA level above the lower limit of detection);
  11. Active infection requiring systemic treatment;
  12. Human immunodeficiency virus (HIV, HIV1/2 antibody) positive;
  13. History of psychiatric medication abuse, alcoholism, or drug addiction;
  14. History of allergy to study medication;
  15. Other factors deemed by the investigator to potentially affect subject safety or trial compliance. Such as severe diseases requiring concurrent treatment (including psychiatric diseases), severe laboratory test abnormalities, or other family or social factors.

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: 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.
Experimental: Adebrelimab and capecitabine
Drug: Adebrelimab and capecitabine
Adebrelimab: 1200mg, IV, q3w for one year; capecitabine:1250mg/m2, po, bid,d1-14, q3w, for 6-8 cycles
Active Comparator: capecitabine
Drug: capecitabine
capecitabine:1250mg/m2, po, bid,d1-14, q3w, for 6-8 cycles

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
one year recurrence free survival rate (1-year RFS)
Time Frame: 1 year
1-year RFS refers to the proportion of patients who have not experienced disease recurrence or death within one year from randomization.
1 year

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 (OS)
Time Frame: 3 year
Overall survival (OS) refers to the length of time from randomization until death from any cause.
3 year
Recurrence free survival (RFS)
Time Frame: 2 year
Recurrence-free survival (RFS) refers to the length of time after randomization during which a patient remains free from the recurrence of the disease.
2 year
minimal residual disease (MRD)
Time Frame: 2 year
MRD refers to tumor-derived molecular abnormalities that are undetectable by imaging or traditional laboratory methods after treatment, but can be identified through liquid biopsy.
2 year

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.
The First Affiliated Hospital with Nanjing Medical University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Jinling Hospital, China

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.
September 20, 2024

Primary Completion (Estimated)

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.
September 20, 2026

Study Completion (Estimated)

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.
September 20, 2027

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).
September 19, 2024

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.
September 19, 2024

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.
September 23, 2024

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.
March 25, 2025

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.
January 14, 2025

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.
January 1, 2025

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.
  • 2024-SR-571

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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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