Using radiation therapy for patients with remaining lung cancer after immunotherapy

An Open-label, Multicenter, Phase II Single Arm Trial of Stereotactic Body Radiotherapy for Oligo-residual Disease After Effective Treatment With PD-1/PD-L1 Inhibitors Among Metastatic Non-small Cell Lung Cancer

This study is testing if a special type of radiation therapy can help people with non-small cell lung cancer who still have some cancer left after immunotherapy.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 59 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Fudan University (Academic / other)
• Drugs / interventions: radiation
• Locations: 1 site (Shanghai)
• Trial ID: NCT04767009 on ClinicalTrials.gov

What this trial studies

This study evaluates the effectiveness and safety of stereotactic body radiation therapy (SBRT) in patients with oligometastatic non-small cell lung cancer (NSCLC) who have residual disease after treatment with PD-1/PD-L1 immune checkpoint inhibitors. The trial focuses on patients who have shown some response to immunotherapy but still have limited remaining cancer that can be targeted with radiation. Participants will receive SBRT following their initial treatment to assess if this approach can improve outcomes. The study aims to provide insights into managing advanced lung cancer more effectively.

Who should consider this trial

Good fit: Ideal candidates include adults with stage IV NSCLC who have oligometastatic disease and have previously been treated with PD-1/PD-L1 inhibitors.

Not a fit: Patients with extensive metastatic disease or those who have not received prior PD-1/PD-L1 inhibitors may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could enhance treatment options and outcomes for patients with advanced lung cancer who have not fully responded to immunotherapy.

How similar studies have performed: Other studies have shown promising results using SBRT in similar contexts, suggesting potential for success in this approach.

Eligibility criteria

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.
* Oligo-residual disease after effective treatment with PD-1/PD-L1 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.
* 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 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/PD-L1 inhibitors.

Where this trial is running

Shanghai

• Fudan University Shanghai Cancer Center — Shanghai, China (Recruiting)

Study contacts

• Principal investigator: Zhengfei Zhu, MD — Fudan University
• Study coordinator: Zhengfei Zhu, MD

Conditions NSCLC Stage IV