SBRT for Oligo-residual and Oligoprogressive NSCLC After Treatment With PD-1 Immune Checkpoint Inhibitors

An Open-label, Multicenter, Phase II Single Arm Trial of Stereotactic Body Radiotherapy for Oligo-residual and Oligoprogressive NSCLC After Treatment With PD-1 Immune Checkpoint Inhibitors

Despite the impressive response rate to PD-1 immune checkpoint inhibitors, resistance inevitably develops in most patients. Stereotactic body radiation therapy (SBRT) plays a growing role in the management of oligometastatic disease. This study aims to evaluate the efficacy and safety of SBRT for oligo-residual or oligoprogressive NSCLC after treatment with PD-1 inhibitors.

Study Overview

• Status: Recruiting
• Conditions: NSCLC Stage IV
• Intervention / Treatment: Drug: PD-1 Blockade; Radiation: SBRT

• Study Type: Interventional
• Enrollment (Estimated): 59
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Zhengfei Zhu, MD; Phone Number: +86-18017312901; Email: fuscczzf@163.com
• Study Contact Backup: Name: Jianjiao Ni, MD; Phone Number: 13761974092; Email: nijianjiao8@sina.com

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • Fudan University Shanghai Cancer Center
    • Contact: Zhengfei Zhu, MD; Phone Number: +86-18017312901; Email: fuscczzf@163.com
    • Contact: Jianjiao Ni, MD; Phone Number: 13761974092; Email: nijianjiao8@sina.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age at least 18 years.
• ECOG PS 0-1.
• Patients with pathologically confirmed stage IV NSCLC by tumor biopsy and/or fine-needle aspiration.
• Negative for driver genes including EGFR, ALK, and ROS-1.
• Progressive disease or oligo-residual disease after treatment with PD-1 inhibitors that would be amenable to SBRT in the opinion of the investigator.
• Patients with brain metastasis are eligible if they are asymptomatic, neurologically stable, and off corticosteroids.

• Patients with a history of radiotherapy are eligible if they satisfy the following criteria:

  1. Radiotherapy administered more than 4 weeks before study entry.
  2. At least one measurable lesion outside the radiation field.
  3. Progressing, previously non-irradiated lesions amenable to SBRT.
• Patients with no indications for palliative radiotherapy in the opinion of the investigator.
• Patients with a prior history of surgery are eligible if they have sufficiently recovered from the toxicity and/or complications of surgery.
• Signed informed consent for the use of fresh tumor biopsies before and during the treatment.
• Women of childbearing age and men must agree to use effective contraception during the trial.
• Life expectancy of more than 3 months.

• Adequate organ function within 1 week prior to enrollment:

  1. Adequate bone marrow function: hemoglobin ≥80g/L, white blood cell (WBC) count ≥ 4.0 * 10 ^ 9/L or neutrophil count ≥ 1.5 * 10 ^ 9/L, and platelet count ≥ 100 * 10 ^ 9/L;
  2. Adequate hepatic function: total bilirubin < 1.5 x upper limit of normal (ULN). Note: If total bilirubin is > 1.5 x ULN, direct bilirubin must ≤ ULN, Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤2.5 ULN;
  3. Adequate renal function: serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 50 mL/min;
• Ability to understand and willingness to provide the informed consent.

Exclusion Criteria:

• Severe autoimmune disease: inflammatory bowel disease (including Crohn's disease and ulcerative colitis), rheumatoid arthritis, scleroderma, systemic lupus erythematosus, Wegener's granulomatosis and related vasculitides.
• Symptomatic interstitial lung disease or clinically active infectious/non-infectious pneumonitis.
• History of another malignancy or concurrent malignancy.
• Active infection, congestive heart failure, or any evidence of myocardial infarction, unstable angina pectoris or cardiac arrhythmia within 6 months prior to enrollment.
• Any evidence of severe or uncontrolled systemic diseases, which in the investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol. Screening for chronic conditions is not required.
• Patients in whom palliative radiotherapy is indicated in the opinion of the investigator.
• Mixed small cell with non-small cell lung cancer histology.
• The patient is pregnant (confirmed by serum b-HCG if applicable) or is breastfeeding.
• Patients who have received tumor vaccine; or administration of live, attenuated vaccine within 4 weeks before the start of treatment. Note: Influenza vaccination is permitted only during influenza season, while live, attenuated influenza vaccine such as FluMist is not allowed.
• Patients receiving concurrent chemotherapy drugs, immunosuppressive agents, or other investigational treatment. Long-term corticosteroid users are also excluded.
• Mental disorders, drug abuse, and social condition that may negatively impact compliance in the investigator's opinion.
• Prior allergic reaction or contraindications to PD-1 blockade.

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: SBRT for oligoprogressive NSCLC

Drug: PD-1 Blockade; Patients will receive PD-1 blockade for up to 2 years or until confirmed progression or unacceptable toxicity. PD-1 blockade will be administrated as an intravenous(IV) infusion.; Radiation: SBRT; Patients with oligo-residual or oligoprogressive NSCLC after treatment with PD-1 inhibitors will be treated with curative-intent SBRT of progressing lesions. The choice of dose-fractionation regimen is at the discretion of the treating radiation oncologist. PD-1 blockade will be withheld one day before the treatment and resumed within 2 weeks after completion of SBRT.; Other Names: Stereotactic body radiation therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	PFS was measured from the date of the initiation of anti-PD-1 therapy to the date of disease progression as defined by Response Evaluation Criteria in Solid Tumor (RECIST) Version 1.1 or death	Two years
Percentage of Participants With Adverse Events	Treatment-related adverse events were assessed and graded according to CTCAE v. 5.0.without the appearance of any new metastatic lesions outside the radiation field for at least 1 year after the start of SBRT. Patients who died or developed progressive disease within the radiation field within 1 year after SBRT were censored.	Two year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	OS was defined as the time from the date of enrollment until death by any cause. Participants still alive at the time of data analysis were censored at the date of last follow-up.	Two years

Collaborators and Investigators

• Sponsor: Fudan University
• Investigators: Principal Investigator: Zhengfei Zhu, MD, Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2021
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: February 19, 2021
• First Submitted That Met QC Criteria: February 19, 2021
• First Posted (Actual): February 23, 2021

Study Record Updates

• Last Update Posted (Actual): July 11, 2023
• Last Update Submitted That Met QC Criteria: July 10, 2023
• Last Verified: July 1, 2023

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: 2020-NSCLCSBRT-2

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No