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Non Small Cell Lung CancerEarly Phase 1NCT06557096

CSF CTC-Capture-Guided EGFR-TKI and Bevacizumab Combination Therapy in EGFR-Mutant Advanced NSCLC

A Early Phase 1 study testing Osimertinib 80 MG and Bevacizumab in people with Non Small Cell Lung Cancer and Circulating Tumor Cell, run by Second Affiliated Hospital of Nanchang University.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 75 years
What is being tested?
Osimertinib 80 MG and Bevacizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
100 participants
Where
No sites listed yet
Study dates
20 Aug 2024to 31 Jul 2028
Phase
Early Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
  • The standard for routine blood test should meet: HB≥90 g/L; ANC≥1.5×10^9/L; PLT≥80×10^9/L.
  • 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.

Who cannot join

  • Subjects have received any of the following treatments:
  • Previously used any EGFR tyrosine kinase inhibitors;
  • Previously received any chemotherapy for lung cancer;
  • Previously received any radiotherapy for lung cancer (except for palliative radiotherapy for bone metastases);
  • Within 4 weeks before the first administration of the study medication, the subject had undergone major surgery;
  • Within 7 days before the first administration of the study medication, used strong inhibitors or inducers of CYP3A4.
Show all 31Show fewer
  • Subjects with concurrent other malignant tumors, except for basal cell carcinoma of the skin and in situ cancer.
  • Subjects have uncontrollable malignant pleural effusion and pericardial effusion.
  • Subjects who are allergic to contrast agents used in CT and MRI or who cannot tolerate MRI examinations.
  • 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.
  • 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.
  • Hepatic encephalopathy, hepatorenal syndrome, or liver cirrhosis.
  • Meet any of the following cardiac examination results:
  • The average value of the corrected QT interval (QTcF) derived from three electrocardiograms (ECG) at rest using the Fridericia formula is > 470 msec;
  • 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.);
  • 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;
  • The left ventricular ejection fraction (LVEF) is < 50%.
  • Insufficient bone marrow reserve or organ function, meeting any of the following laboratory limits:
  • Absolute neutrophil count <1.5×10^9/L;
  • Platelet count <100×10^9/L;
  • Hemoglobin <90 g/L (<9 g/dL);
  • 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;
  • If there is no clear liver metastasis, aspartate aminotransferase (AST) > 3×ULN; if there is liver metastasis, AST > 5×ULN;
  • 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;
  • 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;
  • Serum albumin (ALB) <28 g/L.
  • Active fungal, bacterial, and/or viral infections requiring systemic treatment.
  • Female subjects who are pregnant, breastfeeding, or planning to become pregnant during the study period.
  • 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.
  • 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.
  • Subjects judged by the investigator to have any conditions that may endanger the subject's safety or interfere with the study assessment.

Trial locations and contacts

No sites are listed yet. Contact the study team or a site near you to ask about taking part.

Huang Long, MD contact

+86 13699549060

huanglongdoctor@163.com

About this study

Official title: Open-label, Single-Arm, Multicenter Clinical Study of EGFR-TKIs Sequentially Combined With Bevacizumab for the Treatment of EGFR-Mutant Advanced Non-Small Cell Lung Cancer, Based on Early Warning by CSF CTC Capture Technology

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:

Read more

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.

Read the 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.

Being tested
Osimertinib 80 MG, Bevacizumab
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Neoplastic Cells, Circulating

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Osimertinib 80 MGDrug

    Also called Tagrisso

    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.

  • BevacizumabDrug

    Also called avastin

    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.

Study groups in NCT06557096
Study groupRoleWhat they receive
Sequential Treatment cohortExperimentalParticipants receive osimertinib orally at a dose of 80mg daily for a 28-day treatment period. After the start of treatment, cerebrospinal fluid is collected every 12 weeks for circulating tumor cell (CTC) examination and routine cytopathological assessment. If the routine cytopathological test is positive, participants are sequentially treated with continued osimertinib at 80mg daily, in combination 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. A continuous treatment of 21 days constitutes one treatment cycle. After the initiation of treatment, cerebrospinal fluid is collected every 6 weeks for CTC testing and routine cytopathological examination.
Receives: Drug: Osimertinib 80 MG; Drug: Bevacizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Survival（OS）

    From the time of a patient's diagnosis or the commencement of treatment, to the time of the patient's death.Will be estimated using Kaplan-Meier product-limit method. The median OS times with two-sided 95% CIs will be estimated.

    Measured: From the start of therapy until death due to any cause, assessed up to 2 years after completion of treatment

Secondary outcomes (3)

  1. Objective response rate (ORR)

    Defined as the percentage of participants having an objective response (complete response [CR] or partial response [PR]), according to Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. The ORR of the drug will be assessed according to Simon's two stage design. The estimated ORR will be compared to the response rate specified in the null hypothesis (6%) using one-sided exact binomial test at type I error 5%. 95% confidence interval (C.I.) will be also reported.

    Measured: Within 8 weeks after completion of treatment

  2. Progression free survival (PFS)

    Will be determined by the immune complete response (iCR). Will be estimated using Kaplan-Meier product-limit method. The median PFS times with two-sided 95% CIs will be estimated.

    Measured: From the start of therapy until disease progression, or death due to any cause, assessed up to 2 years after completion of treatment

  3. Duration of Response (DOR)

    Defined as the time from an initial objective response (CR or PR) according to RECIST v 1.1 until disease progression, or death due to any cause, as determined by iCR.

    Measured: Up to 2 years after completion of treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Aug 2024
  2. Study start20 Aug 2024 (estimated)
  3. Primary completion1 Jun 2027 (estimated)
  4. Study completion31 Jul 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Early Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
100 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06557096
Sponsor's protocol ID
IIT-2024-7604A
Status last verified
Jul 2024
First submitted
13 Aug 2024
Last updated
16 Aug 2024
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Pisters KM, Le Chevalier T. Adjuvant chemotherapy in completely resected non-small-cell lung cancer. J Clin Oncol. 2005 May 10;23(14):3270-8. doi: 10.1200/JCO.2005.11.478.

    PubMed 15886314

  • Bonomi PD. Implications of key trials in advanced nonsmall cell lung cancer. Cancer. 2010 Mar 1;116(5):1155-64. doi: 10.1002/cncr.24815.

    PubMed 20087963

  • Gahr S, Stoehr R, Geissinger E, Ficker JH, Brueckl WM, Gschwendtner A, Gattenloehner S, Fuchs FS, Schulz C, Rieker RJ, Hartmann A, Ruemmele P, Dietmaier W. EGFR mutational status in a large series of Caucasian European NSCLC patients: data from daily practice. Br J Cancer. 2013 Oct 1;109(7):1821-8. doi: 10.1038/bjc.2013.511. Epub 2013 Sep 3.

    PubMed 24002608

  • Maemondo M, Inoue A, Kobayashi K, Sugawara S, Oizumi S, Isobe H, Gemma A, Harada M, Yoshizawa H, Kinoshita I, Fujita Y, Okinaga S, Hirano H, Yoshimori K, Harada T, Ogura T, Ando M, Miyazawa H, Tanaka T, Saijo Y, Hagiwara K, Morita S, Nukiwa T; North-East Japan Study Group. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med. 2010 Jun 24;362(25):2380-8. doi: 10.1056/NEJMoa0909530.

    PubMed 20573926

  • Burtness B, Anadkat M, Basti S, Hughes M, Lacouture ME, McClure JS, Myskowski PL, Paul J, Perlis CS, Saltz L, Spencer S. NCCN Task Force Report: Management of dermatologic and other toxicities associated with EGFR inhibition in patients with cancer. J Natl Compr Canc Netw. 2009 May;7 Suppl 1:S5-21; quiz S22-4. doi: 10.6004/jnccn.2009.0074.

    PubMed 19470276

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Osimertinib 80 MG and Bevacizumab in people with Non Small Cell Lung Cancer and Circulating Tumor Cell, run by Second Affiliated Hospital of Nanchang University.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 16 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Huang Long, MD (+86 13699549060, huanglongdoctor@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Survival（OS） (time frame: From the start of therapy until death due to any cause, assessed up to 2 years after completion of treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06557096, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Aug 2024; AzTrials last refreshed its copy on 6 Nov 2026.

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