Trial Title:
CSF CTC-Capture-Guided EGFR-TKI and Bevacizumab Combination Therapy in EGFR-Mutant Advanced NSCLC
NCT ID:
NCT06557096
Condition:
Non Small Cell Lung Cancer
Circulating Tumor Cell
EGF-R Positive Non-Small Cell Lung Cancer
Conditions: Official terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Neoplastic Cells, Circulating
Bevacizumab
Osimertinib
Study type:
Interventional
Study phase:
Early Phase 1
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Osimertinib 80 MG
Description:
Osimertinib is taken orally at a dose of 80mg daily for a 28-day treatment period,
followed by a sequential treatment of osimertinib 80mg daily taken orally for another 28
days.
Arm group label:
Sequential Treatment cohort
Other name:
Tagrisso
Intervention type:
Drug
Intervention name:
Bevacizumab
Description:
Sequential combination therapy with bevacizumab administered intravenously at a dosage of
7.5mg/kg of body weight on the first day of each cycle, with medication given once every
3 weeks, for a continuous treatment duration of 21 days.
Arm group label:
Sequential Treatment cohort
Other name:
avastin
Summary:
clinical trial The goal of this clinical trial is to learn whether the treatment of
advanced non-small cell lung cancer with EGFR-TKIs, when combined with bevacizumab in the
presence of positive circulating tumor cells in the cerebrospinal fluid, has better
therapeutic efficacy. The main questions it aims to answer are:1.When EGFR-TKIs are
sequentially combined with bevacizumab along with EGFR-TKIs for first-line treatment of
advanced non-small cell lung cancer, how long can the participants survive? 2.What
medical problems do participants have when using EGFR-TKIs sequentially combined with
bevacizumab in conjunction with EGFR-TKIs.
Participants will:
Receive EGFR-TKIs treatment for a duration of 3 months, and upon a positive cerebrospinal
fluid tumor cell status, subsequently receive bevacizumab combined with EGFR-TKIs
treatment until disease progression.
Visit the clinic for check-ups and tests every two weeks, and have follow-up visits every
six weeks after the treatment ends.
Keep a record of their symptoms and disease progression.
Detailed description:
This study is an open-label, single-arm, multicenter, exploratory clinical trial designed
to evaluate and observe the first-line treatment of locally advanced/advanced non-small
cell lung cancer that is positive for EGFR mutations, based on the early warning of a
novel cerebrospinal fluid CTC capture technology. Subjects who meet all inclusion
criteria and none of the exclusion criteria will first receive EGFR-TKIs (osimertinib,
amivantamab, or futibatinib) treatment (as per the instruction manual). After a positive
cerebrospinal fluid tumor cell status, they will then sequentially receive bevacizumab
(7.5mg/kg, intravenous injection, once every 3 weeks) combined with EGFR-TKIs treatment.
Participants Aged 18 years or older (including 18 years old) and up to 75 years of age
(including 75 years old); confirmed non-small cell lung cancer through histology or
cytology; confirmed EGFR sensitive mutation (exon 19 deletion or L858R) prior to
treatment; planned to receive first-line monotherapy with EGFR-TKIs (osimertinib,
amivantamab, or futibatinib).
This study is an open-label, single-arm, multicenter, exploratory clinical trial. The
primary research objective is to evaluate the overall survival time (OS) of patients with
locally advanced/advanced EGFR-mutant non-small cell lung cancer (NSCLC) treated with
EGFR tyrosine kinase inhibitors (EGFR-TKIs) sequentially combined with bevacizumab as a
first-line treatment, based on the early warning of a novel cerebrospinal fluid
circulating tumor cell (CSF CTC) capture technology. The study endpoint is the overall
survival time (OS) of the patients. Referring to the results of our team's prospective
study data and historical literature review study data, it is anticipated that the hazard
ratio (HR) for overall survival (OS) of EGFR-TKIs sequentially combined with bevacizumab
compared to EGFR-TKIs as a first-line treatment for high-risk patients with EGFR-mutant
locally advanced/advanced NSCLC and leptomeningeal metastasis will be 0.78 (median OS
improved from 18 months to 21 months). After the first subject is enrolled, with the
longest observation period being 24 months, α set at two-sided 0.05, and a power of 80%,
calculating with a 25% CSF tumor cell positivity rate and a 10% loss to follow-up rate,
using the NCSS&PASS 15.0 software and the single-sample Logrank test method, after sample
correction, this study plans to enroll approximately 100 subjects.
Based on the investigator-assessed Overall Survival (OS) as the primary efficacy
endpoint, the median survival time will be estimated using the Kaplan-Meier method, and
the median event time along with its two-sided 95% confidence interval will be presented.
Additionally, the hazard ratio and its 95% confidence interval will be estimated as the
main analysis.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- 1.The subjects voluntarily joined this study and signed the informed consent form,
showing good compliance and cooperation with follow-up.
2.Ages between 18 years old (inclusive) and 75 years old (inclusive). 3.ECOG score:
0-2 points. 4.Expected survival of no less than 3 months. 5.According to the RECIST
1.1 criteria, the patient has at least one extracranial target lesion.
6.Diagnosed with non-small cell lung cancer based on histology or cytology. 7.No
leptomeningeal metastasis (EANO criteria). 8.The tumor tissue samples or blood
samples are confirmed to have EGFR-sensitive mutations (including exon 19 deletions
or L858R).
9.Have not received systemic anti-tumor treatment, and are planned to receive
first-line monotherapy with osimertinib, aumolertinib, or furmonertinib.
10.The main organ functions are normal, that is, they meet the following criteria:
1. The standard for routine blood test should meet: HB≥90 g/L; ANC≥1.5×10^9/L;
PLT≥80×10^9/L.
2. The biochemical examination should meet the following standards: TBIL<1.5×ULN;
ALT and AST<2.5×ULN; serum Cr≤1.25×ULN or endogenous creatinine clearance > 45
ml/min (Cockcroft-Gault formula). 11.Women of childbearing age must have taken
reliable contraceptive measures and have undergone a pregnancy test (serum or
urine) within 7 days before enrollment, with a negative result, and must be
willing to use appropriate methods of contraception during the trial period and
for 8 weeks after the last administration of the trial medication. For men,
they must agree to use appropriate methods of contraception during the trial
period and for 8 weeks after the last administration of the trial medication or
have undergone surgical sterilization.
Exclusion Criteria:
1. Subjects have received any of the following treatments:
1. Previously used any EGFR tyrosine kinase inhibitors;
2. Previously received any chemotherapy for lung cancer;
3. Previously received any radiotherapy for lung cancer (except for palliative
radiotherapy for bone metastases);
4. Within 4 weeks before the first administration of the study medication, the
subject had undergone major surgery;
5. Within 7 days before the first administration of the study medication, used
strong inhibitors or inducers of CYP3A4.
2. Subjects with concurrent other malignant tumors, except for basal cell carcinoma of
the skin and in situ cancer.
3. Subjects have uncontrollable malignant pleural effusion and pericardial effusion.
4. Subjects who are allergic to contrast agents used in CT and MRI or who cannot
tolerate MRI examinations.
5. As judged by the investigator, there are any serious or poorly controlled systemic
diseases, such as poorly controlled hypertension, active bleeding diathesis, or
active infection.
6. Clinically severe gastrointestinal dysfunction that may affect the intake,
transport, or absorption of medication, such as the inability to take oral
medication, uncontrollable nausea or vomiting, a history of extensive
gastrointestinal resection, untreated recurrent diarrhea, atrophic gastritis,
gastric diseases requiring long-term use of proton pump inhibitors that have not
been cured, Crohn's disease, ulcerative colitis, etc.
7. Hepatic encephalopathy, hepatorenal syndrome, or liver cirrhosis.
8. Meet any of the following cardiac examination results:
1. The average value of the corrected QT interval (QTcF) derived from three
electrocardiograms (ECG) at rest using the Fridericia formula is > 470 msec;
2. Resting ECG indicates conduction or ECG morphological abnormalities (such as
complete left bundle branch block, third-degree atrioventricular block,
second-degree atrioventricular block, and PR interval > 250 msec, etc.);
3. There are any factors that increase the risk of QTc prolongation or arrhythmic
events, such as heart failure, hypokalemia, congenital long QT syndrome, family
history of long QT syndrome, or any concomitant medication of unexplained
sudden death in direct relatives under 40 years old or prolonged QT interval;
4. The left ventricular ejection fraction (LVEF) is < 50%.
9. Insufficient bone marrow reserve or organ function, meeting any of the following
laboratory limits:
1. Absolute neutrophil count <1.5×10^9/L;
2. Platelet count <100×10^9/L;
3. Hemoglobin <90 g/L (<9 g/dL);
4. If there is no clear liver metastasis, alanine aminotransferase (ALT) > 3 times
the upper limit of normal (ULN); if there is liver metastasis, ALT > 5×ULN;
5. If there is no clear liver metastasis, aspartate aminotransferase (AST) >
3×ULN; if there is liver metastasis, AST > 5×ULN;
6. If there is no clear liver metastasis, total bilirubin > 1.5×ULN; or with
Gilbert's syndrome (unconjugated hyperbilirubinemia) or liver metastasis, total
bilirubin > 3×ULN;
7. Creatinine > 1.5×ULN and creatinine clearance <50 mL/min (calculated by the
Cockcroft-Gault formula); creatinine clearance is only required to be confirmed
if creatinine > 1.5×ULN;
8. Serum albumin (ALB) <28 g/L.
10. Active fungal, bacterial, and/or viral infections requiring systemic treatment.
11. Female subjects who are pregnant, breastfeeding, or planning to become pregnant
during the study period.
12. History of interstitial lung disease, drug-induced interstitial lung disease,
history of radiation pneumonitis requiring steroid treatment, or any evidence of
clinically active interstitial lung disease.
13. Subjects judged by the investigator to be likely non-compliant with the study
procedures and requirements, such as those with a clear history of neurological or
psychiatric disorders, or currently suffering from psychiatric disorders.
14. Subjects judged by the investigator to have any conditions that may endanger the
subject's safety or interfere with the study assessment.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Start date:
August 20, 2024
Completion date:
July 31, 2028
Lead sponsor:
Agency:
Second Affiliated Hospital of Nanchang University
Agency class:
Other
Source:
Second Affiliated Hospital of Nanchang University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06557096
