Intrathecal Pemetrexed for Leptomeningeal Metastasis in EGFR-Mutant NSCLC
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age20+
SponsorTaipei Veterans General Hospital, Taiwan
About this trial
Leptomeningeal metastasis (LM) is a complication of advanced non-small cell lung cancer (NSCLC). The incidence of LM in NSCLC patients is around 3-5 %, reaching 9.4 % of those with an epidermal growth factor receptor (EGFR) mutation. Generally, the efficacy of systemic treatment for LM is limited due to the blood-brain barrier. Osimertinib has a high central nervous system penetration rate, making it the preferred first-line treatment for EGFR-mutant NSCLC. Previous studies indicated that osimertinib had shown promising efficacy in pretreated patients harboring EGFR mutations and LM. However, intracranial disease progression eventually develops, and the prognosis of patients with LM progression after osimertinib is poor. Recently, intrathecal chemotherapy with pemetrexed (IP) was reported to be an alternative treatment in patients with NSCLC and LM. The results from a phase I/II trial examining the efficacy and safety of IP in patients with EGFR-mutant NSCLC after the failure of previous TKI, and 83% of study enrollees received osimertinib before IP. The clinical response rate was 84.6%, and the median overall survival was 9.0 months. Despite initial promising efficacy, further trials are needed to verify these results. Therefore, the investigators plan to conduct a prospective study to examine the safety and effectiveness of IP combined with EGFR-TKI for patients with EGFR mutant NSCLC after osimertinib failure.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
At least 20 years of age.
Patients with metastatic non-squamous NSCLC harboring known EGFR activating mutation and with a diagnosis of probable or confirmed LM by the European Association of Neuro-Oncology-European Society for Medical Oncology (EANO-ESMO) guideline. [5] EGFR activating mutations include exon19 deletion, T790M, L858R, G719X, L861Q, or S768I.
Intracranial disease progression after osimertinib use, proved by contrast-enhanced MRI
Stable extra-cranial disease status, judged by investigators.
Disqualifiers
Uncontrolled extra-CNS disease which needs other systemic treatment than EGFR-TKI.
Uncontrolled tumor-related pain
Uncontrolled or symptomatic hypercalcemia (> 1.5 mmol/L ionized calcium or Ca > 12 mg/dL or corrected serum calcium > ULN). Patients who are receiving denosumab prior to study enrollment must be willing and eligible to receive a bisphosphonate instead while in the study.
Malignancies other than NSCLC within 5 years prior to study enrollment, with the exception of those with a negligible risk of metastasis or death (e.g., expected 5-year OS > 90%) treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous-cell skin cancer, localized prostate cancer treated surgically with curative intent, ductal carcinoma in situ treated surgically with curative intent)
Trial design
Design model
Single group
Treatments tested in this trial
Pemetrexed
DrugIntrathecal Pemetrexed
Treatment groups
23 Participants
are divided into 1 treatment groupGroup A: Experimental armExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Disease control rate (DCR)
The response to treatment was determined by combining neurological examination, CSF cytology, and radiographic evaluation by RANO-LM proposal.
Time frame
Every 6 weeks till disease progression, an average of 6 monthsSecondary outcomes
1
Progression-free Survival, LM (PFS-LM)
PFS is measured from the date of study enrollment to documented progression of LM according to RANO LM working group or death from any cause.
Time frame
Every 6 weeks till disease progression, an average of 6 months2
Progression-free Survival (PFS)
PFS is measured from the date of study enrollment to radiographically documented progression according to RECIST 1.1 or death from any cause (whichever occurs first). Participants alive and without disease progression or lost to follow-up will be censored at the date of their last radiographic assessment.
Time frame
Every 3 months till disease progression, an average of 6 months3
Overall survival (OS)
OS is measured from date of study enrollment to the date of death from any cause
Time frame
Every 3 months through study completion , an average of 12 monthsSponsors and contacts
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Source ClinicalTrials.gov