Methotrexate Combined With Immunotherapy During Radiotherapy for Solid Tumors

Study Overview
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Brief Summary
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Immune checkpoint inhibitors, such as programmed death 1 (PD-1) and programmed cell death-Ligand 1 (PD-L1), offer new approaches for systemic treatment of tumors, but clinical efficacy remains limited. Previous studies by our team have found that methotrexate can activate anti-tumor immunity. The discovery of a new effect of this drug will improve tumor response to immunotherapy and prognosis of patients.

Detailed Description
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Malignant tumor is a systemic and complex disease that seriously endangers human health, surgery is the preferred treatment for solid tumors. Due to the extensive invasion and metastasis of advanced tumors, radiotherapy and chemotherapy are the main treatment options. However, the tolerance of tumor to chemoradiotherapy often leads to treatment failure and poor prognosis. Immunotherapy provides a new approach for the systemic treatment of tumors, but the clinical efficacy is still limited. Therefore, it is important to find effective drugs to improve the tumor response to radiotherapy and immunotherapy. Previous studies by our team have found that methotrexate can activate anti-tumor immunity. The discovery of a new effect of this drug will improve tumor response to immunotherapy and prognosis of patients. The objective of this clinical trial is to explore the efficacy and safety of methotrexate combined with immunotherapy and radiotherapy in patients with unresectable/recurrence solid tumors.

Official Title
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Safety and Efficacy of Oral Methotrexate Tablets Combined With Immunotherapy During Radiotherapy for Unresectable/Metastatic Solid Tumors: a Single-center, Prospective Study

Conditions
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Solid Tumors

Intervention / Treatment
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* Drug: Methotrexate tablets
* Drug: Anti-PD-1 monoclonal antibody
* Radiation: Radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects have unresectable/ metastatic solid tumors; ≥ 18 years old; Life expectancy of at least 3 months; Eastern Cooperative Oncology Group performance status 0-2; Have at least one measurable lesion ≥ 1 cm as defined by response criteria; Adequate organ function. Exclusion Criteria: Subjects with a history of autoimmune diseases or syndromes; Serious uncontrolled medical disorders or active infections; Women who are pregnant or breastfeeding; Subjects have other factors that may cause them to terminate the study, such as other serious medical conditions (including mental illness) that require combined treatment.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: methotrexate+anti-PD-1 antibody+radiotherapy<br>Tablets with 5mg methotrexate are taken orally twice a week during radiotherapy. With anti-PD-1 monoclonal antibody, 200mg, Q3W. | Drug: Methotrexate tablets<br>* Tablets with 5mg methotrexate are taken orally twice a week during the whole course of radiotherapy<br>* Other names: MTX;Drug: Anti-PD-1 monoclonal antibody<br>* Anti-PD-1 monoclonal antibody 200mg is given intravenously every 3 weeks from the first day of radiotherapy until or after the end of treatment.<br>* Other names: PD-1 inhibitors;Radiation: Radiotherapy<br>* 6～15MV X-ray, 2Gy/time, 5times/week. The duration of radiotherapy depends on the target lesion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | ORR is defined as the percentage of participants in the analysis population who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) | Up to 3 months | 
| Treatment-related adverse events (AEs) | Incidence, nature, and severity of adverse events graded according to the NCI CTCAE v5.0 | Up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Numbers of CD3+, CD4+ and CD8+T lymphocyte subsets in peripheral blood detected by flow cytometry | Laboratory tests for T-cell detection will be performed before and after treatment. | Approximately 2 months | 
| Levels of IL-6, TNF-α and IFN-γ in peripheral blood detected by flow cytometry | Peripheral blood will be collected before, during and after treatment for laboratory serum cytokine detection. | Approximately 2 months | 
| Progression-free Survival (PFS) per RECIST 1.1 | PFS is defined as the time from enrollment to the first documented disease progression per RECIST 1.1 based on blinded independent central review or death due to any cause, whichever occurs first. | Up to 12 months | 
| Overall Survival (OS) | OS is defined as the time from enrollment to death from any cause during the course of the study. | Up to 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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anti-PD-1 monoclonal antibody, radiotherapy, methotrexate