Targeted high- and low-dose radiation with chemotherapy and immunotherapy for advanced lung cancer
A Single-centre Phase II Clinical Study of Spatially Fragmentation Radiotherapy Combined With Low-dose Radiotherapy for Reversal of Immunotherapy Combined With Chemotherapy Resistance in Locally Advanced Inoperable or Advanced Non-small Cell Lung Cancer
This trial tests whether adding focused high‑dose and low‑dose radiation to chemotherapy and immunotherapy helps people with advanced lung cancer whose disease progressed after prior immunotherapy.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 84 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Tianjin Medical University Cancer Institute and Hospital Academic / other |
| Drugs / interventions | immunotherapy, Chemotherapy |
| Locations | 1 site (Tianjin, Tianjin Municipality) |
| Trial ID | NCT06775678 on ClinicalTrials.gov |
What this trial studies
Adults with advanced lung cancer who progressed on prior immunotherapy are randomized 1:1 to an experimental arm receiving spatially fractionated radiation to a single lesion (high-dose region 800–1200 cGy ×3 fractions, low-dose regions 100–300 cGy ×5 fractions) plus low‑dose irradiation to other metastatic sites together with chemotherapy and immunotherapy, or to a control arm receiving conventional radiotherapy followed by chemo‑immunotherapy. Radiotherapy and systemic therapy are given during or within one week after radiotherapy, with serial blood immune monitoring and tumor biopsies taken before radiotherapy and after one cycle of immunotherapy to assess immune microenvironment changes. The trial records detailed toxicity and safety data and measures clinical efficacy outcomes in this phase II design. The aim is to see if the combined spatially fractionated and low‑dose radiation approach improves response and favorably alters immune markers compared with standard radiotherapy.
Who should consider this trial
Good fit: Adults with histologically confirmed lung cancer, a Karnofsky performance score ≥70, expected survival >3 months, lesions suitable for radiotherapy, and prior progression on immunotherapy are the intended participants.
Not a fit: Patients with lesions unsuitable for radiotherapy (for example malignant pleural effusion or meningeal metastasis), severe uncontrolled comorbidities, or an expected survival under three months are unlikely to benefit from this protocol.
Why it matters
Potential benefit: If successful, this approach could improve tumor control and help restore or enhance immunotherapy responses in patients whose lung cancer progressed after prior immunotherapy.
How similar studies have performed: This radiation approach is relatively novel; preclinical data and small clinical reports suggest immune‑modulating effects but there is no definitive large randomized evidence yet.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: 1. Sign the informed consent form. 2. Be at least 18 years old. 3. Have a Karnofsky Performance Status (KPS) score of 70 or higher and an expected survival of more than 3 months. 4. Have histopathological evidence of small cell lung cancer, lung adenocarcinoma, or lung squamous cell carcinoma. 5. Have received prior immunotherapy and experienced disease progression. 6. The site targeted for radiotherapy has not been previously irradiated or it has been at least 6 months since the last radiotherapy. Exclusion Criteria: 1. The patient has lesions that are not suitable for radiotherapy: malignant pleural effusion, ascites, meningeal metastasis, etc. 2. The patient has other serious comorbidities, such as myocardial infarction occurring within 6 months, severe arrhythmia, mental illness, etc., is unable to complete the treatment, or has an expected survival period of less than 3 months. 3. The patient has severe organ dysfunction, such as liver failure, cardiopulmonary failure, etc., and is difficult to tolerate radiotherapy. 4. The patient currently has a severe infection. 5. The patient has a known or suspected active autoimmune disease (congenital or acquired), such as uveitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, thyroiditis, etc. (Patients with vitiligo or those with cured childhood asthma can be included; patients with type 1 diabetes who have good insulin control can also be included). 6. The patient has experienced grade 3 or above cardiac or liver toxicity reactions or grade 4 toxicity reactions in other organs during previous immunotherapy. 7. Other situations where reviewers consider there are sufficient reasons for disqualification from the registered study: such as potential situations inconsistent with the clinical protocol.
Where this trial is running
Tianjin, Tianjin Municipality
- Tianjin Medical University Cancer Institute & Hospital — Tianjin, Tianjin Municipality, China (Recruiting)
Study contacts
- Study coordinator: Ningbo Liu, doctor
- Email: liuningbo@tjmuch.com
- Phone: +86 15602036608
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.