PD-1 Inhibitor Intraperitoneal Perfusion Combined With PRaG Therapy for Malignant Ascites

August 11, 2022 updated by: Second Affiliated Hospital of Soochow University

Phase I-II Clinical Study of PRaG（PD-1 Inhibitor Intravenous Injectio,Radiotherapy and GM-CSF）Combined With PD-1 Inhibitor Intraperitoneal Perfusion for Advanced Refractory Solid Tumors Combined With Malignant Ascites

The effect and safety of intraperitoneal infusion of PD-1 inhibitor is unclear for patients with peritoneal metastasis of advanced malignant tumors and malignant ascites. It is planned to determine the safety and efficacy of intraperitoneal infusion of PD-1 inhibitor combination with PRaG therapy.

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

Patinets with peritoneal metastasis have limited treatment and poor prognosis. Evidence has shown that there are T lymphocates and macrophages in the ascites microenviroment.We suggested the Intraperitoneal infusion of PD-1 inhibitor might activate T cells and produce anti-tumor effect.The intraperitoneal infusion of PD-1 inhibitorand combined with PRaG(Intravenous injectionof PD-1 inhibitor, Radiotherapy and GM-CSF）might benefit the survival of patients with peritoneal metastasis of advanced malignant tumors with malignant ascites. It is planned to determine the safety in phase I clinical trial. Further through phase II clinical trials, to clarify the effectiveness of this therapy.

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.
40

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.

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:

  • Patients > 18 years of age.
  • Pathologically diagnosed malignant tumor abdominal metastasis with malignant ascites (or ascites exfoliative cytology confirmed malignant peritoneal effusion), without brain metastasis or liver metastasis. The patient had newly diagnosed abdominal metastasis with malignant ascites for no more than 1 month.
  • Progression on at least one line of prior standard therapy or unsuitability for standard systemic therapy.
  • No congestive heart failure, unstable angina pectoris, unstable arrhythmia within the past 6 months.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status: 0-3, and life expectancy 2 months or more.
  • No previous severe hematopoietic function, heart, lung, liver, kidney dysfunction and immunodeficiency.
  • One week before enrollment, the absolute value of peripheral blood T total lymphocytes ≥ 0.5 times the lower limit of normal, the absolute number of CD8 + T cells ≥ 200/uL, neutrophils ≥ 1.0 × 109/L; AST and ALT ≤ 3.0 times the upper limit of normal; creatinine ≤ 1.5 times the upper limit of normal or creatinine clearance ≥ 50 mL/min, serum albumin ≥ 30 g/L. After treatment, the indicators are allowed to reach the above criteria and last for 2 weeks. Transfusion therapy or granulocyte stimulating factor therapy is not allowed before treatment.
  • Patients must have the ability to understand and voluntarily sign an informed consent form.

Exclusion Criteria:

  • Pregnant or lactating women.
  • Patients with a history of other malignant diseases in the last 2 years, except cured skin cancer and carcinoma in situ.
  • Patients with a history of uncontrolled epilepsy, central nervous system diseases or mental disorders, whose clinical severity may hinder the signing of informed consent or affect the patient's compliance with drug treatment as judged by the investigator.
  • Clinically significant (ie, active) heart disease, such as symptomatic coronary heart disease, congestive heart failure New York Heart Association (NYHA) Class II or greater, or severe arrhythmia requiring drug intervention, or a history of myocardial infarction within the last 12 months.
  • Organ transplantation requiring immunosuppressive therapy.
  • Known active infection, or significant hematological, renal, metabolic, gastrointestinal, endocrine function or metabolic disorders, or other serious uncontrolled concomitant diseases as judged by the investigator.
  • Hypersensitivity to any component of the study drug.
  • History of immunodeficiency, including positive HIV test or other acquired, congenital immunodeficiency diseases, or a history of organ transplantation, or other related diseases requiring long-term oral hormone therapy (greater than 10 mg/d prednisone).
  • Patients who are in the period of acute and chronic tuberculosis infection (patients with positive T-spot test and suspicious tuberculosis lesions on chest radiography), are in the period of acute hepatitis infection or have chronic hepatitis B virus copy number higher than the normal range.
  • There are contraindications for abdominal paracentesis, including coagulation dysfunction such as severe thrombocytopenia, severe intestinal dilatation and enteroparalysis, and peritoneal adhesion.
  • Patients previously treated with immune checkpoint inhibitors and discontinued due to drug-related toxicity.
  • Other conditions considered unsuitable by the investigator.

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: PRaG combined PD-1 inhibitor intraperitoneal injection
PRaG(PD-1 inhibitor,Radiotherapy and GM-CSF) combined with PD-1 inhibitor intraperitoneal injection
Drug: Serplulimab
PD-1 inhibitor (HLX10, serplulimab) 100mg intraperitoneal infusion every two weeks after radiotherapy PD-1 inhibitor (HLX10, serplulimab) 3mg/kg intravenous infusion within one week after radiotherapy every two weeks
Other Names:
  • HLX10
Drug: Molgramostim
200ug qd subcutaneous injection for 7 days
Other Names:
  • rhGM-CSF
Radiation: Hypofractionated radiotherapy/Sterotactic body radiotherapy
8Gy*3f

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
Dose-limiting toxicity（DLT）by CTCAE5.0
Time Frame: 6 months (phase 1)
CTCAE is widely accepted throughout the oncology community as the standard classification and severity grading scale for adverse events in cancer therapy clinical trials and other oncology settings
6 months (phase 1)
Treatment Related Severe Adverse Effects
Time Frame: 6 months (phase 1)
Number of participants with treatment-related severe adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
6 months (phase 1)
OS
Time Frame: 12 months (phase 2)
overall survival time
12 months (phase 2)

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
OS
Time Frame: 12 months (phase 1)
overall survival time
12 months (phase 1)
PFS
Time Frame: 12 months (phase 1/2)
progression-free survival
12 months (phase 1/2)
ascites control rate
Time Frame: 12 months(phase 1/2 )
ascites control rate
12 months(phase 1/2 )

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.
Second Affiliated Hospital of Soochow 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 (Anticipated)

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, 2022

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 31, 2022

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.
September 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).
August 8, 2022

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 11, 2022

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 15, 2022

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 15, 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 11, 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

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.
  • JD-LK-2022-033-02

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

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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