Intrathecal Injection Pemetrexed And Bevacizumab in Patients With Leptomeningeal Metastases in NSCLC
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorShanghai Chest Hospital
About this trial
This is a prospective, single-arm, phase Ia clinical study, which was designed to evaluate the efficacy and safety of Pemetrexed Combined With Bevacizumab Intrathecal Injection in Patients With Leptomeningeal Metastases in NSCLC.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age ≥ 18 years;
ECOG PS score 0-3. ECOG PS score 2 or 3 should be due to leptomeningeal metastases.
Patients with pathologically diagnosed non-small cell lung cancer with cerebrospinal fluid and/or MRI diagnosis of leptomeningeal metastasis(LM);
Unsatisfactory efficacy of LM,which defined as disease progression in LM,or LM-related neurological progression, while patients received standard systemic anti-tumor treatment;
Disqualifiers
Positive for human immunodeficiency virus (HIV) ;
History of allergy to pemetrexed or bevacizumab;
History of pemetrexed and/or bevacizumab intrathecal Injection;
Uncontrolled hypertension(systolic pressure≥150mmHg，or diastolic pressure≥100mmHg；History of hypertensive crisis or hypertensive encephalopathy;
Trial design
Design model
Single group
Treatments tested in this trial
Pemetrexed
DrugIntrathecal pemetrexed 50mg,twice per week (d1, d8) for 1 week, then once per 4 weeks
Bevacizumab
DrugIntrathecal bevacizumab, once (d8)for 1 week, then once per 4 weeks.The initial dose of intrathecal bevacizumab is 5 mg, escalated to 10 mg, and then 25 mg, and then 37.5mg, and then 50mg.
Treatment groups
19 Participants
are divided into 2 treatment groupsGroup A: Arm AExperimental treatment 1 intervention
Group B: Arm BExperimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
Incidence of Adverse Events (Safety and Tolerability)
Number of participants with adverse events, treatment emergent adverse events,and serious adverse events assessed by CTCAE v5.0 as a measure of safety and tolerability.
Time frame
From the beginning of the treatment until two months after the treatment.Secondary outcomes
1
Overall Survival (OS)
Kaplan-Meier method used to estimate the distribution of OS from the start of study treatment.
Time frame
Up to 2 yearsOther outcomes
1
Clinical response rate
The evaluation of clinical response rate was assessed by the investigators, which based on improvement of neurologic symptoms/signs and changes in the Karnofsky performance status score . This evaluation consists of five layers, including complete response (CR), obvious response (OR), partial response (PR), stable disease (SD) and progressive disease (PD).Clinical response was defined as the continuous presence of CR, OR or PR within an interval of at least 1 week. SD and PD were defined as ineffective.
Time frame
Up to 2 years2
CSF cytology
Cerebrospinal fluid (CSF) was collected before each cycle of intrathecal treatment, and assessed by the investigators the presence of tumor cells (Positive or Nagetive).
Time frame
From the beginning of the intrathecal treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years3
Radiographic assessment
Radiographic assessment with complete contrast-enhanced neuro-axis MRI or CT, Leptomeningeal metastases response was evaluated using the Response Assessment in Neuro-Oncology (RANO) criteria.
Time frame
From the beginning of the treatment until two months after the treatment.Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Shanghai Chest Hospital
Lead sponsor
Innovent Biologics (Suzhou) Co. Ltd.
Collaborator
Source ClinicalTrials.gov