Abscopal Effect From the Low-dose Radiotherapy in Polymetastatic Cancer Patients Receiving Stereotactic Radiotherapy

Study Overview
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Brief Summary
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Recently, MD Anderson Cancer Center reported the phase II trial to investigate high-dose radiotherapy (HDRT, 20-70 Gy) and low-dose radiotherapy (LDRT, 1-10 Gy) for metastatic cancer patients who had undergone immunotherapy. HDRT or HDRT+LDRT was conducted in two respective groups and the treatment group was determined according to the disease status of participants, not randomization. Immunotherapy was maintained in this clinical study. Therefore, we aim to investigate this abscopal effect from adding LDRT to HDRT, irrespective of previous immunotherapy, in this multicenter, single-arm study.

Official Title
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Abscopal Effect From the Addition of Low-dose Radiotherapy in Polymetastatic Cancer Patients Receiving Stereotactic Radiotherapy: a Multicenter, Single-arm Clinical Study (KROG 22-11)

Conditions
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Neoplasms, Secondary Malignant Neoplasm

Intervention / Treatment
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* Radiation: SBRT + LDRT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who can provide their written informed consent Age ≥19 years Patients with histologically confirmed primary solid (irrespective of the status of the primary tumor) Patients with ECOG performance status 0-2 Patients planning stereotactic body radiotherapy (three fractions) for extracranial metastases Based on RECIST v1.1, patients with at least one extracranial measurable lesion other than SBRT lesions Patients with one or more measurable lesions, which are not suitable for SBRT or palliative radiotherapy and can be considered for LDRT (bone metastasis is not indicated for LDRT) Patients with hematologic function suitable for radiotherapy (absolute neutrophil count ≥1,500/mm^3, hemoglobin ≥9 g/dL, platelet count ≥100,000/mm^3) Patients with a life expectancy of 6 months or more according to the researcher's judgment Exclusion Criteria: Patients participating in other clinical studies that may affect the efficacy/safety of this clinical study Patients with brain metastasis Patients planning SBRT for all measurable lesions due to oligometastasis Patients with a history of radiotherapy for extracranial metastases within 3 months of the enrollment Patients unable to cooperate with stereotactic body radiotherapy Patients who are pregnant or planning to Patients with advanced or multiple malignancies requiring aggressive treatment (excluding skin cancers other than melanoma or intraepithelial cancer) Patients who have received systemic steroid therapy or immunosuppressive therapy within 2 weeks of enrollment - Patients with an (e.g. allergic disease, radiation pneumonitis, etc.) active autoimmune disease requiring systemic treatment within the past 2 years, evidence of clinically severe autoimmune disease, or syndrome requiring systemic steroid or immunosuppressive therapy (Patients who need intermittent use of bronchodilators, inhaled steroids, or topical steroid injections, hypothyroid patients on stable hormone replacement therapy, type 1 diabetes patients, or patients recovering from childhood asthma/atopic dermatitis are permitted) Patients with active infection requiring systemic treatment

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SBRT + LDRT<br> | Radiation: SBRT + LDRT<br>* Stereotactic body radiotherapy (SBRT) and low-dose radiotherapy (LDRT) are administered concurrently. SBRT is administered three times, at intervals of 1-2 days, and patients are treated with LDRT along with SBRT. LDRT is planned to irradiate EQD2 6 Gy considering the scattered dose caused by SBRT.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Abscopal effect rate of low-dose radiotherapy lesions | The proportion of patients with an abscopal response of low-dose radiotherapy lesions assessed by RECIST v1.1 | 3 months after completion of radiotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Abscopal effect rate of low-dose radiotherapy lesions | The proportion of patients with an abscopal response of low-dose radiotherapy lesions assessed by RECIST v1.1 | 1, 6, and 12 months after completion of radiotherapy | 
| Overall response rate | The proportion of patients showing complete or partial response of metastatic lesions | 1, 3, 6, and 12 months after completion of radiotherapy | 
| Progression-free survival rate | From the date of enrollment to the date of progression or death assessed by RECIST v1.1 | 12 months after completion of radiotherapy | 
| Overall survival rate | From the date of enrollment to the date of death or last follow-up assessed by RECIST v1.1 | 12 months after completion of radiotherapy | 
| Adverse event | The proportion of patients with treatment-related adverse events as assessed by CTCAE v5.0 | 12 months after completion of radiotherapy | 
| Immune cell subsets of peripheral blood and tissue samples | Number of immune cell count | 1 and 3 months after completion of radiotherapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neoplasm Metastasis