Efficacy and Resistance Mechanisms of IP in NSCLC With Leptomeningeal Metastases

NCT ID: NCT06440954

Last Updated: 2024-06-04

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 220 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-05-01
• Study Completion Date: 2027-04-30

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.

Conditions

Non-Small Cell Lung Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Intrathecal pemetrexed

Intrathecal pemetrexed

Group Type: EXPERIMENTAL

Intrathecal pemetrexed

Intervention Type: DRUG

Intrathecal pemetrexed(50mg) twice a week for 1 week (day 1 and day 5) as induction treatment, then once monthly until progressive disease.

Interventions

Intrathecal pemetrexed

Intrathecal pemetrexed(50mg) twice a week for 1 week (day 1 and day 5) as induction treatment, then once monthly until progressive disease.

Intervention Type: DRUG

Other Intervention Names

pemetrexed

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hunan Cancer Hospital

OTHER

Sponsor Role: collaborator

Hunan Province Tumor Hospital

OTHER

Sponsor Role: lead

Responsible Party

Yongchang Zhang

professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Yongchang Zhang

Role: PRINCIPAL_INVESTIGATOR

Hunan Cancer Hospital

Locations

Hunan Cancer Hospital

Changsha, Hunan, China

Site Status: RECRUITING

Countries

China

Central Contacts

Zhang Yongchang, professor

Role: CONTACT

zhanglei1152@126.com

13873123436

Liang Zeng

Role: CONTACT

530490930@qq.com

15974139200

Facility Contacts

Yongchang Zhang, MD

Role: primary

zhangyongchang@csu.edu.cn

+86 731 89762323

Role: backup

zhangyongchang@csu.edu.cn

Other Identifiers

20240442

Identifier Type: -

Identifier Source: org_study_id