Trial Title:
Low-dose Radiotherapy Combined With Conventional Fractionated Radiotherapy in Lung Cancer After Immunotherapy Resistance
NCT ID:
NCT05906329
Condition:
Cancer Patients
Conditions: Official terms:
Lung Neoplasms
Conditions: Keywords:
lung cancer, radiotherapy, immunotherapy resistance
Study type:
Interventional
Study phase:
N/A
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Radiation
Intervention name:
Low-dose radiotherapy combined with conventional fractionated radiotherapy
Description:
Select the primary lesion, the largest metastatic lesion, or the lesion causing symptoms,
and perform routine segmentation (1.8-2Gy/f, 40Gy-60Gy). For the remaining lesions, at
least one easily assessable and measurable lesion should be selected as the observation
lesion. Unselected lesions (≤ 10) should be given 1.6Gy/f, 1f/w, 4-6 times in total.
Arm group label:
Low-dose radiotherapy combined with conventional radiotherapy after immunotherapy resistance
Summary:
Pre-clinical and clinical studies have shown that low-dose radiation therapy has good
immune regulatory effects, activates different anti-tumor immune pathways, and regulates
tumor stroma to better promote T cell infiltration. Conventional fractionated
radiotherapy increases antigen release and presentation, and stimulates immune cells. In
theory, the combination of the two can reverse immune resistance. Our study aims to
clarify the efficacy and safety of low-dose radiotherapy combined with conventional
fractionated radiotherapy in reversing immune therapy resistance for patients with
non-small cell lung cancer, including objective response rate (ORR), progression free
survival time (PFS), disease control rate (DCR), health-related quality of life
assessment (HRQoL), and incidence of adverse events (AEs).
Detailed description:
This study is a researcher initiated, prospective, single arm, open clinical study.
Patients with non-small cell lung cancer who have undergone first-line or multi-line
immunotherapy and have no standard treatment option after resistance are recruited in
Department of Radiotherapy in the First Affiliated Hospital of Shandong First Medical
University. Patients who meet the conditions shall be treated after signing a written
informed consent form. Radiotherapy localization was performed through enhanced CT, and
the target area was delineated. The lesion included the primary lesion and lymph nodes
with a visible short diameter of ≥ 1cm, and there was metastasis confirmed by two deputy
chief physicians based on enhanced MR and PET/CT examination results.
The primary lesion, the largest metastatic lesion, or the lesion causing symptoms are
selected and performed conventional fractionated radiation of 1.8-2Gy/f, 40Gy-60Gy. For
the remaining lesions, at least one easily assessable and measurable lesion should be
selected as the observation lesion. Unselected lesions (≤ 10) should be given 1.6Gy/f,
1f/w, 4-6 times in total.
The immunotherapy regimen is implemented according to the specific dose and interval of
the original immunotherapy regimen, such as synchronous combination chemotherapy or anti
angiogenic drug therapy.
Immunotherapy is combined with radiotherapy at a frequency of once every 3 weeks until
progression.
The attending physician is responsible for developing personalized follow-up plans based
on the patient's personal situation, daily diagnosis and treatment routines, and
standards.
Evaluate the incidence of ORR, PFS, DCR, HRQoL, AE, and sAE according to the guidelines
for response criteria for use in trials testing immunotherapeutics (iRECIST) to evaluate
the patient's degree of benefit in this trial.
Regarding the determination of immunotherapy resistance, if the tumor does not respond to
initial immunotherapy and does not respond after more than 6 weeks of exposure to immune
drugs, primary resistance may occur and imaging is needed to confirm the disease
progression again. If two or more deputy chief physicians evaluate and determine the
disease progression, immunotherapy resistance may occur. On the other hand, if the drug
exposure time is more than 6 months, the tumor does not respond, and the acquired drug
resistance may occur, including the new drug-resistant mutant derived from the tumor and
the changes in the tumor microenvironment. The disease progress also needs to be re
determined by imaging. If the disease progress is determined after the evaluation of more
than two deputy chief physicians, the immunotherapy drug resistance occurs.
The quality control of all stages of clinical trials will be strictly implemented,
including relevant evaluation indicators, participants, and a complete management system
will be established.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
-
1. Patients are able to understand the informed consent form, voluntarily
participate and sign the informed consent form.
2. Age range from 18 to 65 years old, regardless of gender.
3. ECOG level 0-1; Expected life>6 months.
4. At least get into a liquid diet.
5. No history of severe allergies.
6. Hemoglobin ≥ 100 g/L, WBC ≥ 3.5 x10~9/L, neutrophils ≥ 1.8 x10~9/L, platelets ≥
10 x10~9/L; AST and ALT ≤ 2.5 × normal upper limit, AKP ≤ 2.5 × normal upper
limit.
7. Non small cell lung cancer (adenocarcinoma, large cell carcinoma, squamous
carcinoma, adenosquamous carcinoma, sarcomatoid carcinoma) confirmed by
cytology or histology.
8. Complete clinical data.
9. ≤ 10 primary and regional metastatic lymph nodes and distant metastatic
lesions, and ≤ 5 organ metastases.
10. Malignant tumor patients with immune therapy resistance (evaluated after 6-8
weeks of treatment and no improvement in clinical symptoms) without standard
treatment options.
11. There are measurable primary lesions, regional lymph node metastasis, and
distant metastatic lesions.
Exclusion Criteria:
-
1. Missing key patient information (pathological diagnosis, radiation dose,
imaging examination, previous treatment plans, etc.).
2. Refusal or lack of cooperation in research.
3. Patients who have participated in other clinical studies/trials within three
months.
4. Patients with brain metastases.
5. The researcher determines that there are any patients who are not suitable to
participate in the study.
6. Accompanied by severe infections.
7. Serious liver disease (such as cirrhosis), kidney disease, respiratory disease
or chronic system diseases such as uncontrollable diabetes and hypertension;
Patients who cannot tolerate radiation therapy.
8. Previous occurrence of immune related toxic side effects (immune myocarditis,
pneumonia, etc.).
9. Previous history of radiation therapy.
Gender:
All
Minimum age:
18 Years
Maximum age:
65 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
The First Affiliated Hospital of Shandong First Medical University (Qianfoshan Hospital)16766 Jingshi Road, Jinan City
Address:
City:
Jinan
Zip:
250013
Country:
China
Status:
Recruiting
Contact:
Last name:
JIANDONG ZHANG JD ZHANG, Dr.
Phone:
13583123486
Email:
zhangjd165@sina.com
Start date:
December 31, 2022
Completion date:
June 30, 2024
Lead sponsor:
Agency:
Qianfoshan Hospital
Agency class:
Other
Source:
Qianfoshan Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05906329
