Methotrexate Combined With Immunotherapy During Radiotherapy for Solid Tumors

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

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.

Study Overview

• Status: Recruiting
• Conditions: Solid Tumors
• Intervention / Treatment: Drug: Methotrexate tablets; Drug: Anti-PD-1 monoclonal antibody; Radiation: Radiotherapy

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Wei Geng, M.D.; Phone Number: 86-0515-66696967; Email: weihuo2001@163.com
• Study Contact Backup: Name: Bei Wang, Ph.D.; Phone Number: 86-0515-66696817; Email: yzwangbei@163.com

Study Locations

• China
  • Jiangsu
    • Yancheng, Jiangsu, China, 224000
      • Recruiting
      • Yancheng First People's Hospital
      • Contact: Wei Geng, M.D.; Phone Number: 86-0515-66696967; Email: weihuo2001@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subjects have unresectable/ metastatic solid tumors;
2. ≥ 18 years old;
3. Life expectancy of at least 3 months;
4. Eastern Cooperative Oncology Group performance status 0-2;
5. Have at least one measurable lesion ≥ 1 cm as defined by response criteria;
6. Adequate organ function.

Exclusion Criteria:

1. Subjects with a history of autoimmune diseases or syndromes;
2. Serious uncontrolled medical disorders or active infections;
3. Women who are pregnant or breastfeeding;
4. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: methotrexate+anti-PD-1 antibody+radiotherapy; Tablets with 5mg methotrexate are taken orally twice a week during radiotherapy. With anti-PD-1 monoclonal antibody, 200mg, Q3W.

Drug: Methotrexate tablets; Tablets with 5mg methotrexate are taken orally twice a week during the whole course of radiotherapy; Other Names: MTX; Drug: Anti-PD-1 monoclonal antibody; 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.; Other Names: PD-1 inhibitors; Radiation: Radiotherapy; 6～15MV X-ray, 2Gy/time, 5times/week. The duration of radiotherapy depends on the target lesion.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Yancheng First People's Hospital
• Investigators: Study Director: Wei Geng, M.D., Yancheng First People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2021
• Primary Completion (Anticipated): June 30, 2023
• Study Completion (Anticipated): December 31, 2024

Study Registration Dates

• First Submitted: August 28, 2022
• First Submitted That Met QC Criteria: August 30, 2022
• First Posted (Actual): August 31, 2022

Study Record Updates

• Last Update Posted (Actual): October 6, 2022
• Last Update Submitted That Met QC Criteria: October 3, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: anti-PD-1 monoclonal antibody, radiotherapy, methotrexate
• Additional Relevant MeSH Terms: Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Antibodies; Antibodies, Monoclonal; Methotrexate; Immune Checkpoint Inhibitors
• Other Study ID Numbers: 2021-K-099

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