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

NCT06557096 | Not Yet Recruiting Early Phase 1

• 1 other identifier: IIT-2024-7604A
• Study Type: interventional
• Target: 100
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Non Small Cell Lung Cancer; Circulating Tumor Cell; EGF-R Positive Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (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.

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

Secondary Outcomes (3)

• Objective response rate (ORR)

  Within 8 weeks after completion of treatment

• Progression free survival (PFS)

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

• Duration of Response (DOR)

  Up to 2 years after completion of treatment

Study Arms (1)

Sequential Treatment cohort

EXPERIMENTAL

Participants 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.

Drug: Osimertinib 80 MG; Drug: Bevacizumab

Interventions

Osimertinib 80 MG DRUG

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.

Also known as: Tagrisso

Sequential Treatment cohort

Bevacizumab DRUG

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.

Also known as: avastin

Sequential Treatment cohort

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The subjects voluntarily joined this study and signed the informed consent form, showing good compliance and cooperation with follow-up.
• 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.
• 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).
• Have not received systemic anti-tumor treatment, and are planned to receive first-line monotherapy with osimertinib, aumolertinib, or furmonertinib.
• 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.

You may not qualify if:

• 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.
• 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.);

Sponsors & Collaborators

• Second Affiliated Hospital of Nanchang University: lead

Related Publications (5)

• 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.

  PMID: 15886314 BACKGROUND

• 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.

  PMID: 20087963 BACKGROUND

• 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.

  PMID: 24002608 BACKGROUND

• 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.

  PMID: 20573926 BACKGROUND

• 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.

  PMID: 19470276 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Neoplastic Cells, Circulating

Interventions

osimertinib; Bevacizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neoplasm Metastasis; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Lin Chuyang, Director

  Nanchang University

  STUDY DIRECTOR

Central Study Contacts

Huang Long, MD

CONTACT

+86 13699549060; huanglongdoctor@163.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 13, 2024
• First Posted: August 16, 2024
• Study Start: August 20, 2024
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): July 31, 2028
• Last Updated: August 16, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share