The goal of this prospective, single-arm exploratory clinical study is to explore the safty and efficacy of whole-brain radiotherapy combined with Thiotepa intrathecal injection combined with systemic therapy for the primary disease in the treatment of leptoeningeal metastases in solid tumors How works well was the combined therapy? How safe was combined therapy? Participants will continue systemic treatment, receive HA-WBRT combined with intrathecal injection of Thiotepa. Evaluate the efficacy and safety every 6 cycles. Researchers will evaluate whether this combination treatment is safe and whether it is more effective than previous studies.
Participants will receive a comprehensive treatment plan consisting mainly of HA-WBRT combined with intrathecal injection of Thiotepa. All eligible patients received intrathecal injection of Thiotepa twice a week for 1 week as induction treatment for 3 weeks, followed by once every week as consolidation therapy for 6 week and then once monthly as maintenance therapy, until progressive disease was observed or intolerance or adverse events (AEs) developed. The injection was administered by qualified individuals (certified personnel in the radiotherapy department of our hospital) . Thiotepa was injected 10mg each time, mixed with cerebrospinal fluid, and then injected slowly for 5-10 minutes. Evaluate the efficacy and safety every 6 cycles according to RANO-LM criteria.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
58
Participants will receive a comprehensive treatment plan consisting mainly of whole brain 30Gy/10F radiotherapy combined with intrathecal injection of Thiotepa. The injection was administered by qualified individuals (certified personnel in the radiotherapy department of our hospital). Thiotepa was injected 10mg each time, mixed with cerebrospinal fluid, and then injected slowly for 5-10 minutes.
The Second Affiliated Hospital of Zhejiang University
Hangzhou, Zhejiang, China
The objective response rate (ORR)
The proportion of responsive patients according to RANO-LM criteria
Time frame: 2 years
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
The primary safety analysis will be conducted based on subjects who experience toxicity (as defined by CTCAE standards). CTCAE version 5.0 will be used to evaluate safety through reported adverse events.
Time frame: 2 years
The disease control rate(DCR)
The proportion of patients who, according to RANO-LM criteria, achieve response and stable disease (SD) after treatment.
Time frame: 2 years
OS
overall survival
Time frame: 2 years
PFS
progression free survival
Time frame: 2 years
3-month OS
3-month overall survival
Time frame: 3 months
6-month OS
6-month overall survival
Time frame: 6 months
9-month OS
9-month overall survival
Time frame: 9 months
12-month OS
12-month overall survival
Time frame: 12 months
Mean total score on FACT-G
Quality of life (QOL) was evaluated as a secondary endpoint using the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire. The score of FACT-G will be compared before and after treatment. The FACT-G is a 27-item questionnaire that covers four HR-QOL sub-domains: physical, social, emotional, and functional well-being. Each of the questions will be scored on a scale from 0 (Not at all) to 4 (Very much) using a manual scoring template in which some items are reverse scored. The minimally important difference (MID) is 5 points for the FACT-G questionnaire. In other words, five points is the most minimal difference between the control group and treatment group scores that would indicate a clinically meaningful change. A positive change in points indicates better QOL.
Time frame: 2 year
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