Hypofractionated Radiotherapy Combined With PD-1 Inhibitor Sequential GM-CSF and IL-2 for the Treatment of Advanced Refractory Solid Tumors (PRaG2.0)

Study Overview
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Brief Summary
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This is a prospective multicenter clinical study to determine the efficacy and safety of hypofractionated radiotherapy combined with PD-1 inhibitor sequential GM-CSF and IL-2 for advanced multiple metastatic solid tumors

Official Title
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A Prospective Multicenter Clinical Study of Hypofractionated Radiotherapy Combined With PD-1 Inhibitor Sequential GM-CSF and IL-2 for the Treatment of Advanced Refractory Solid Tumors

Conditions
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Advanced Refractory Solid Tumors

Intervention / Treatment
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* Radiation: Hypofractionated radiotherapy
* Drug: PD-1 inhibitor
* Drug: GM-CSF
* Drug: IL-2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years. The enrolled patients meet the recurrence or metastasis of advanced solid malignant tumors, have a clear pathological diagnosis report or medical history, the guidelines do not clearly recommend standard treatment plans or cannot tolerate standard treatment plans, and have clear measurable metastatic lesions (>1cm); No congestive heart failure, unstable angina, or unstable arrhythmia occurred in the past 6 months. The patient's activity status score is 0-3 points based on the Eastern Cooperative Oncology Group (ECOG) scoring method, and the life expectancy assessment is ≥3 months. No serious hematopoietic function, abnormal heart, lung, liver, kidney function and immune deficiency in the past. One week before admission, the absolute value of T lymphocytes was ≥0.5 times the lower limit of normal, and neutrophils ≥1.0×109/L; AST and ALT were ≤3.0 times the upper limit of normal (for liver cancer/liver metastasis ≤5.0 times) Upper limit of normal); creatinine ≤3.0 times the upper limit of normal. The patient have the ability to understand and voluntarily sign an informed consent form. Exclusion Criteria: Pregnant or breastfeeding women. Those with a history of other malignant diseases in the last 5 years, except for cured skin cancer and cervical carcinoma in situ. If there is a history of uncontrolled epilepsy, central nervous system disease or mental disorder, the investigator's judgment of its clinical severity may hinder the signing of informed consent or affect the patient's compliance with medication. Clinically serious (ie active) heart disease, such as symptomatic coronary heart disease, New York Heart Association (NYHA) grade II or more severe congestive heart failure, or severe arrhythmia requiring drug intervention, or recent A history of myocardial infarction within 12 months. Those who need immunosuppressive therapy for organ transplantation. A known major active infection, or the researcher's judgment has major blood, kidney, metabolism, gastrointestinal, endocrine function or metabolic disorders, or other serious uncontrolled accompanying diseases. Those who are allergic to any research drug ingredients. A history of immunodeficiency, including HIV positive or other acquired or congenital immunodeficiency diseases, or a history of organ transplantation, or those with other immune-related diseases that require long-term oral hormone therapy. In the period of acute and chronic tuberculosis infection (T-spot test is positive, patients with suspected tuberculosis foci on chest X-ray). Other situations that the researcher thinks are not suitable for inclusion in the group.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RT+PD-1+GM-CSF+IL-2<br> | Radiation: Hypofractionated radiotherapy<br>* 10-24Gy/5-8Gy/2-3f<br>Drug: PD-1 inhibitor<br>* q3w, until PD<br>Drug: GM-CSF<br>* 200μg, D1-D7, ≥8 cycles<br>Drug: IL-2<br>* at a dose of 2 million IU, D8-D14, ≥8 cycles<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression free survival，PFS | Time from cycle 1, day 1 of treatment to disease progression or death due to any cause | Up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate，ORR | The proportion of patients with at least one tumor scan of complete response (CR) or partial response (PR) using RECIST v1.1. | Up to 3 years | 
| Disease control rate，DCR | The proportion of patients with at least one tumor scan of complete response (CR) or partial response (PR) or stable disease (SD) using RECIST v1.1. | Up to 3 years | 
| Overall survival，OS | Time from cycle 1, day 1 of treatment until death due to any cause | Up to 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hypofractionated radiotherapy, PD-1 inhibitor, GM-CSF, IL-2