Double Dose of Third-generation EGFR-TKI Plus Intrathecal Pemetrexed Versus Double Dose of Third-generation EGFR-TKI in Patients With LM Progression Following the Treatment of Routine Dose of Third-generation EGFR-TKI

June 3, 2024 updated by: Fujian Cancer Hospital

Double Dose of Third-generation EGFR-TKI Plus Intrathecal Pemetrexed Versus Double Dose of Third-generation EGFR-TKI in NSCLC Patients With Leptomeningeal Progression Following the Treatment of Routine Dose of Third-generation EGFR-TKI: a Phase II Randomized, Multicenter Study

We aim to compare the efficacy and safety of double Dose of Third-generation EGFR-TKI Plus Intrathecal Pemetrexed Versus double Dose of Third-generation EGFR-TKI in patients with leptomeningeal progression following the treatment of routine dose of EGFR-TKI,

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

112

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age 18 years at the time of signing informed consent, both sexes;
  • advanced or metastatic NSCLC, TNM stage IV according to the eighth edition of IASLC 2015;
  • with EGFR sensitive mutation (exon 19 deletion or L858R mutation), LM progression after conventional doses of three generation EGFR targeted agents (after 1 + 3,2 + 3 or direct 3-generation targeted therapy). There is no limit on the number of chemotherapy lines. The enrolled patients required brain parenchyma and extracranial lesion stable
  • ECOG PS score: 0-3

  • Normal main organ function, That is, the following criteria are met:

    1. routine blood examination (no blood transfusion within 14 days, no hematopoietic stimulating factor drugs are corrected state): hemoglobin (Hb) 90g / L; Absolute neutrophil count (ANC) 1.5109 / L; Platelet (PLT) 100109 / L; White blood cell count (WBC) 3.0109 / L;
    2. Biochemical examination: alanine transaminotransferase (ALT) and alanine transaminotransferase (AST) 2.5 upper limit of normal (ULN); Serum total bilirubin (TBIL) 1.5 ULN; Serum creatinine (Cr) of 1.5 ULN or creatinine clearance of 50 ml/min; If any liver metastasis, Then, the total bilirubin 3 ULN, ALT and AST 5 ULN; C) Coagulation function: activated partial thromboplastin time (APTT), international normalized ratio (INR), prothrombin time 12 (PT) 1.5 ULN;

    d) Doppler ultrasound assessment: left ventricular ejection fraction (LVEF) 50%;

  • If previously treated with chemotherapy, A washout period of at least 21 days between the last chemotherapy dose and enrollment (if the patient does not receive radiotherapy) is required; Patients who treated brain parenchymal metastases with local radiotherapy or surgery before enrollment, Must be completed and fully recovered from the acute toxicity of radiotherapy / surgery. A minimum 14-day washout period is required between the end of radiotherapy and enrollment. A minimum 30-day washout period is required between the end of surgery and enrollment.
  • Expected survival of not less than 3 months
  • patients can swallow oral medication (if not oral, can be ground by gastric tube)
  • Women of childbearing age must have negative pregnancy test (serum or urine) within 14 days before observation period and 3 months after the last administration; for men, they should undergo surgical sterilization or agree to use appropriate contraception during the observation period and 3 months after the last administration of study drug
  • patients voluntarily participate and sign an informed consent (or legal agent), expected to have good compliance and able to cooperate with the study according to the protocol requirements.

Exclusion Criteria:

  • Major surgery within 4 weeks before starting study treatment or scheduled for surgery during the study program;
  • Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS)
  • patient with active bacterial infection, fungal infection (intravenous antibiotics required at initiation of study treatment);
  • past history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonia requiring steroid therapy, Or any signs of clinically active interstitial lung disease;
  • arterial / venous thrombosis events within 6 months prior to enrollment, Such as cerebrovascular accident (including temporary ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism;
  • congestive heart failure (NYHA grade> 2); unstable angina pectoris; a myocardial infarction within 3 months prior to signing an ICF; any 12 supraventricular or ventricular arrhythmia requiring treatment or intervention; Mean QTcF> 470ms from 3 ECG recordings
  • other systemic malignancies in the last 5 years, (Except for cured skin basal cell carcinoma and cervical situ carcinoma and ovarian carcinoma);
  • Use drugs or supplements known to be the main cause of CYP3A4.
  • Persons known to be allergic to any test drug or its excipients;
  • pregnant, lactating, reproductive patients unwilling to use effective contraception; ●a clear prior history of neurological or psychiatric disorders, including epilepsy and dementia;
  • other conditions considered inappropriate by the investigator.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Double Dose of Third-generation EGFR-TKI Plus Intrathecal Pemetrexed
Drug: Double Dose of Third-generation EGFR-TKI
Double Dose of Third-generation EGFR-TKI
Drug: Intrathecal Pemetrexed
Intrathecal Pemetrexed
Active Comparator: Double Dose of Third-generation EGFR-TKI
Drug: Double Dose of Third-generation EGFR-TKI
Double Dose of Third-generation EGFR-TKI

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Overall Survival
Time Frame: From date of randomization until the date of death from any cause assessed up to 12 months after the last patient enrollment
From date of randomization until the date of death from any cause assessed up to 12 months after the last patient enrollment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Quality of life by using QLC 30 questionnaire
Time Frame: every 4 weeks, from date of randomization until the date of first documented progression or date of death from any cause, whichever came first assessed up to 12 months after the last patient enrollment
By using QLC 30 questionnaire to investigate the impact of treatment on patients' QoL specifically the physical and neurological function in patients
every 4 weeks, from date of randomization until the date of first documented progression or date of death from any cause, whichever came first assessed up to 12 months after the last patient enrollment
LM-PFS
Time Frame: From date of randomization until the date of first documented LM progression or date of death from any cause, whichever came first assessed up to 12 months after the last patient enrollment
From date of randomization until the date of first documented LM progression or date of death from any cause, whichever came first assessed up to 12 months after the last patient enrollment
LM-ORR
Time Frame: From date of randomization until the date of first documented LM progression assessed up to 12 months after the last patient enrollment
From date of randomization until the date of first documented LM progression assessed up to 12 months after the last patient enrollment
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time Frame: From date of randomization until the date of first documented LM progression or date of death from any cause, whichever came first assessed up to 12 months after the last patient enrollment
Safety and tolerability
From date of randomization until the date of first documented LM progression or date of death from any cause, whichever came first assessed up to 12 months after the last patient enrollment
exLM-PFS
Time Frame: From date of randomization until the date of first documented non-LM progression or date of death from any cause, whichever came first assessed up to 12 months after the last patient enrollment
From date of randomization until the date of first documented non-LM progression or date of death from any cause, whichever came first assessed up to 12 months after the last patient enrollment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fujian Cancer Hospital

Investigators

  • Principal Investigator: Gen Lin, Fujian Provincial Cancer Hospital, Fuzhou, Fujian, China

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

October 1, 2024

Primary Completion (Estimated)

April 1, 2028

Study Completion (Estimated)

October 1, 2028

Study Registration Dates

First Submitted

May 3, 2024

First Submitted That Met QC Criteria

June 3, 2024

First Posted (Actual)

June 4, 2024

Study Record Updates

Last Update Posted (Actual)

June 4, 2024

Last Update Submitted That Met QC Criteria

June 3, 2024

Last Verified

June 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SQS2024-175

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Leptomeningeal Metastasis

Clinical Trials on Double Dose of Third-generation EGFR-TKI

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Angola

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe