AzTrials
AzTrials

NSCLCATTRACTNCT04944069

Almonertinib With Bevacizumab for EGFR-Mutant NSCLC Patients With Leptomeningeal Metastasis

A study testing Almonertinib and Bevacizumab in people with NSCLC and Leptomeningeal Metastasis, run by Second Affiliated Hospital of Nanchang University at 1 site in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
Search all trials

Trial summary

A prospective, open-label, multi-center, single-arm study of Almonertinib combined With Bevacizumab for EGFR-mutant NSCLC patients with leptomeningeal metastasis. Read more about this study

Who is it for?
Ages 18 to 75 years
What is being tested?
Almonertinib and Bevacizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
69 participants
Where
1 siteChina
Study dates
Jul 2021to Mar 2025
Phase
Interventional
Are there results?
None posted in the registry

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

  • Male or female, age in 18-75 years.
  • The Eastern Cooperative Oncology Group (ECOG) physical status score is 0-2 and has not deteriorated in the previous 2 weeks, with a minimum expected survival of 12 weeks.
  • Histologically confirmed patients with NSCLC leptomeningeal metastasis by positive cerebrospinal fluid cytological examination.
  • Tumor tissue samples or blood are confirmed to be EGFR sensitive mutations (including exon 19 deletion or L858R).
  • There must be at least one measurable extracranial lesion that has not been locally treated at the time of enrollment.
  • Females should be using adequate contraceptive measures throughout the study; should not be breastfeeding at the time of screening, during the study and until 3 months after completion of the study; and must have a negative pregnancy test prior to start of dosing if of childbearing potential or must have evidence of non-childbearing potential by fulfilling 1 of the following criteria at Screening: a) Postmenopausal defined as age more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments. b) Women under 50 years old would be considered postmenopausal if they have been amenorrheic for 12 months or more, following cessation of exogenous hormonal treatments, and with luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in the postmenopausal range for the laboratory. c) Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy, but not by tubal ligation.
  • Male patients should be willing to use barrier contraception (i.e., condoms).
  • For inclusion in study, patient must provide a written informed consent.

Who cannot join

  • Treatment with any of the following: a) Prior treatment with systemic anti-cancer therapy for locally advancer or metastatic NSCLC including chemotherapy, biologic therapy, immunotherapy, or any investigational drug. b) Prior treatment with an EGFR TKI. c) Major surgery (excluding placement of vascular access) within 4 weeks of the first dose of study drug. d) Radiotherapy with a limited field of radiation for palliation within 4 week of the first dose of study drug, with the exception of patients receiving radiation to > 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug. e) Medications that are predominantly CYP3A4 strong inhibitors or inducers or sensitive substrates of CYP3A4 with a narrow therapeutic range within 7 days of the first dose of study drug.
  • Patients with other malignancies, except basal cell carcinoma and carcinoma in situ.
  • Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 at the time of starting study treatment, with the exception of alopecia and Grade 2, prior platinum-therapy related neuropathy.
  • Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension or active bleeding diatheses, which, in the Investigator's opinion, makes it undesirable for the patient to participate in the trial OR which would jeopardize compliance with the protocol such as active infection. Screening for chronic conditions is not required..
  • Refractory nausea, vomiting, or chronic gastrointestinal diseases, inability to swallow the study drug, or previous significant bowel resection that would preclude adequate absorption of Almonertinib.
  • Any of the following cardiac criteria: a) Mean resting corrected QT interval (QTc) > 470 ms obtained from 3 electrocardiograms (ECGs), using the screening clinic's ECG machine and Fridericia's formula for QT interval correction (QTcF). b) Any clinically important abnormalities in rhythm, conduction, or morphology of the resting ECG (e.g., complete left bundle branch block, third-degree heart block, second-degree heart block, PR interval > 250 ms). c) Any factors that increase the risk of QTc prolongation or risk of arrhythmic events, such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT interval. d) Left ventricular ejection fraction (LVEF)< 50%.
Show all 13Show fewer
  • Inadequate bone marrow reserve or organ function, as demonstrated by any of the following laboratory values: a) Absolute neutrophil count (ANC) <1.5×10^9 / L. b) Platelet count <100×10^9 / L. c) Hemoglobin <90 g/L (<9 g/dL). d) Alanine aminotransferase > 2.5 × upper limit of normal (ULN) if no demonstrable liver metastases or > 5 × ULN in the presence of liver metastases. e) Aspartate aminotransferase (AST) > 2.5 × ULN if no demonstrable liver metastases or > 5 × ULN in the presence of liver metastases. f) Total bilirubin (TBL) > 1.5 × ULN if no liver metastases or > 3 × ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinemia) or liver metastases. g) Creatinine > 1.5 × ULN concurrent with creatinine clearance < 50 mL/min (measured or calculated by the Cockcroft-Gault equation); confirmation of creatinine clearance is only required when creatinine is > 1.5 × ULN. h) ALB <28 g/L.
  • Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis that required steroid treatment, or any evidence of clinically active interstitial lung disease.
  • Women who are breastfeeding or have a positive urine or serum pregnancy test at the Screening Visit.
  • History of hypersensitivity to any active or inactive ingredient of Almonertinib, or to drugs with a similar chemical structure or class to Almonertinib.
  • Judgment by the Investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions, and requirements.
  • Any severe and uncontrolled ocular disease that may, in the ophthalmologist's opinion, present a specific risk to the patient's safety.
  • Any disease or condition that, in the opinion of the Investigator, would compromise the safety of the patient or interfere with study assessments.

Trial locations and contacts

1 site in 1 country.

Liu Anwen, PhD contact

+8613767120022

awliu666@163.com

Huang Long, PhD contact

+8613699549060

ndefy13211@ncu.edu.cn

China1 site

  • The Second Afiliated Hospital of Nanchang University

    Nanchang, Jiangxi, 330006

Other trials in China

About this study

Official title: Almonertinib Combined With Bevacizumab for EGFR-Mutant NSCLC Patients With Leptomeningeal Metastasis: A Prospective, Open-label, Multi-center, Single-arm Study

A prospective, open-label, multi-center, single-arm study of Almonertinib combined With Bevacizumab for EGFR-mutant NSCLC patients with leptomeningeal metastasis.

Read the detailed description

This is a prospective, open-label, multi-center, single-arm study to evaluate the efficacy and safety of Almonertinib combined with Bevacizumab for EGFR-mutant NSCLC patients with leptomeningeal metastasis. ALL patients were treated with Almonertinib 110mg oral daily and Bevacizumab 15mg/kg intravenous every 3 weeks. Study therapy continued until disease progression, unacceptable adverse event, or withdrawal of consent.

Being tested
Almonertinib, Bevacizumab
Keywords
Leptomeningeal Metastasis, Non-Small Cell Lung Cancer, EGFR Activating Mutation, Almonertinib, Bevacizumab
Medical subject headings
Meningeal Carcinomatosis, Carcinoma, Non-Small-Cell Lung

What participants receive

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

  • AlmonertinibDrug

    110 mg oral once daily

  • BevacizumabDrug

    15 mg/kg intravenous on Day 1 of 21 day cycles (every 3 weeks)

Study groups in NCT04944069
Study groupRoleWhat they receive
Almonertinib With BevacizumabExperimentalAlmonertinib 110 mg oral once daily with Bevacizumab 15 mg/kg intravenous on Day 1 of 21 day cycles (every 3 weeks)
Receives: Drug: Almonertinib; Drug: Bevacizumab

What is being measured

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

  1. Overall Survival (OS)

    OS is the time from the date of enrollment until death due to any cause

    Measured: From date of enrollment until the date of death, up to 2 years

Secondary outcomes (14)

  1. Time to Symptom Resolution

    Time to symptom resolution is the time from first drug dosage date (C1D1) until the date of symptom resolution

    Measured: From baseline, then every 3 weeks, up to 2 years

  2. Progression Free Survival (PFS)

    PFS is the time from date of enrollment until the date of PD (by investigator assessment) or death

    Measured: From baseline, then every 6 weeks, up to 2 years

  3. Objective Response Rate (ORR)

    ORR is the proportion of patients with a best overall response of complete response or partial response (CR+PR)

    Measured: From baseline, then every 6 weeks, up to 2 years

  4. Disease Control Rate (DCR)

    DCR is the proportion of patients with a best overall response of complete response, partial response or stable disease(CR+PR+SD)

    Measured: From baseline, then every 6 weeks, up to 2 years

  5. Duration of Response (DoR)

    DoR is the time from date of first documented response until the date of PD (by investigator assessment) or death

    Measured: From baseline, then every 6 weeks, up to 2 years

  6. Intracranial Progression Free Survival (iPFS)

    Intracranial progression-free survival

    Measured: From baseline, then every 6 weeks, up to 2 years

  7. Intracranial Objective Response Rate (iORR)

    Intracranial objective response rate

    Measured: From baseline, then every 6 weeks, up to 2 years

  8. Intracranial Disease Control Rate (iDCR)

    Intracranial disease control rate

    Measured: From baseline, then every 6 weeks, up to 2 years

  9. Intracranial Duration of Response (iDoR)

    Intracranial duration of response

    Measured: From baseline, then every 6 weeks, up to 2 years

  10. Extracranial Progression Free Survival (ePFS)

    Extracranial progression-free survival

    Measured: From baseline, then every 6 weeks, up to 2 years

  11. Extracranial Objective Response Rate (eORR)

    Extracranial objective response rate

    Measured: From baseline, then every 6 weeks, up to 2 years

  12. Extracranial Disease Control Rate (eDCR)

    Extracranial disease control rate

    Measured: From baseline, then every 6 weeks, up to 2 years

  13. Extracranial Duration of Response (eDoR)

    Extracranial duration of response

    Measured: From baseline, then every 6 weeks, up to 2 years

  14. Assess the safety of Almonertinib Combined With Bevacizumab

    Number of adverse events (AEs)/serious adverse events (SAEs)

    Measured: From baseline, then every 3 weeks, up to 2 years

Timeline

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

  1. First posted29 Jun 2021
  2. Study startJul 2021 (estimated)
  3. Primary completionMar 2024 (estimated)
  4. Study completionMar 2025 (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
Phase N/A
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
69 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04944069
Sponsor's protocol ID
HSM-10296-A016
Acronym
ATTRACT
Status last verified
May 2021
First submitted
26 May 2021
Last updated
29 Jun 2021
Results posted
No
Data monitoring committee
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

  • Liao BC, Lee JH, Lin CC, Chen YF, Chang CH, Ho CC, Shih JY, Yu CJ, Yang JC. Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors for Non-Small-Cell Lung Cancer Patients with Leptomeningeal Carcinomatosis. J Thorac Oncol. 2015 Dec;10(12):1754-61. doi: 10.1097/JTO.0000000000000669.

    PubMed 26334749

  • Li YS, Jiang BY, Yang JJ, Tu HY, Zhou Q, Guo WB, Yan HH, Wu YL. Leptomeningeal Metastases in Patients with NSCLC with EGFR Mutations. J Thorac Oncol. 2016 Nov;11(11):1962-1969. doi: 10.1016/j.jtho.2016.06.029. Epub 2016 Aug 15.

    PubMed 27539328

  • Wu YL, Ahn MJ, Garassino MC, Han JY, Katakami N, Kim HR, Hodge R, Kaur P, Brown AP, Ghiorghiu D, Papadimitrakopoulou VA, Mok TSK. CNS Efficacy of Osimertinib in Patients With T790M-Positive Advanced Non-Small-Cell Lung Cancer: Data From a Randomized Phase III Trial (AURA3). J Clin Oncol. 2018 Sep 10;36(26):2702-2709. doi: 10.1200/JCO.2018.77.9363. Epub 2018 Jul 30.

    PubMed 30059262

  • Yang JCH, Kim SW, Kim DW, Lee JS, Cho BC, Ahn JS, Lee DH, Kim TM, Goldman JW, Natale RB, Brown AP, Collins B, Chmielecki J, Vishwanathan K, Mendoza-Naranjo A, Ahn MJ. Osimertinib in Patients With Epidermal Growth Factor Receptor Mutation-Positive Non-Small-Cell Lung Cancer and Leptomeningeal Metastases: The BLOOM Study. J Clin Oncol. 2020 Feb 20;38(6):538-547. doi: 10.1200/JCO.19.00457. Epub 2019 Dec 6.

    PubMed 31809241

  • Saboundji K, Auliac JB, Perol M, Francois G, Janicot H, Marcq M, Dubos-Arvis C, Renault A, Guisier F, Odier L, Gervais R, Chouaid C. Efficacy of Osimertinib in EGFR-Mutated Non-Small Cell Lung Cancer with Leptomeningeal Metastases Pretreated with EGFR-Tyrosine Kinase Inhibitors. Target Oncol. 2018 Aug;13(4):501-507. doi: 10.1007/s11523-018-0581-2.

    PubMed 30039345

  • Nanjo S, Hata A, Okuda C, Kaji R, Okada H, Tamura D, Irie K, Okada H, Fukushima S, Katakami N. Standard-dose osimertinib for refractory leptomeningeal metastases in T790M-positive EGFR-mutant non-small cell lung cancer. Br J Cancer. 2018 Jan;118(1):32-37. doi: 10.1038/bjc.2017.394. Epub 2017 Nov 30.

    PubMed 29190637

  • Hu X, Chen W, Li X, Zhao C, Zhang C, Xiong F, Wu H. Clinical efficacy analysis of Osimertinib treatment for a patient with leptomeningeal metastasis of EGFR+ non-small cell lung cancer without the T790M mutation. Ann Palliat Med. 2019 Nov;8(5):525-531. doi: 10.21037/apm.2019.10.13.

    PubMed 31865717

  • Seto T, Kato T, Nishio M, Goto K, Atagi S, Hosomi Y, Yamamoto N, Hida T, Maemondo M, Nakagawa K, Nagase S, Okamoto I, Yamanaka T, Tajima K, Harada R, Fukuoka M, Yamamoto N. Erlotinib alone or with bevacizumab as first-line therapy in patients with advanced non-squamous non-small-cell lung cancer harbouring EGFR mutations (JO25567): an open-label, randomised, multicentre, phase 2 study. Lancet Oncol. 2014 Oct;15(11):1236-44. doi: 10.1016/S1470-2045(14)70381-X. Epub 2014 Aug 27.

    PubMed 25175099

  • Saito H, Fukuhara T, Furuya N, Watanabe K, Sugawara S, Iwasawa S, Tsunezuka Y, Yamaguchi O, Okada M, Yoshimori K, Nakachi I, Gemma A, Azuma K, Kurimoto F, Tsubata Y, Fujita Y, Nagashima H, Asai G, Watanabe S, Miyazaki M, Hagiwara K, Nukiwa T, Morita S, Kobayashi K, Maemondo M. Erlotinib plus bevacizumab versus erlotinib alone in patients with EGFR-positive advanced non-squamous non-small-cell lung cancer (NEJ026): interim analysis of an open-label, randomised, multicentre, phase 3 trial. Lancet Oncol. 2019 May;20(5):625-635. doi: 10.1016/S1470-2045(19)30035-X. Epub 2019 Apr 8.

    PubMed 30975627

  • Nakagawa K, Garon EB, Seto T, Nishio M, Ponce Aix S, Paz-Ares L, Chiu CH, Park K, Novello S, Nadal E, Imamura F, Yoh K, Shih JY, Au KH, Moro-Sibilot D, Enatsu S, Zimmermann A, Frimodt-Moller B, Visseren-Grul C, Reck M; RELAY Study Investigators. Ramucirumab plus erlotinib in patients with untreated, EGFR-mutated, advanced non-small-cell lung cancer (RELAY): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019 Dec;20(12):1655-1669. doi: 10.1016/S1470-2045(19)30634-5. Epub 2019 Oct 4.

    PubMed 31591063

Questions about this trial

What is this clinical trial studying?

A study testing Almonertinib and Bevacizumab in people with NSCLC and Leptomeningeal Metastasis, run by Second Affiliated Hospital of Nanchang University at 1 site in China.

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 8 inclusion and 13 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: status not confirmed, as of the sponsor's last update on 29 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

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.

Are results available for this study?

Results are not available in the source record.

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

Contact Liu Anwen, PhD (+8613767120022, awliu666@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 date of enrollment until the date of death, up to 2 years). 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 NCT04944069, which also lists 19 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 29 Jun 2021.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in