Solid Tumor Leptomeningeal MetastasisPhase 2NCT06376292
A Prospective Single Arm Phase II Exploratory Study on the Combination of Whole Brain Radiotherapy, Thiotepa Intrathecal Injection and Systemic Treatment of Primary Diseases in the Treatment of Solid Tumor Leptomeningeal Metastasis
A Phase 2 study testing Intrathecal Injection of Thiotepa+Radiation+Systemic Treatment of Primary Diseases in people with Solid Tumor Leptomeningeal Metastasis, run by Second Affiliated Hospital, Zhejiang University, School of Medicine at 1 site in China.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Solid Tumor Leptomeningeal Metastasis
- What is being tested?
- Intrathecal Injection of Thiotepa+Radiation+Systemic Treatment of Primary Diseases
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 58 participants
- Where
- 1 siteChina
- Study dates
- 6 Jan 2024to 1 Sep 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1) Voluntary participation in clinical research: fully understand and be informed of this study, and sign an informed consent form in writing; Willing to follow and capable of completing all experimental procedures.
- 2) Age: ≥ 18 years old, both male and female. 3) Solid tumor patients diagnosed with meningeal metastasis according to the EANO-ESMO guidelines 4) Whole brain 6MX X-ray PTV D95/30Gy/10F regimen radiotherapy has been performed 5) CNS IPI ≥ 4. 6) An increase in serum LDH or involvement of more than one extranodal site. 7) ECOG score ≤ 2. 8) Expected survival time is at least 3 months. 9) Adequate organ and bone marrow function, without severe hematopoietic dysfunction, heart, lung, liver, kidney dysfunction, and immune deficiency (no blood transfusion, granulocyte colony-stimulating factor, or other related medical support received within 14 days prior to the use of the study drug):
- Blood routine: Absolute neutrophil count (ANC) ≥ 1.5'109/L (1500/mm3), platelet count ≥ 75'109/L, hemoglobin count ≥ 9 g/dL (if bone marrow is involved, platelet count ≥ 50'109/L, ANC ≥ 1.0'109/L, hemoglobin count ≥ 8 g/dL).
- Liver function: Serum bilirubin ≤ 1.5 times the upper limit of normal value, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 1.5 times the upper limit of normal value (if liver involvement occurs, AST is allowed, ALT ≤ 5 times the upper limit of normal value).
- Renal function: Serum creatinine ≤ 1.5 times the upper limit of normal value.
- Coagulation function: INR ≤ 1.5 times the upper limit of normal value; PT and APTT ≤ 1.5 times the upper limit of normal values (unless the subject is receiving anticoagulant treatment and PT and APTT are within the expected range of anticoagulant treatment during screening).
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- 10) Left ventricular ejection fraction (LVEF) ≥ 50% in cardiac function examination.
- 11) The serum pregnancy test is negative, and effective contraceptive measures are taken within 6 months from the signing of the informed consent form until the use of the last chemotherapy.
- 12) Thyroid stimulating hormone (TSH), free thyroxine (FT4), or free triiodothyronine (FT3) are all within the normal range of ± 10%.
- 13) Ophthalmic examination: including dilated pupil fundus examination, slit lamp examination, and fundus color photography.
Who cannot join
- 1) Participating in other clinical studies, or the first study drug administration is less than 4 weeks after the end of the previous clinical study treatment.
- 2) Has suffered from other malignant tumors within the past 5 years. 3) Patients who have received CNS guided treatment and prevention. 4) Patients with a known history of human immunodeficiency virus (HIV) infection and/or acquired immunodeficiency syndrome.
- 5) Patients with active autoimmune diseases or a history of hematological autoimmune diseases with a high risk of recurrence, including but not limited to immune related neuropathy, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain's syndrome, myasthenia gravis, systemic lupus erythematosus, connective tissue disease, scleroderma, inflammatory bowel cancer (including Crohn's disease and ulcerative colitis), autoimmune hepatitis Toxic epidermal necrolysis or Stevens Johnson syndrome.
- 6) Patients with active chronic hepatitis B or active hepatitis C. Patients with positive hepatitis B B surface antigen or hepatitis C virus antibody in screening period must further pass the hepatitis B virus DNA drop test (not more than 1000 iu/ml) and HCV RNA test (not more than the lower limit of the test method), and can be included in the test only after the active hepatitis B or hepatitis C infection requiring treatment is excluded. Hepatitis B virus carriers, hepatitis B patients who are stable after drug treatment and cured hepatitis C patients can be included in the group.
- 7) Suffer from active pulmonary tuberculosis. 8) Currently, there is interstitial lung disease or infectious pneumonia. 9) Active infections that require systematic anti infective treatment, including but not limited to bacterial, fungal, or viral infections.
- 10) Screening for heart failure classified as Grade III or IV according to the New York Heart Association (NYHA) functional classification within the first 6 months, unstable angina, severe uncontrolled ventricular arrhythmias, and electrocardiograms showing acute ischemia or myocardial infarction.
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- 11) QTcF interval>480msec, unless secondary to bundle branch block. 12) Suffering from uncontrollable comorbidities, including but not limited to uncontrollable hypertension, active peptic ulcers, or hemorrhagic diseases.
- 13) Individuals with a history of mental illness; Individuals with no or limited capacity for behavior.
- 14) According to the researchers, the patient's underlying condition may increase their risk of receiving treatment with the investigational drug, or may cause confusion regarding the occurrence of toxic reactions and their judgment.
- 15) Other researchers believe that patients who are not suitable to participate in this study.
Trial locations and contacts
1 site in 1 country.
China1 site
The Second Affiliated Hospital of Zhejiang University
Hangzhou, Zhejiang, 310000
About this study
Official title: A Prospective Single Arm Phase II Exploratory Study on the Combination of Whole Brain Radiotherapy and Thiotepa Intrathecal Injection for Systemic Treatment of Primary Diseases in the Treatment of Solid Tumor Leptomeningeal Metastasis
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.
Read the detailed description
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.
- Conditions
- Solid Tumor Leptomeningeal Metastasis
- Being tested
- Intrathecal Injection of Thiotepa+Radiation+Systemic Treatment of Primary Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intrathecal Injection of Thiotepa+Radiation+Systemic Treatment of Primary DiseasesDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Interventional arm | Experimental | Participants will receive a comprehensive treatment plan consisting mainly of whole brain 30Gy/10F radiotherapy combined with intrathecal injection of Thiotepa twice a week for a total of 4 weeks. Receives: Drug: Intrathecal Injection of Thiotepa+Radiation+Systemic Treatment of Primary Diseases |
What is being measured
The primary outcome is the main question the study is designed to answer.
The objective response rate (ORR)
The proportion of responsive patients according to RANO-LM criteria
Measured: 2 years
Secondary outcomes (9)
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.
Measured: 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.
Measured: 2 years
OS
overall survival
Measured: 2 years
PFS
progression free survival
Measured: 2 years
3-month OS
3-month overall survival
Measured: 3 months
6-month OS
6-month overall survival
Measured: 6 months
9-month OS
9-month overall survival
Measured: 9 months
12-month OS
12-month overall survival
Measured: 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.
Measured: 2 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Apr 2024
- Study start6 Jan 2024
- Primary completion1 Sep 2025
- Study completion1 Sep 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Solid Tumor Leptomeningeal MetastasisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 58 participants (actual)
Sponsor and investigators
- Lead sponsor
- Second Affiliated Hospital, Zhejiang University, School of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06376292
- Sponsor's protocol ID
- Y2024-0106
- Status last verified
- Dec 2025
- First submitted
- 27 Feb 2024
- Last updated
- 18 May 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective Single Arm Phase II Exploratory Study on the Combination of Whole Brain Radiotherapy and Thiotepa Intrathecal Injection for Systemic Treatment of Primary Diseases in the Treatment of Solid Tumor Leptomeningeal Metastasis
- ClinicalTrials.gov ID
- NCT06376292
- Acronym / sponsor ID
- Y2024-0106
- Conditions
- Solid Tumor Leptomeningeal Metastasis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 58 participants (actual)
- Lead sponsor
- Second Affiliated Hospital, Zhejiang University, School of MedicineUniversity, hospital or other
- Study start
- 6 Jan 2024 (actual)
- Primary completion
- 1 Sep 2025 (actual)
- Study completion
- 1 Sep 2025 (actual)
- First posted
- 19 Apr 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Interventional arm | Experimental | Drug: Intrathecal Injection of Thiotepa+Radiation+Systemic Treatment of Primary DiseasesParticipants will receive a comprehensive treatment plan consisting mainly of whole brain 30Gy/10F radiotherapy combined with intrathecal injection of Thiotepa twice a week for a total of 4 weeks. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 1) Voluntary participation in clinical research: fully understand and be informed of this study, and sign an informed consent form in writing; Willing to follow and capable of completing all experimental procedures.
- 2) Age: ≥ 18 years old, both male and female. 3) Solid tumor patients diagnosed with meningeal metastasis according to the EANO-ESMO guidelines 4) Whole brain 6MX X-ray PTV D95/30Gy/10F regimen radiotherapy has been performed 5) CNS IPI ≥ 4. 6) An increase in serum LDH or involvement of more than one extranodal site. 7) ECOG score ≤ 2. 8) Expected survival time is at least 3 months. 9) Adequate organ and bone marrow function, without severe hematopoietic dysfunction, heart, lung, liver, kidney dysfunction, and immune deficiency (no blood transfusion, granulocyte colony-stimulating factor, or other related medical support received within 14 days prior to the use of the study drug):
- 10) Left ventricular ejection fraction (LVEF) ≥ 50% in cardiac function examination.
- 11) The serum pregnancy test is negative, and effective contraceptive measures are taken within 6 months from the signing of the informed consent form until the use of the last chemotherapy.
- 12) Thyroid stimulating hormone (TSH), free thyroxine (FT4), or free triiodothyronine (FT3) are all within the normal range of ± 10%.
Key exclusion criteria (10 listed)
- 1) Participating in other clinical studies, or the first study drug administration is less than 4 weeks after the end of the previous clinical study treatment.
- 2) Has suffered from other malignant tumors within the past 5 years. 3) Patients who have received CNS guided treatment and prevention. 4) Patients with a known history of human immunodeficiency virus (HIV) infection and/or acquired immunodeficiency syndrome.
- 5) Patients with active autoimmune diseases or a history of hematological autoimmune diseases with a high risk of recurrence, including but not limited to immune related neuropathy, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain's syndrome, myasthenia gravis, systemic lupus erythematosus, connective tissue disease, scleroderma, inflammatory bowel cancer (including Crohn's disease and ulcerative colitis), autoimmune hepatitis Toxic epidermal necrolysis or Stevens Johnson syndrome.
- 6) Patients with active chronic hepatitis B or active hepatitis C. Patients with positive hepatitis B B surface antigen or hepatitis C virus antibody in screening period must further pass the hepatitis B virus DNA drop test (not more than 1000 iu/ml) and HCV RNA test (not more than the lower limit of the test method), and can be included in the test only after the active hepatitis B or hepatitis C infection requiring treatment is excluded. Hepatitis B virus carriers, hepatitis B patients who are stable after drug treatment and cured hepatitis C patients can be included in the group.
- 7) Suffer from active pulmonary tuberculosis. 8) Currently, there is interstitial lung disease or infectious pneumonia. 9) Active infections that require systematic anti infective treatment, including but not limited to bacterial, fungal, or viral infections.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intrathecal Injection of Thiotepa+Radiation+Systemic Treatment of Primary DiseasesParticipants 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. | Drug | Interventional arm |
Primary outcome
The objective response rate (ORR)
Time frame: 2 years
The proportion of responsive patients according to RANO-LM criteria
9 secondary outcomes
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Time frame: 2 years
The disease control rate(DCR)
Time frame: 2 years
OS
Time frame: 2 years
PFS
Time frame: 2 years
3-month OS
Time frame: 3 months
6-month OS
Time frame: 6 months
9-month OS
Time frame: 9 months
12-month OS
Time frame: 12 months
Mean total score on FACT-G
Time frame: 2 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 May 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Intrathecal Injection of Thiotepa+Radiation+Systemic Treatment of Primary Diseases in people with Solid Tumor Leptomeningeal Metastasis, run by Second Affiliated Hospital, Zhejiang University, School of Medicine at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The objective response rate (ORR) (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 May 2026; AzTrials last refreshed its copy on 31 Oct 2026.