A Prospective Study of Whole-Brain RT Combined With Thiotepa Sheath Injection Combined With Systemic Therapy for the Primary Disease in the Treatment of Meningeal Metastases in Solid Tumors

Phase 2

Recruiting

• Conditions: Solid Tumor Leptomeningeal Metastasis
• Interventions: Drug: Intrathecal Injection of Thiotepa+Radiation+Systemic Treatment of Primary Diseases

• Registration Number: NCT06376292
• Lead Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University

Brief 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 sheath injection combined With Systemic Therapy for the Primary Disease in the Treatment of Meningeal Metastases in Solid Tumors

How works well was the combined therapy？ How safe was combined therapy？ Participants will receive whole brain radiotherapy combined with intrathecal injection of Thiotepa twice a week for a total of 4 weeks. Evaluate the efficacy and safety every 2 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 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) twice a week for a total of 4 weeks. Thiotepa was injected 10mg each time, mixed with cerebrospinal fluid, and then injected slowly for 5-10 minutes. Evaluate the efficacy and safety every 2 cycles.

Study Timeline

• Status Verified: 2024-02
• Study Start: 2024-02-01
• Study First Submitted: 2024-02-27
• Study First Submitted QC: 2024-04-16
• Last Update Submitted: 2024-04-16
• Study First Posted: 2024-04-19
• Last Update Posted: 2024-04-19
• Primary Completion: 2026-02-01
• Study Completion: 2026-02-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

• 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):

  1. 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).

  2. 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).

  3. Renal function: Serum creatinine ≤ 1.5 times the upper limit of normal value.

  4. 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).

     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.

Exclusion Criteria

• 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. Individuals with a history of mental illness; Individuals with no or limited capacity for behavior.

  9. 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.

  10. Other researchers believe that patients who are not suitable to participate in this study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Interventional arm	Intrathecal Injection of Thiotepa+Radiation+Systemic Treatment of Primary Diseases	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.

Primary Outcome Measures

Name	Time	Method
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]	2 years	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.

Secondary Outcome Measures

Name	Time	Method
OS	2 years	overall survival
3-month PFS	3 months	3-month progression free survival
6-month PFS	6 months	6-month progression free survival
1-year PFS	1 years	1-year progression free survival

Trial Locations

Locations (1)

The Second Affiliated Hospital of Zhejiang University; 🇨🇳 Hangzhou, Zhejiang, China