Clinical trial NCT06775678: Spatial Fragmentation Combined With Low-dose Radiotherapy for Immunotherapy Combined With Chemotherapy-resistant Locally Advanced or Advanced Non-small Cell Lung Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Lung Cancers
Radiation Treatment for Tumors
Keywords: Spatially Fractionated Radiation Treatment
low dose radiotherapy
Lung Cancers
Immunotherapy
Lead sponsor: Tianjin Medical University Cancer Institute and Hospital
Sponsor class: OTHER
First posted: 2025-01-15
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study was to evaluate the effect of immunotherapy combined with spatial fractionation radiotherapy and low dose radiotherapy on the prognosis of patients with advanced lung cancer under specific dose regimens (spatial fractionation radiotherapy: high dose region: 800-1200cGy × 3f, low dose region: 100-300cGy × 5f; low dose radiotherapy area: 100-300cGy × 5f). Through the phase II clinical trial, to determine the efficacy and safety of the combined treatment model in advanced lung cancer and its effect on the immune microenvironment of patients, so as to provide scientific basis for the optimization of treatment regimen for advanced lung cancer.

Detailed description: The eligible subjects were randomly divided into the experimental group and the control group according to the proportion of 1:1. The experimental group was treated with space fractionation radiotherapy for a single lesion, with a prescription dose of 800-1200cGy × 3f in the high-dose area and 100-300cGy × 5f in the low-dose area. All other irradiable metastatic foci were given low-dose radiotherapy (brain and bone metastases were given palliative radiotherapy according to clinical routine, but not within the range of low-dose radiotherapy). The prescription dose was 100-300cGy × 5f. Chemotherapy combined with immunotherapy was given during or within 1 week after radiotherapy. The control group only received conventional radiotherapy for chest or other lesions, followed by immunotherapy and chemotherapy according to the tumor stage, tolerance and genetic characteristics of the patients. Peripheral blood routine, immune cell (lymphocyte) subsets and related cytokines were detected before radiotherapy, on the day after radiotherapy and within 7 days after 1 cycle of immunotherapy. Before radiotherapy and after 1 cycle of immunotherapy, the metastatic focus was biopsied, fixed with 4% formaldehyde for 12-24 hours, dehydrated by gradient alcohol in the dehydrator, and finally embedded in paraffin to make wax blocks for preservation. The toxic and side effects of the treatment were recorded in detail, and the symptomatic treatment and detailed records can be made according to the severity. Patients with severe adverse reactions (SAE) will stop treatment and report to the research center for inclusion in the statistics. The toxicity and side effects were evaluated by CTCAE5.0 standard, and the long-term side effects were evaluated by RTOG long-term toxicity evaluation criteria.

Eligibility 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.

Primary outcomes:
measure: Objective response rate
timeFrame: From enrollment to the end of treatment at 6 mouths
Secondary outcomes:
measure: Disease control rate
timeFrame: From enrollment to the end of treatment at 6 mouths
measure: Progression free survival
timeFrame: From enrollment to the end of treatment at 6 mouths
measure: Overall survival
timeFrame: From enrollment to the end of treatment at 6 mouths
measure: Adverse Event
timeFrame: From enrollment to the end of treatment at 6 mouths
Other outcomes:
Locations:
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute & Hospital
state: Tianjin
Study officials:
References: