Effect of Low-dose Radiotherapy on Tumor Immune Microenvironment in Oligometastases of NSCLC After Immunotherapy

Phase II Trial of Low-dose Radiotherapy (LDRT) Affecting the Tumor Immune Microenvironment (TME) in Oligometastasis, Oligoprogression, and Oligopersistence of Non-small Cell Lung Cancer (NSCLC) After Immunotherapy.

The purpose of this phase Ⅱ trial was to investigate the effect of low-dose radiotherapy (LDRT) on the tumor immune microenvironment (TME) in oligometastasis, oligoprogression, and oligopersistence of non-small cell lung cancer (NSCLC) after immunotherapy. At least 20 participants will be enrolled in this study. All will take part at Hetian District People's Hospital.

Study Overview

• Status: Withdrawn
• Conditions: Non-Small Cell Lung Cancer; Low-dose Radiotherapy; Tumor Microenvironment
• Intervention / Treatment: Radiation: low dose radiotherapy

Detailed Description

LDRT targeting oligometastases has been shown to enhance anti-tumour immunity by reprogramming the TME, thereby improving the efficacy of immunotherapy. The aim of this study was to collect pathological tissues from oligometastasis, oligoprogression, and oligopersistence of NSCLC after immunotherapy before LDRT (5Gy/5f) and up to 24h after LDRT in order to apply multiplexed fluorescence immunohistochemistry (mIHC) for evaluation of the tumor immune microenvironment. This study will be able to investigate the effect of LDRT on TME in oligometastatic lesions of NSCLC after immunotherapy and assess the efficacy and safety of LDRT.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Xinjiang Uygur Autonomous Region
    • Hetian, Xinjiang Uygur Autonomous Region, China, 848000
      • Hetian District People's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Agree to take pathologic biopsies of oligometastasis, oligoprogression, or oligopersistence lesions before and up to 24h after LDRT. And be willing and able to provide written informed consent/assent for the trial.
2. Patients with histologically or cytologically confirmed NSCLC.
3. Patient developed oligometastasis, oligoprogression or oligopersistence after standard immunotherapy.
4. Be ≥18 years of age on day of signing informed consent.
5. Be willing to undergo repeat biopsy of tumor lesions according to the study protocol.
6. Patients who have failed the standard therapy, or who are unsuitable for standard treatment, or refuse chemotherapy.
7. At least one measurable lesion according to RECIST 1.1. A lesion that has previously received radiotherapy can be considered a target lesion only if this lesion is clearly progressed after radiotherapy.
8. The target lesions (irradiated lesions) are > 5cm in in diameter
9. ECOG 0-2.
10. Life expectancy of > 3 months.
11. Patients must have normal organ and bone marrow function as defined below: Total bilirubin </= 1.5 x upper limit of normal (ULN). Aminotransferase (AST) Serum Glutamic Oxaloacetic Transaminase (SGOT)/ Alanine Aminotransferase (ALT) Serum Glutamic-Pyruvic Transaminase (SGPT) <2.5 X institutional upper limit of normal (</= 5 X institutional ULN for subjects with liver metastases) *WBC >/= 3500/uL, ANC >/= 1500/uL *Platelets >/= 90K/ul *Hemoglobin >/= 9g/dL *Creatinine </= 1.5 x ULN, or creatinine clearance ≥ 50 ml/min（Cockcroft-Gault equation）. Coagulation: International Normalized Ratio (INR)≤ 1.5 × ULN, Partial thromboplastin time (PTT) ≤1.5 × ULN; left ventricular ejection fraction (LVEF) >/= 50% and QTcF (Fridericia's formula) ≤ 450ms
12. Patients has recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
13. Wash out period for chemotherapy is more than ≥ 4 weeks, for targeted small molecule therapy ≥ 5 half-lives; palliative radiotherapy must have been completed for at least ≥ 2 weeks, chest radiotherapy must have been completed for at least ≥ 4 weeks, and major surgery must have been completed for ≥ 4 weeks.
14. Subjects with no severe pulmonary ventilation dysfunction, no acute heart failure, and no contraindication to radiotherapy as judged by the radiotherapist. Subjects who agree to receive immunotherapy and radiotherapy treatment.
15. Subjects should agree to use an adequate method of contraception.

Exclusion Criteria:

1. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis and/or spinal cord compression, etc.
2. With oncologic emergencies that require immediate treatment
3. EGFR/ALK/ROS-1 mutation or mutation status unknown.
4. Has evidence of interstitial lung disease or active and/or non-infectious pneumonitis (drug-induced pneumonia, radiation-induced pneumonia, etc.) requiring steroid therapy.
5. History of pulmonary fibrosis, pulmonary hypertension, severe irreversible airway obstruction disease
6. Patients with peripheral neuropathy.
7. Significant heart disease or impairment of cardiac function
8. Fluid accumulating in the third space, such as pericardial effusion, pleural effusion and peritoneal effusion that remains uncontrolled by aspiration or other treatment
9. Known allergy to drugs or excipients, known severe allergic reaction to any of the PD-1 monoclonal antibodies
10. Severe infection within 4 weeks prior to the start of study treatment, including but not limited to hospitalization for infection, bacteremia, or severe pneumonia; treatment with oral or intravenous antibiotics within 2 weeks prior to the start of study treatment; patients receiving prophylactic antibiotic therapy (e.g., to prevent urinary tract infection or exacerbation of COPD) are eligible for this study.
11. Known or suspected active autoimmune disease (congenital or acquired) such as uveitis, enterocolitis, hepatitis, pituitary inflammation, vasculitis, nephritis, thyroiditis, etc. (patients with vitiligo, or resolved childhood asthma may be enrolled; patients with type I diabetes with good insulin control may also be enrolled)
12. Known allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• 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: Experimental arm; Experimental: LDRT on oligometastasis, oligoprogression, and oligopersistence of NSCLC after immunotherapy; LDRT: Patient undergoes LDRT using a medical linear gas pedal (5Gy/5f); Biopsy: Collect pathological tissues from oligometastasis, oligoprogression, and oligopersistence of NSCLC after immunotherapy before LDRT (5Gy/5f) and up to 24h after LDRT	Radiation: low dose radiotherapy; LDRT (5Gy/5f) of oligometastasis, oligoprogression, and oligopersistence of NSCLC after immunotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Analysis of the tumor immune microenvironment	mIHC: Multiplex fluorescence immunohistochemical analysis was performed on the collected pathological tissue samples(before LDRT (5Gy/5f) and up to 24h after LDRT) using equipment such as fluorescence microscope and flow cytometer. To reveal the effect of LDRT on the tumor immune microenvironment by detecting the expression of different immune markers.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with Adverse Events and/or Dose Limiting Toxicities as a Measurement of Safety and Tolerability of Low Dose Radiotherapy	Number of participants with Adverse Events and/or Dose Limiting Toxicities as a Measurement of Safety and Tolerability of Low Dose Radiotherapy	48 months
Progression Free Survival (PFS)	Investigator assessed PFS according to RECIST v1.1. Progression free survival is defined as time of enrollment to first evidence of progressive disease up to 48 months after the enrollment	48 months
Overall Survival (OS)	OS is defined as the difference (in months) between the date of study enrollment to the date death due to any cause up to 48 months after the enrollment	48 months

Collaborators and Investigators

• Sponsor: Hetian District People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 18, 2024
• Primary Completion (Estimated): March 18, 2025
• Study Completion (Estimated): March 18, 2026

Study Registration Dates

• First Submitted: March 19, 2024
• First Submitted That Met QC Criteria: March 19, 2024
• First Posted (Actual): March 26, 2024

Study Record Updates

• Last Update Posted (Actual): April 25, 2024
• Last Update Submitted That Met QC Criteria: April 23, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: KY-2024004

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