This pilot phase I trial aims to investigate the safety and tolerability of low dose radiotherapy (LDRT) and concurrent partial stereotactic body radiation therapy (SBRT) in combination with programmed cell death-1 (PD-1) inhibitors in Stage IV non-small cell lung cancer (NSCLC) patients who have failed standard therapy. At least 9 participants will be enrolled in this study. All will take part at West China Hospital, Sichuan University.
This exploratory phase I study will be conducted in West China Hospital, Sichuan University. A dose escalation of low dose radiotherapy (LDRT) and partial SBRT, 3 patients per cohort (a total of 9 patients) will be enrolled to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT). All eligible patients will receive LDRT + partial SBRT at different dose levels (decried as below), followed by PD-1 inhibitors starting within 7 days after radiation completed. PD-1 inhibitors will be given at doses as recommended in the instruction manual every 3 weeks until disease progression, unacceptable toxicities, the patient withdraws informed consent, or PD-1 inhibitors reaches a maximum of up to 48 months. Patients in the dose escalation will receive LDRT + partial SBRT at 3 cohorts with increasing dose levels: 2 Gy (2 Gy/f) + 10 Gy (10 Gy/f) in 1 fraction in dose level 1; 4 Gy (2 Gy/f) + 20 Gy (10 Gy/f) in 2 fractions in dose level 2; 6 Gy (2 Gy/f) + 30 Gy (10 Gy/f) in 3 fractions in dose level 3.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
9
LDRT at dose escalation levels: 2 Gy/1f, 4 Gy/2f, 6 Gy/3f with conventional external beam radiation.
Partial SBRT at dose escalation levels: 10 Gy/1f, 20 Gy/2f, 30 Gy/3f.
Patients will receive treatment with PD-1 inhibitor (dose as recommended in the instruction manual) every 3 weeks for a maximum of 48 months.
West China Hospital, Sichuan University
Chengdu, Sichuan, China
Number of participants with Adverse Events and/or Dose Limiting Toxicities as a Measurement of Safety and Tolerability of Low Dose Radiotherapy, Concurrent SBRT and PD-1 Inhibitors in Advanced NSCLC.
Time frame: 48 months
Progression Free Survival (PFS)
Investigator assessed PFS according to RECIST v1.1. Progression free survival is defined as time of enrollment to first evidence of progressive disease.
Time frame: up to 48 months after the enrollment
Overall Survival (OS)
OS is defined as the difference (in months) between the date of study enrollment to the date death due to any cause
Time frame: up to 48 months after the enrollment
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