Clinical trial NCT06497543: Intrathecal Pemetrexed for SCLC Patients With Refractory Brain Metastases or Leptomeninges Metastatic
Official title: The Efficacy and Safety of Intrathecal Pemetrexed for SCLC Patients With Refractory Brain Metastases or Leptomeningeal Metastasis: A Phase II Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Small-cell Lung Cancer
Lead sponsor: Hunan Province Tumor Hospital
Sponsor class: OTHER
Collaborators: name: Second People's Hospital of Hunan
First posted: 2024-07-11
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study aimed to evaluate the efficacy and safety of intrathecal pemetrexed for SCLC patients with refractory brain metastases or leptomeningeal metastasis.

Detailed description: This is a prospective interventional clinical study to evaluate the efficacy and safety of intrathecal pemetrexed for SCLC patients with refractory brain metastases or leptomeningeal metastasis. Approximately 80 small cell lung cancer patients with refractory brain and/or leptomeningeal metastasis were enrolled and treated with intrathecal pemetrexed, there were 40 cases in cohort 1 with refractory brain metastasis and 40 cases in cohort 2 with leptomeningeal metastasis.Cerebrospinal fluid samples will be collected before and after pemetrexed resistance to analyze molecular mechanisms. The study is expected to commence recruitment in mainland China in about September 2024. It is expected that the trial will end in April 2026.

Eligibility criteria: Inclusion Criteria:

* 1. Understand the requirements and contents of the clinical trial, and provide a signed and dated informed consent form.
* 2. Age ≥ 18 years.
* 3. Histopathology is confirmed small cell lung cancer .
* 4.Leptomeningeal metastasis (LM) is defined by the presence of typical clinical symptoms, positive cerebrospinal fluid (CSF) cytology, detection of cell-free DNA (cfDNA) in CSF by next-generation sequencing (NGS), or imaging findings consistent with typical meningeal metastases.
* 5.Patients with brain progression after whole-brain radiotherapy.
* 6. Predicted survival ≥ 12 weeks. .
* 7. ECOG 0-2.
* 8. Adequate bone marrow hematopoiesis and organ function.

Exclusion Criteria:

* 1. Previously received intrathecal pemetrexed therapy for locally advanced or metastatic disease.
* 2. Subjects who have received any of the following treatments must be excluded:
* Have received radiation within 14 days prior to the first dose or have not recovered from radiation-related toxicity. Chest and extra-brain palliative radiotherapy, stereotactic radiosurgery, and stereotactic body radiotherapy may be performed 7 days prior to the first dose.
* 3. Presence of spinal cord compression or meningeal metastasis.
* 4. History of other malignant tumors within 2 years.
* 5. Adverse events (except alopecia of any degree) of CTCAE \> grade 1 due to prior treatment (e.g., adjuvant chemotherapy, radiotherapy, etc.) prior to the first dose.
* 6. History of stroke or intracranial hemorrhage within 6 months prior to the first dose.
* 7. The presence of any severe or poorly controlled systemic disease, including poorly controlled hypertension and active bleeding in the judgment of the investigator.
* 8. Subjects with persistent or active infection, including but not limited to hepatitis B (HBV), hepatitis C (HCV), human immunodeficiency virus (HIV) and COVID-19 infection.
* 9. Heart-related diseases or abnormalities
* 10. Past history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis requiring steroid therapy or interstitial lung disease with active clinical symptoms, immune pneumonia caused by immunotherapy.
* 11. Refractory nausea and vomiting, chronic gastrointestinal disease, difficulty swallowing drugs, or inability to adequately absorb sunvozertinib or anlotinib due to previous bowel resection.
* 12. Live vaccine was given 2 weeks before the first medication.
* 13. Women who are breastfeeding or pregnant.
* 14. Hypersensitivity to the test drug and the ingredients.
* 15. Other conditions assessed by the investigator to be unsuitable for participation in the study.

Primary outcomes:
measure: Overall Survival
timeFrame: Time from first subject dose to study completion, or up to last follow up
Secondary outcomes:
measure: Intracranial progression-free survival (I-PFS)
timeFrame: Time from first subject dose to study completion, or up to 36 month
measure: Intracranial Objective Response Rate (I-ORR)
timeFrame: Time from first subject dose to study completion, or up to 36 month
measure: clinical remission rate
timeFrame: Time from first subject dose to study completion, or up to 36 month
measure: Adverse events (AEs)
timeFrame: Time from first subject dose to study completion, or up to 36 month
Other outcomes:
Locations:
city: Changsha
country: China
facility: Yongchang Zhang
state: Hunan
Study officials:
References: