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Lung CancerPhase 2ACHIEVENCT04808752

Almonertinib as First-line Treatment in Patients With EGFR Mutations Positive in Advanced NSCLC With Brain Metastases

A Phase 2 study testing Almonertinib in people with Lung Cancer, run by Zhejiang Cancer Hospital 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 The sponsor has not verified this record for over two years, so it may be out of date.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
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Trial summary

This is a prospective, open-label, multi-center, single-arm clinical trial Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Lung Cancer
What is being tested?
Almonertinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
63 participants
Where
1 siteChina
Study dates
9 Jul 2021to 15 Jul 2024
Phase
Phase 2
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

  • Age from 18 to 75 years old.
  • Histology or cytology is confirmed to be NSCLC, imaging confirmed to be advanced NSCLC with brain metastasis (including relapsed or newly diagnosed advanced patients after previous surgical treatment; according to AJCC eighth edition lung cancer staging standards).
  • Tumor tissue samples or blood samples are confirmed to be EGFR sensitive mutations (including exon 19 deletion or L858R, both alone or coexist with other EGFR mutations). Tumor tissue is the first choice for examination; if the tumor tissue is not accessible or the patient cannot accept a tissue biopsy, a blood sample can be sent.
  • Have not received any systemic treatment. For patients who have received local treatment, the lesion within the scope of the local treatment cannot be used as the target lesion unless the lesion has progressed.
  • Patients are required to have a measurable extracranial lesion that has not undergone local treatment or has shown progression after local therapy, with a baseline longest diameter of at least 10 mm (or 15 mm for lymph nodes), and at least one intracranial lesion with a baseline longest diameter of at least 5 mm.
  • The brain condition is stable for at least 2 weeks before the study drug treatment, without any systemic (oral or parenteral) corticosteroid or anticonvulsant drug treatment. Non-absorbable corticosteroids can be used locally and inhaled according to the indications.
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  • The Eastern Cooperative Oncology Group (ECOG) physical status score is 0 or 1, and has not deteriorated at least 2 weeks before the study drug treatment, and the expected survival period is not less than 12 weeks.
  • Female patients of childbearing age are willing to take appropriate contraceptive measures and should not breastfeed from signing the informed consent to 6 months after the last study drug treatment; male patients are willing to take appropriate contraceptive measures from signing the informed consent to 6 months after the last study drug treatment Use barrier contraception (ie condoms).
  • Female patients of childbearing age must have a negative serum or urine HCG test within 7 days before enrollment in the study, and they must be non-lactating.
  • The subject voluntarily participated and signed an informed consent form in writing.

Who cannot join

  • Treatment with any of the following:
  • Previously received EGFR tyrosine kinase inhibitor (EGFR-TKI) treatment (such as erlotinib, gefitinib, icotinib, afatinib, osimertinib, and almonertinib, etc.) );
  • Within 4 weeks before the first administration of the study drug, the patient has undergone major surgery (such as craniotomy, thoracotomy, or laparotomy, etc.), or underwent minor traumatic surgery (biopsy, bronchoscopy, and Thoracic drainage). The definition of major surgery refers to the level 3 and level 4 surgery specified in the "Administrative Measures for the Clinical Application of Medical Technology" in Appendix H, which was implemented on November 1, 2018;
  • Except for patients who have received local radiotherapy (palliative bone radiotherapy for non-target lesions) within 2 weeks before the first administration of the study drug; within 4 weeks before the first administration of the study drug, more than 30% of the bone marrow has been irradiated (calculated area of the bone marrow) See Annex I), or received extensive radiotherapy; received whole brain radiotherapy due to this disease before enrollment;
  • Recurrence within 6 months after adjuvant or neoadjuvant treatment for early lung cancer; if there is both neoadjuvant therapy and adjuvant therapy, the adjuvant treatment time will be calculated;
  • Within 14 days before the first administration of the research drug, Chinese medicines and preparations with anti-tumor therapy or anti-tumor adjuvant therapy have been used (see Appendix E for the list of drugs);
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  • There is pleural effusion/peritoneal effusion that requires clinical intervention (patients who do not need to drain the effusion or who are stable for 2 weeks or more can be included in the group); there is pericardial effusion (a small amount of pericardium that is stable for 2 weeks or more) Fluid effusion is allowed to enter the group). If anti-tumor drugs have been used locally (such as chest cavity perfusion) during drainage, at least 5 drug half-lives or 21 days (whichever is shorter) must be eluted before the first administration of the study treatment before they can be included in the group;
  • Within 7 days before the first administration of the study drug, have used CYP3A4 strong inhibitors, strong inducers, or narrow therapeutic window drugs with sensitive substrates, or need to continue to receive these drugs during the study period (see Appendix E for the list of drugs);
  • Are receiving drugs that are known to prolong the QT interval or may cause torsades de pointes, or need to continue to receive these drugs during the study period (see Appendix E for the drug list and washout time);
  • The 5 half-lives of the study drug that participates in other clinical trials as a subject or is still in other clinical trials within 4 weeks before the first administration of the study drug, whichever is longer (except for screening failure).
  • Mixed SCLC and mixed NSCLC, large cell neuroendocrine carcinoma and sarcomatoid carcinoma confirmed by histology or cytology.
  • At the beginning of the study drug treatment, those with unresolved residual toxicity from previous anti-tumor therapy greater than CTCAE level 1, except for hair loss and level 2 neurotoxicity caused by previous anti-tumor. In the past, intracranial hemorrhage unrelated to the tumor occurred.
  • History of other primary malignant tumors, except for the following:
  • Malignant tumors that have been cured, have no activity for ≥5 years and have a very low risk of recurrence before being selected for the study;
  • Non-melanoma skin cancer or malignant freckle-like nevus that has been adequately treated and has no evidence of disease recurrence;
  • Carcinoma in situ with adequate treatment and no evidence of disease recurrence.
  • Diagnosis of meningeal metastasis through clinical symptoms or imaging or cerebrospinal fluid, or brain parenchymal metastasis combined with meningeal metastasis.
  • Patients who are allergic to MRI contrast agent gadolinium or who cannot tolerate MRI examinations (such as pacemakers, metals in the body, etc.).
  • As judged by the investigator, there are any serious or poorly controlled systemic diseases, such as poorly controlled hypertension, active bleeding-prone constitution, or active infection. No need to check for chronic diseases.
  • Clinically serious abnormal gastrointestinal function, which may affect the intake, transport or absorption of drugs, such as inability to take drugs orally, uncontrollable nausea or vomiting, history of extensive gastrointestinal resection, uncured recurrent diarrhea, atrophy Gastritis, uncured gastric diseases that require proton pump inhibitors for a long time, Crohn's disease, ulcerative colitis, etc.
  • Hepatic encephalopathy, hepatorenal syndrome or cirrhosis.
  • Meet any of the following cardiac examination results:
  • The average value of QT interval (QTcF) corrected by Fridericia's formula obtained from 3 ECG examinations at rest> 470 msec;
  • Resting ECG suggests that there are various clinically significant rhythms, conduction or ECG morphological abnormalities that are judged by the investigator (such as complete left bundle branch block, 3 degree atrioventricular block, 2 degree atrium Ventricular block and PR interval> 250 msec, etc.);
  • There are any factors that increase the risk of QTc prolongation or arrhythmia events, such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death or prolonged QT of immediate family members under 40 Any concomitant drugs in the interval;
  • Left ventricular ejection fraction (LVEF) <50%.
  • Insufficient bone marrow reserve or organ function, reaching any one of the following laboratory limits (no corrective treatment within 1 week before laboratory examination of blood draw):
  • Absolute neutrophil count <1.5×109 / L;
  • Platelet count <100×109 / L;
  • Hemoglobin <90 g/L (<9 g/dL);
  • If there is no clear liver metastasis, alanine aminotransferase> 2.5 times the upper limit of normal (ULN); if there is liver metastasis, alanine aminotransferase> 5×ULN;
  • If there is no clear liver metastasis, aspartate aminotransferase> 2.5×ULN; if there is liver metastasis, aspartate aminotransferase> 5×ULN;
  • If there is no clear liver metastasis, total bilirubin> 1.5×ULN; or Gilbert syndrome (unconjugated hyperbilirubinemia) or liver metastasis, total bilirubin> 3×ULN;
  • Creatinine>1.5×ULN and creatinine clearance rate<50 mL/min (calculated by Cockcroft-Gault formula); Only when creatinine>1.5×ULN, creatinine clearance rate needs to be confirmed;
  • Serum albumin (ALB) <28 g/L;
  • Active fungal, bacterial and/or viral infections requiring systemic treatment.
  • Female subjects who are pregnant, lactating, or planning to become pregnant during the study period.
  • A history of interstitial lung disease, a history of drug-induced interstitial lung disease, a history of radiation pneumonitis requiring steroid therapy, or any evidence of clinically active interstitial lung disease.
  • Have a history of hypersensitivity to any active or inactive ingredients of almonertinib or to drugs with similar chemical structure to almonertinib or the same class of almonertinib.
  • Any serious or uncontrolled eye disease (especially severe dry eye syndrome, dry keratoconjunctivitis, severe exposure keratitis or other diseases that may increase epithelial damage) may increase the safety of the patient by the doctor's judgment Sexual risk; or those with eye abnormalities that require surgery or are expected to require surgical treatment during the study period.
  • Patients who may have poor compliance with the procedures and requirements of the study as judged by the investigator, such as patients who have a clear history of neurological or mental disorders (including epilepsy or dementia), and currently suffer from mental disorders.
  • The investigator judges that there are any patients with conditions that endanger the safety of the patient or interfere with the evaluation of the study.

Trial locations and contacts

1 site in 1 country.

China1 site

  • Cancer Hospital Affiliated to University of Chinese Academy of Sciences

    Hangzhou, Zhejiang, 310000

Other trials in China

About this study

Official title: High-dose Almonertinib(HS-10296) as First-line Treatment in Patients With EGFR-sensitive Mutations in Advanced NSCLC With Brain Metastases: Prospective, Open-label, Multi-center, Single-arm Clinical Trial

This is a prospective, open-label, multi-center, single-arm clinical trial

Read the detailed description

This is a prospective, open-label, multi-center, single-arm clinical trial aimed at patients with advanced non-small cell lung cancer (NSCLC) with asymptomatic brain metastases with epidermal growth factor receptor sensitive mutations (EGFRm+) who have not received any systemic treatment To evaluate the effectiveness and safety of high-dose almonertinib mesylate.Eligible patients were included in the high-dose almonertinib treatment group and received oral almonertinib 165 mg once a day.

Conditions
Lung Cancer
Being tested
Almonertinib
Keywords
almonertinib
Medical subject headings
Lung Neoplasms

What participants receive

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

  • AlmonertinibDrug

    Also called Investigational Product

    Patients meeting the criteria for inclusion and exclusion were included in the high-dose almonertinib treatment group and received oral almonertinib 165 mg once a day.

Study groups in NCT04808752
Study groupRoleWhat they receive
Almonertinib high-dose groupExperimentalPatients who meet the criteria for inclusion and exclusion will be included in the high-dose almonertinib treatment group and receive oral almonertinib 165 mg once a day
Receives: Drug: Almonertinib

What is being measured

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

  1. PFS

    The PFS time is defined as time from enrollment to locoregional or systemic recurrence, second malignancy or death due to any cause; censored observations will be the last date of : "death", "last tumor assessment", "last follow up date" or "last date in drug log"

    Measured: 26 months

Secondary outcomes (9)

  1. iPFS

    iPFS is defined as the time from randomization to the first recording of the progress of intracranial disease or death from any cause.

    Measured: 26 months

  2. iORR

    The proportion of subjects whose intracranial lesions achieve Complete Response (CR) and Partial Response (PR) by the best response from the first dose of almonertinib to the end of study

    Measured: 26 months

  3. iDoR

    Number of days from the date that measurement criteria are first met for CR or PR (whichever status is recorded first) until the first subsequent date that progressive intracranial disease or death is documented.

    Measured: 26 months

  4. iDCR

    Intracranial disease control rate (iDCR) defined as the percentage of participants with Intracranial Disease Control best overall response (complete response, partial response or stable disease).

    Measured: 26 months

  5. ORR

    The proportion of subjects who achieve Complete Response (CR) and Partial Response (PR) by the best response from the first dose of almonertinib to the end of study.

    Measured: 26 months

  6. OS

    OS was defined as time from date of enrollment to date of death due to any cause. For participants still alive at the time of analysis, OS time was censored on last date that participants were known to be alive.

    Measured: Start of study drug to Survival Endpoint through study completion, an average of 4 years

  7. DoR

    Number of days from the date that measurement criteria are first met for CR or PR (whichever status is recorded first) until the first subsequent date that progressive disease or death is documented.

    Measured: 26 months

  8. DCR

    Disease Control Rate (DCR) defined as the percentage of participants with Disease Control best overall response (complete response, partial response or stable disease).

    Measured: 26 months

  9. Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

    To evaluate the security of high-dose almonertinib treatment in patients with EGFR mutations positive in advanced NSCLC with brain metastases

    Measured: 26 months

Timeline

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

  1. First posted22 Mar 2021
  2. Study start9 Jul 2021
  3. Primary completion15 Jun 2024 (estimated)
  4. Study completion15 Jul 2024 (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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
This is a open-label, multi-center, prospective, single-arm clinical trial
Masking
None (open label)
Enrolment
63 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04808752
Sponsor's protocol ID
YX-L-202107
Acronym
ACHIEVE
Status last verified
Apr 2024
First submitted
15 Mar 2021
Last updated
22 Apr 2024
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Li H, Chen K, Gong L, Qin J, Jin Y, Zhou R, Huang Z, Xu Y, Xu X, He J, Zhu J, Yu S, Lu H, Xu Y, Yu X, Han G, Chen J, Tan W, Lou G, Ren B, Chen X, Zhang D, Wang W, Shi X, Xie F, Zhao J, Han N, Li B, Fan Y. High-Dose Aumolertinib for Untreated EGFR-Variant Non-Small Cell Lung Cancer With Brain Metastases: The ACHIEVE Phase 2 Nonrandomized Clinical Trial. JAMA Oncol. 2025 Aug 1;11(8):900-908. doi: 10.1001/jamaoncol.2025.1779.

    PubMed 40569623

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Almonertinib in people with Lung Cancer, run by Zhejiang Cancer Hospital 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 10 inclusion and 42 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 22 Apr 2024. 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.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

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?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

PFS (time frame: 26 months). 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 NCT04808752, which also lists 1 linked publication.

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 22 Apr 2024.

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