Combining whole-brain radiotherapy with Thiotepa injection and systemic therapy for treating meningeal metastases in solid tumors

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

This study is testing a new treatment that combines whole-brain radiotherapy with Thiotepa injections to see if it helps people with meningeal metastases from solid tumors feel better.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 58 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University (Academic / other)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Hangzhou, Zhejiang)
• Trial ID: NCT06376292 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the safety and efficacy of a combined treatment approach for patients with meningeal metastases from solid tumors. Participants will receive whole-brain radiotherapy alongside intrathecal injections of Thiotepa, administered twice a week over four weeks. The study will assess the effectiveness of this combination therapy compared to previous treatments and monitor safety through regular evaluations every two cycles. The goal is to determine if this novel approach can improve patient outcomes.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with solid tumors diagnosed with meningeal metastasis and adequate organ function.

Not a fit: Patients with severe organ dysfunction or those who have not met the eligibility criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new effective option for patients suffering from meningeal metastases, potentially improving survival and quality of life.

How similar studies have performed: While this approach is exploratory, previous studies have shown promise in using combined therapies for similar conditions, suggesting potential for success.

Eligibility criteria

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.

  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.

  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.

Where this trial is running

Hangzhou, Zhejiang

• The Second Affiliated Hospital of Zhejiang University — Hangzhou, Zhejiang, China (Recruiting)

Study contacts

• Study coordinator: Ting Zhang, prof.

Conditions Solid Tumor Leptomeningeal Metastasis