Efficacy and Safety of Intraventricule Pemetrexed Disodium Administered Via Ommaya Reservoir
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age18+
SponsorXiangya Hospital of Central South University
About this trial
This is a open-label, multi-center prospective observation study for the efficacy and safety of intraventricle pemetrexed disodium via ommaya reservoir in the treatment of leptomeningeal metastasis with lung cancer who have failed at least one targeted therapy. In detail: At least the treatment failure was after third-generation EGFR-TKIs in EGFR-mutated lung cancer; or at least the treatment failure was after second-generation ALK-TKIs in ALK-mutated lung cancer; or at least the treatment failure was after one-line of targeted-TKIs in ROS1-mutated non-squamous non-small lung cancer.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
confirmed pathologic diagnosis (histologic type of non-squamous non-small cell lung cancer in the primary lesion or metastatic lesion) with definitely genetic testing results (EGFR/ALK/ROS1);
In accordance with the CSCO Guidelines for the Diagnosis and Management of Central Nervous System Tumors, and the EANO-ESMO diagnostic criteria: a diagnosis of type I meningeal metastatic carcinoma is made when cerebrospinal fluid cytology testing reveals anisocytosis (3 consecutive tests are required if the cerebrospinal fluid cytology testing is initially negative for the patient) (one study showed that the specificity of anisocytosis in diagnosing meningeal metastases in patients with solid tumors was 100%) or meningeal lesions Biopsy confirms the diagnosis. (Type IIA-C meningeal metastases: negative or atypical cerebrospinal fluid cytology, MRI showing linear or/and nodular meningeal enhancement^ with typical clinical symptoms*).
MRI: at least 1.5T; demonstrates sulcal, smear, or linear ventricular enhancement, cranial nerve root enhancement or nodular meningeal enhancement, or cauda equina spinal enhancement; control enhancement T1-weighted sequences and Flair sequences; nodularity is defined as foci of ≥ 5x10mm enhancement; sequences of choice: cranial planar enhancement + T2Flair (enhancement) or and total spinal planar enhancement (when suspicion of spinal involvement); 3D T1 enhancement (involved cranial nerves - optional); cerebrospinal fluid flow imaging (functional or anatomic).
Typical clinical manifestations: headache, nausea, vomiting; epilepsy; mental changes, gait difficulties; cranial nerve damage (diplopia, visual abnormalities, hearing abnormalities, facial nerve palsy, difficulty chewing, difficulty swallowing, choking, etc.); neurogenic signs (cauda equina symptoms, mainly perineal numbness, tingling, defecation and urination disturbances, weakness or incomplete paralysis of both lower limbs); sensorimotor defects of the limbs; cervical back Radicular pain; be careful to differentiate from signs and symptoms of brain parenchymal metastases, extracranial disease, treatment-related adverse effects, and non-tumor comorbidities.
Disqualifiers
HBsAg-positive patients may be enrolled, but patients with higher than normal viral copy number or HBcAb-positive patients should receive effective anti-HBV treatment until 6 months after the end of the trial. HCV RNA carriers may be enrolled, but need to receive effective anti-HCV treatment throughout the trial, and continue to receive effective anti-HCV treatment until 6 months after the end of the trial.
human immunodeficiency virus (HIV) infection.
significant extracranial lesion progression or extensive extracranial lesions causing severe symptoms that cannot be effectively treated.
patients with extreme emaciation or cachexia.
Trial population
non-squamous non-small cell lung cancer with oncogene-driven and failed at least one-line of targeted therepy ( EGFR/ALK/ROS1); At least failure after third-generation EGFR-TKIs in EGFR-mutated lung cancer. At least failure after second-generation ALK-TKIs in ALK-mutated lung cancer. At least failure after one line of targeted-TKIs in ROS1-mutated non-squamous non-small lung cancer.
Trial design
Design model
Cohort
Time perspective
Prospective
Treatments tested in this trial
Pemetrexed injection
DrugGroup 1（20mg）:induction stage is 20 mg per 24 hours for 72 hours, every 2 weeks; consolidation stage is 20mg per 24 hours for 72 hours, every 3 weeks.
Pemetrexed
DrugGroup 2（30mg）:induction stage is 30 mg D1，every week.Consolidation stage is 30 mg D1,every 3 weeks.
Treatment groups
64 Participants
are divided into 2 treatment groupsGroup A: Pemetrexed 20mg2 interventions
Group B: Pemetrexed 30mg2 interventions
Trial outcomes
Primary outcomes
1
Objective response rate，ORR
ORR is the ratio of the patients who achieve the complete remission(CR), obvious remission(OR), or partial remission(PR) to the included patients eligible for efficacy assessment. complete remission(one of the following items): normal RANO；normal Glasgow Coma Scale；KPS≥90. obvious remission(one of the following items): the improvement of at least 70% items on the RNAO examinations; Glasgow Coma Scale≥12 or at lease 3 scores increase compared to baseline; KPS≥70 or at lease 30 scores increase compared to baseline. partial remission(one of the following items)：the improvement of at least 50% items on the RNAO examinations; Glasgow Coma Scale≥9 or at lease 2 scores increase compared to baseline; KPS 50-70 or at lease 20 scores increase compared to baseline.
Time frame
3 monthsSecondary outcomes
1
Disease control rate,DCR
DCR is the ratio of the patients who achieve the CR, OR, PR,or SD to the included patients eligible for efficacy assessment. complete remission(one of the following items): normal RANO；normal Glasgow Coma Scale；KPS≥90. obvious remission(one of the following items): the improvement of at least 70% items on the RNAO examinations; Glasgow Coma Scale≥12 or at lease 3 scores increase compared to baseline; KPS≥70 or at lease 30 scores increase compared to baseline. partial remission(one of the following items)：the improvement of at least 50% items on the RNAO examinations; Glasgow Coma Scale≥9 or at lease 2 scores increase compared to baseline; KPS 50-70 or at lease 20 scores increase compared to baseline. stable disease (one of the following items ):the improved items on the RNAO examinations less than 50%; the change of Glasgow Coma Scale within 1 score compared to baseline; the change of KPS within 10 scores.
Time frame
2 years2
progression-free survival，PFS
time to the progression of disease. Progression of disease(one of the following items): The deterioration of at least 25% items on the RNAO examinations; the drop of Glasgow Coma Scale more than 1 score compared to baseline; the drop of KPS score more than 10 scores.
Time frame
2 years3
overall survival,OS
time to the death or loss of follow-up
Time frame
2 years4
CSF cytology clearance
negative results using glass slide centrifugation accompanied with staining
Time frame
2 yearsSponsors and contacts
Click on the lead sponsor to view all of their trials.
Xiangya Hospital of Central South University
Lead sponsor
First People's Hospital of Chenzhou
Collaborator
Xiangtan Central Hospital
Collaborator
Source ClinicalTrials.gov