Clinical trial NCT06440954: Efficacy and Resistance Mechanisms of IP in NSCLC With Leptomeningeal Metastases
Official title: To Investigate the Efficacy and Resistance Mechanisms of Intrathecal Pemetrexed in Advanced Non-small Cell Lung Cancer (NSCLC) Patients Harboring Oncogenic Mutations With Leptomeningeal Metastases
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Non-Small Cell Lung Cancer
Lead sponsor: Hunan Province Tumor Hospital
Sponsor class: OTHER
Collaborators: name: Hunan Cancer Hospital
First posted: 2024-06-04
Enrollment: 220
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a prospective interventional study clinical study to investigate the efficacy and resistance mechanisms of intrathecal pemetrexed in patients with driver gene mutations advanced NSCLC with leptomeningeal metastases.

Detailed description: This is a prospective interventional clinical study aimed at investigating the efficacy and resistance mechanisms of intrathecal pemetrexed in advanced NSCLC patients with EGFR, ALK, and ROS1 mutations presenting leptomeningeal metastases. Approximately 30 advanced NSCLC patients with EGFR, ALK, and ROS1 mutations, who have developed leptomeningeal metastases following TKI resistance, will receive intrathecal pemetrexed. Cerebrospinal fluid samples will be collected before and after pemetrexed resistance to analyze molecular mechanisms and differences. Second-generation gene detection will be performed to identify potential resistance mechanisms to pemetrexed. The study is expected to commence recruitment in mainland China around April 2024, with an anticipated completion date in April 2025.

Eligibility criteria: Inclusion Criteria:

1. Age ≥ 18 years.
2. Histopathology or cytology confirmed metastatic non-small cell lung cancer with leptomeningeal metastasis after TKI resistant.
3. EGFR mutant, ALK fusion, ROS1 fusion, and other oncogenic alterations including RET fusion, BRAF mutation, NTRK fusion, KRAS mutation was confirmed by an accredited local laboratory.
4. Adequate bone marrow hematopoiesis and organ function
5. Agree to receive intrathecal pemetrexed
6. ECOG 0 - 2.
7. Predicted survival ≥ 12 weeks.

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: Intracranial progression-free survival (I-PFS)
timeFrame: Time from first subject dose to study completion, or up to 36 month
Secondary outcomes:
measure: System progression-free survival (s-PFS)
timeFrame: Time from first subject dose to study completion, or up to 36 month
Other outcomes:
measure: Overall Survival Time
timeFrame: Time from first subject dose to study completion, or up to 36 month
Locations:
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
Study officials:
affiliation: Hunan Cancer Hospital
name: Yongchang Zhang
role: PRINCIPAL_INVESTIGATOR
References: