Low-dose Gemcitabine and Cisplatin and PD-1/PD-L1 Antibody Therapy in Intrahepatic Cholangiocarcinoma

August 20, 2024 updated by: Linsen Ye, Third Affiliated Hospital, Sun Yat-Sen University

Combined Therapy Using Low-dose Gemcitabine and Cisplatin Chemotherapy and PD-1/PD-L1Antibody for Patients With Advanced and Unresectable Intrahepatic Cholangiocarcinoma: an Open-label, Multicenter, Single-arm Clinical Trial

In this phase 2 study, researchers aimed to evaluate the efficacy and safety of low-dose gemcitabine and cisplatin chemotherapy and the immune checkpoint inhibitor PD-1/PD-L1 antibody in patients with advanced and unresectable intrahepatic cholangiocarcinoma.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet 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

More and more studies suggest that low-dose chemotherapy has the ability to reshape the tumor microenvironment and promote tumor immunotherapy in a variety of tumors, supporting the rationality of combining low-dose chemotherapy with immunotherapy to effectively treat tumors with low T cell infiltration. More than half of intrahepatic cholangiocarcinomas are non-inflammatory "cold tumors", and their unique immunosuppressive microenvironment is one of the reasons for the poor response rate to immunotherapy. Low-dose chemotherapy can transform "cold" tumors with low immunogenicity and poor immune cell infiltration into "hot" tumors with immune responsiveness and sufficient immune cell infiltration, enhance the effect of ICIs on tumor cells, and minimize systemic toxicity, thus preserving a "therapeutic window" for combined immunotherapy/targeted therapy. Preclinical and clinical studies have shown that it is necessary to study the optimal dose of chemotherapeutic drugs in combination therapy. In combination therapy, long-term, adequate doses of chemotherapeutic drugs may be unnecessary because this will not only lead to more severe toxicity, but also damage rather than enhance anti-tumor immunity.

To determine the efficacy and safety of low-dose chemotherapy combined with PD-1/PD-L1 inhibitors in the treatment of patients with advanced intrahepatic cholangiocarcinoma, we designed an open-label, prospective, multicenter, single-arm clinical study of low-dose gemcitabine + cisplatin combined with PD-1/PD-L1 inhibitors in the treatment of patients with advanced intrahepatic 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.
43

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.

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China
        • The Third Affiliated Hospital Of Sun Yat-Sen University

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. Age ≥ 18 years old, male or female;
  2. Histopathologically confirmed intrahepatic cholangiocarcinoma;
  3. TNM Staging≥Stage II (American Joint Committee on Cancer Prognostic Groups)
  4. Presence of at least one measurable lesion assessed using the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST version 1.1);
  5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  6. Child-Pugh score ≤ 7;
  7. Adequate organ function (neutrophil count of ≥1.5×10^9 cells/L, hemoglobin concentrations of ≥90 g/L, platelet cell count of ≥100×10^9 cells/L, bilirubin ≤1.5×ULN, Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) ≤ 5×ULN, serum creatinine ≤ 1.5 x ULN, Thyroid stimulating hormone (TSH) ≤ 1 x ULN;
  8. The patient must be required to sign an informed consent form;

Exclusion Criteria:

  1. Patients who have received previous treatment with interventional therapy, radiotherapy, ablation, chemotherapy, targeted therapy, immunotherapy (PD-1, PD-L1, CLTA-4 antibody, etc), or surgery within the last 2 months;
  2. Patients with other malignant tumors within the last 5 years, except for cured non-melanoma skin cancer, cervical carcinoma in situ, and papillary thyroid carcinoma;
  3. Active tuberculosis infection. Patients with active tuberculosis infection within 1 year prior to enrollment; had a history of active tuberculosis infection more than 1 year before enrollment, did not receive formal anti-tuberculosis treatment or tuberculosis is still active;
  4. Active infection requiring systemic therapy;
  5. Human immunodeficiency virus (HIV) positive;
  6. Have an active, known, or suspected autoimmune disease. Subjects who require only hormone replacement therapy for hypothyroidism and skin diseases that do not require systemic therapy may be enrolled;
  7. Suffering from high blood pressure, and can not be well controlled by antihypertensive drugs (systolic blood pressure ≥140mmHg or diastolic blood pressure ≥90mmHg);
  8. Abnormal blood coagulation (INR >1.5, or PT>ULN+4s, or APTT >1.5 x ULN), with a bleeding tendency or receiving thrombolytic or anticoagulant therapy;
  9. Pregnant or lactating women;
  10. Participated in other trials within the last 4 weeks;
  11. Has a history of allergy to platinum;
  12. Other factors that may influence the safety of the subject or the compliance of the test by the investigator. Serious illnesses (including mental illness), severe laboratory tests, or other family or social factors that require combined 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: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group 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: Low-dose Gemcitabine and Cisplatin Chemotherapy plus PD-1/PD-L1Antibody

Low-dose Gemcitabine and Cisplatin Chemotherapy:

Gemcitabine 500 mg/m2 Cisplatin 12.5 mg/m2 on day 1 and day 8 of each 21-day cycle for up to eight cycles

PD-1/PD-L1Antibody:

Pembrolizumab 200mg on day 1 of each 21-day cycle Durvalumab 1500 mg on day 1 of each 21-day cycle After completion of gemcitabine and cisplatin, 200mg of Pembrolizumab or 1500 mg of Durvalumab may administer once every 3 or 4 weeks until clinical or imaging (per RECIST v1.1) disease progression or until unacceptable toxicity, withdrawal of consent, or any other discontinuation criteria were met.
Drug: Low-dose Gemcitabine and Cisplatin Chemotherapy plus PD-1/PD-L1Antibody

Low-dose Gemcitabine and Cisplatin Chemotherapy:

Gemcitabine 500 mg/m2 Cisplatin 12.5 mg/m2 on day 1 and day 8 of each 21-day cycle for up to eight cycles

PD-1/PD-L1Antibody:

Pembrolizumab 200mg on day 1 of each 21-day cycle Durvalumab 1500 mg on day 1 of each 21-day cycle After completion of gemcitabine and cisplatin, 200mg of Pembrolizumab or 1500 mg of Durvalumab may administer once every 3 or 4 weeks until clinical or imaging (per RECIST v1.1) disease progression or until unacceptable toxicity, withdrawal of consent, or any other discontinuation criteria were met.

Other Names:
  • LDGC-PB

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
Objective Response Rate (ORR)
Time Frame: 12 months
ORR according to RECIST 1.1 using investigator assessment
12 months

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
Incidence of adverse events
Time Frame: 12 months
Rate of participants with treatment-related adverse events as assessed by CTCAE v4.0
12 months
Deepness of response (DpR)
Time Frame: 12 months
DpR according to RECIST 1.1 using investigator assessment
12 months
Disease control rate (DCR)
Time Frame: 12 months
DCR according to RECIST 1.1 using investigator assessment
12 months
Overall Survival (OS)
Time Frame: 36 months
OS is defined as the time from date of combined theray start to the date of death from any cause or to the date of last follow-up if patients are alive
36 months
Progression-free Survival (PFS)
Time Frame: 36 months
From the beginning date of combined therapy to the date of disease progression. PFS according to RECIST 1.1 using investigator assessment
36 months

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.
Third Affiliated Hospital, Sun Yat-Sen 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.
Second Affiliated Hospital of Guangzhou Medical University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Ye Linsen, Professor, The third affiliated hospital of SYSU

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 (Estimated)

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 1, 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.
December 31, 2027

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.
December 31, 2028

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).
August 20, 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.
August 20, 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.
August 22, 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.
August 22, 2024

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 20, 2024

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, 2024

More Information

Terms related to this study

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.
  • ZSSY-2407

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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