Investigating intrathecal pemetrexed for advanced lung cancer with brain metastases

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

This study is testing whether a special treatment called intrathecal pemetrexed can help people with advanced lung cancer that has spread to the brain and who haven't responded to other therapies.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 220 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Hunan Province Tumor Hospital (Academic / other)
• Drugs / interventions: sunvozertinib, anlotinib, chemotherapy, immunotherapy, radiation
• Locations: 1 site (Changsha, Hunan)
• Trial ID: NCT06440954 on ClinicalTrials.gov

What this trial studies

This prospective interventional study aims to evaluate the efficacy and resistance mechanisms of intrathecal pemetrexed in patients with advanced non-small cell lung cancer (NSCLC) who have leptomeningeal metastases and specific driver gene mutations. Approximately 30 patients will be enrolled, all of whom have experienced resistance to prior targeted therapies. The study will involve collecting cerebrospinal fluid samples before and after treatment to analyze molecular changes and identify potential resistance mechanisms. Recruitment is expected to begin in mainland China in April 2024, with completion anticipated by April 2025.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with confirmed metastatic NSCLC and specific genetic mutations who have developed leptomeningeal metastases after resistance to targeted therapies.

Not a fit: Patients who have previously received intrathecal pemetrexed therapy or those with recent radiation treatment may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new treatment option for patients with advanced NSCLC and leptomeningeal metastases, potentially improving their outcomes.

How similar studies have performed: While the approach of using intrathecal pemetrexed is novel for this specific patient population, similar studies have explored targeted therapies in advanced NSCLC, indicating potential for success.

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.

Where this trial is running

Changsha, Hunan

• Hunan Cancer Hospital — Changsha, Hunan, China (Recruiting)

Study contacts

• Principal investigator: Yongchang Zhang — Hunan Cancer Hospital
• Study coordinator: Zhang Yongchang, professor

Conditions Non-Small Cell Lung Cancer