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Non-Small Cell Lung Cancer (NSCLC)Phase 2NCT04905550

Almonertinib Combined With Cerebral Radiation Treat Brain Metastases From EGFR Positive NSCLC

A Phase 2 study testing Almonertinib and Stereotactic Radiotherapy(SRT) or Stereotactic Radiosurgery(SRS) or Whole-Brain Radiotherapy(WBRT) in people with Non-Small Cell Lung Cancer (NSCLC), run by Chongqing University 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 The sponsor has not verified this record for over two years, so it may be out of date.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
Search all trials

Trial summary

According to literature reports, about 16.3%-19% of newly diagnosed NSCLC patients are associated with brain metastasis, and 30%-50% of NSCLC patients will develop brain metastasis during the whole course of the disease. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Non-Small Cell Lung Cancer (NSCLC)
What is being tested?
Almonertinib and Stereotactic Radiotherapy(SRT) or Stereotactic Radiosurgery(SRS) or Whole-Brain Radiotherapy(WBRT)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
1 siteChina
Study dates
1 Mar 2021to 1 Aug 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 18-75 years old (calculated from the time when the subject signed the informed consent), both male and female.
  • Confirmed pathology of EGFR mutation positive（exon 19 deletion, L858R, T790M）NSCLC with brain metastases on enhanced MRI.
  • Subjects had not previously received chemotherapy, EGFR-TKI, biologic or immunotherapy, or other experimental therapy as first-line treatment for advanced NSCLC.
  • According to RECIST 1.1 criteria, subjects must have a measurable target lesion (maximum diameter under MRI/CT ≥10mm, short diameter of lymph node ≥15mm) that has been examined by CT or MRI.Tumor imaging evaluation was performed within 28 days prior to initial treatment.
  • ECOG PS score: 0-1 points.
  • Must be able to swallow tablets，and expected survival ≥3 months.
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  • Clinical diagnosis of Alzheimer's patients who can be treated with radiation therapy.
  • All screening laboratory tests are performed according to protocol and need to be performed within 14 days prior to the first dose.The values of laboratory tests performed by screening must meet the following criteria:
  • Routine blood examination :(no blood transfusion, no G-CSF, no drug correction within 14 days before screening)
  • Hemoglobin (Hb) ≥90 g/L;
  • Absolute neutrophil count (ANC) ≥1.5×109/L;
  • Platelet count (PLT) ≥100×109/L;
  • White blood cell count (WBC) ≥4.0×109/L and ≤15×109/L;
  • Biochemical test :(no blood transfusion or albumin within 14 days prior to screening)
  • AST and ALT ≤1.5×ULN (such as cancer that has spread to the liver, ≤5×ULN);
  • ALP≤2.5×ULN (such as tumor bone metastases, ≤5×ULN);
  • TBiL≤1.5×ULN.
  • ALB≥30 g/L;
  • Cr≤1.5×ULN, while creatinine clearance (CrCL)≥60 mL/min (Cockcroft - Gault formula);
  • APTT≤1.5×ULN, at the same time of INR or PT≤1.5×ULN (without anticoagulation therapy).
  • Women of childbearing age must have a serum pregnancy test within 3 days prior to the first dose and the results are negative.Women of reproductive age subjects and male subjects whose partners are women of reproductive age must agree to use barrier contraception (i.e., condoms) during the study period and for 180 days after the last administration of the study drug.
  • Volunteered to participate in clinical studies and signed informed consent.

Who cannot join

  • Exclusion criteria for target diseases:
  • Subjects who had previously received anti-EGFR-TKI therapy.
  • Patients with neuromeningeal disease but no intracranial metastases confirmed by MRI and/or CSF malignancy.
  • Previous radiotherapy for CNS metastases, including measurable or unmeasurable sites of the disease for efficacy assessment.
  • Patients who had undergone a major surgical procedure (other than placement of vascular access or CNS shunt) or had a major traumatic injury or were expected to require major surgery during the study period within 4 weeks prior to initial dosing.
  • Subject who can be surgically excised or treated with radical radiotherapy.
Show all 40Show fewer
  • History and complications:
  • The patient is using (or cannot be discontinued for at least 1 week prior to the first dosing of the investigational treatment) some drug or herbal supplement known to be a strong depressant or inducer of CYP3A4/5 (Appendix 8).
  • Excluding uncontrollable nausea and vomiting, chronic gastrointestinal disease, prior gastrectomy or other surgery, may affect the full absorption of the study drug.
  • exclude the presence of any serious or uncontrolled systemic disease or condition, including:
  • Uncontrolled high blood pressure, diabetes, thyroid disease;
  • Severe heart, lung or kidney disease;
  • Active bleeding constitution;
  • Any bacterial, viral, fungal or other active infection that the Investigator considers to pose a serious risk to the patient;
  • Active hepatitis (HBsAg positive or HBcAb positive, HBV DNA positive), or HCV antibody positive or HIV positive.
  • Patients with unstable symptomatic metastases: Any unstable and symptomatic CNS or distant metastases that were not controlled by previous surgery, radiotherapy, or corticosteroid treatment within 2 weeks prior to the initial study treatment.Corticosteroids were used before treatment for CNS symptoms, but the symptoms were controllable after treatment, and corticosteroids were used during radiotherapy.
  • Exclude subjects who are participating in other clinical studies or whose first administration has been less than 3 weeks (or 5 half-lives of the investigational drug) since the end of the previous clinical study (last dosing).
  • Excluding subjects who expected to require any other form of antitumor therapy (including maintenance therapy with other NSCLC drugs, and/or surgical resection) during the study.
  • excluded subjects with high suspicion of interstitial pneumonia; Or subjects that may interfere with the detection or management of suspected drug-related pulmonary toxicity;Or other moderate to severe lung diseases that seriously affect lung function.
  • Subjects with other active malignancies requiring concurrent treatment were excluded.
  • Subjects with a previous history of malignancy were excluded unless they had achieved a complete response at least 5 years prior to screening and did not require or are not expected to require additional treatment during the study period for basal cell carcinoma of the skin, superficial bladder carcinoma, squamous cell carcinoma of the skin, or cervical carcinoma in situ.Rule out with Ⅱ magnitude myocardial ischemia and myocardial infarction, arrhythmia of the subjects of poor control.
  • Ruled out according to the NYHA standard Ⅲ ~ Ⅳ level cardiac insufficiency or heart colour to exceed examination: LVEF, left ventricular ejection fraction < 50% of the subjects.
  • Patients with significant hemoptysis or hemoptysis of half a teaspoon (2.5ml) or more per day within 1 month before randomization.
  • Patients with bleeding symptoms of significant clinical significance or with definite bleeding tendency, such as gastrointestinal bleeding, hemorrhagic gastric ulcer, or vasculitis, occurred within 1 month prior to randomization.
  • Artery/venous thrombosis events occurred in the first 3 months at random, such as cerebrovascular accidents (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep venous thrombosis and pulmonary embolism, etc.
  • Subjects with active tuberculosis (TB) were excluded.In subjects suspected of active TB, chest X-rays and sputum should be examined, and clinical signs and symptoms should be excluded.Subjects with a history of active tuberculosis infection within the previous 1 year were screened, even if they had been treated. Subjects with a history of active TB infection more than 1 year ago should also be excluded unless the course and type of anti-TB treatment previously used is demonstrated to be appropriate.
  • Excluding subjects who were preparing for or had previously received tissue/organ transplants.
  • Subjects who received or will receive live vaccine within 30 days prior to the first dose were excluded.
  • Inclusion of subjects with uncontrolled tumor-related pain is not recommended.Subjects requiring pain medication must have a stable pain control regimen;Symptomatic lesions suitable for palliative radiotherapy (such as bone metastases or nerve invasion metastases) should be completed at least 2 weeks before inclusion; Asymptomatic metastatic foci whose further growth may result in dysfunction or intractable pain (e.g. epidural metastases that do not show spinal cord compression) should be considered for local-regional treatment before randomization, if appropriate.
  • Physical examination and laboratory examination
  • A known history of positive human immunodeficiency virus (HIV) tests or a known history of acquired immunodeficiency syndrome (AIDS).
  • Untreated active hepatitis:
  • Hepatitis B: HBV surface antigen (HBV sAg) positive and HBV DNA detection value is higher than the upper limit of normal value;
  • Hepatitis C: Hepatitis C virus antibody (HCV Ab) positive, HCV RNA positive, and abnormal liver function;
  • Complicated with hepatitis B and C co-infection.
  • Exclude subjects with uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage.
  • Allergic reactions and adverse drug reactions:Study drugs with CYP3A4 inhibition agents, inducers, or drugs with a narrow therapeutic window that are CYP3A4-sensitive substrates were used within 7 days before the first administration.
  • Patients receiving concurrent chemotherapy were excluded.
  • Excludes subjects with mental illness, alcoholism, inability to quit smoking, drug or substance abuse.
  • At the discretion of the Investigator, exclude subjects with history or current evidence of any disease, treatment or laboratory anomaly that may confuse study results, interfere with subjects' participation in the study procedure, or is not in the best interest of subjects' participation in the study.

Trial locations and contacts

1 site in 1 country.

Dingyi Yang, M.D. contact

15123117697

dingyiyang@cqu.edu.cn

Ying Wang, Ph.D, M.D. contact

13996412826

yingwang197011@163.com

China1 site, 1 recruiting

  • Chongqing University Cancer Hospital

    Chongqing, Chongqing Municipality, 400030

    Dingyi Yang, M. D., 15123117697, dingyiyang@cqu.edu.cn

    Ying Wang, Ph.D, M. D., 13996412826, yingwang197011@163.com

    Recruiting

Other trials in China

About this study

Official title: An Exploratory Clinical Study of Almonertinib in Combination With Craniocerebral Radiotherapy in First-line Treatment of EGFR Positive Non-Small Cell Lung Cancer(NSCLC) With Brain Metastases

According to literature reports, about 16.3%-19% of newly diagnosed NSCLC patients are associated with brain metastasis, and 30%-50% of NSCLC patients will develop brain metastasis during the whole course of the disease.

Patients with EGFR positive-type had a 10-15% higher risk of brain metastasis than patients with EGFR wild-type. mOS in patients with EGFR positive were twice as high as those with EGFR wild-type, despite the presence of brain metastasis.

Read more

Improving the control rate of intracranial lesions in patients with EGFR positive can not only improve the quality of life, but also may translate into survival benefits and improve OS. Previous studies have shown that in lung cancer patients with EGFR-sensitive mutations, craniocerebral radiotherapy prior to delayed craniocerebral radiotherapy significantly prolonged OS.

The first-line treatment of the third generation of EGFR-TKI targeting drug Almonertinib for EGFR-positive NSCLC can eliminate the possible EGFR T790M mutant clones at an early stage and better control the disease progression. Moreover, Almonertinib is easy to pass through the blood-brain barrier, which can not only better control intracranial lesions, but also control, prevent or delay the occurrence of brain metastasis.

This study was intended to conduct a randomized controlled study on the safety and efficacy of early craniocerebral radiotherapy combined with Almonertinib in patients with EGFR positive non-small cell lung cancer with brain metastasis.

Through the above studies we hope to confirm that early craniocerebral radiotherapy combined with Almonertinib is safe and feasible for patients with EGFR positive newly diagnosed with brain metastasis, and can prolong the intracranial progression-free survival (IPFS), and even extend the progression-free survival (PFS) and overall survival (OS).

Read the detailed description

All eligible patients will receive craniocerebral radiotherapy in combination with Almonertinib.

Here are two types of craniocerebral radiotherapy:

  1. SRS or SRT is recommended for patients with ≤4 intracranial metastases and the maximum lesion ≤4cm. 24-15 Gy*1F was recommended if use SRS. 9-12 Gy*3F or 6Gy×5F was recommended if use SRT.
  2. For >4 intracranial metastases, or the maximum lesion>4cm, whole-brain radiotherapy (WBRT) of 30Gy/10F was recommended, and then the large residual lesions will be treated with a local dose (≤DT 45Gy/15F). Hippocampal protection is highly recommended.
Being tested
Almonertinib, Stereotactic Radiotherapy(SRT) or Stereotactic Radiosurgery(SRS) or Whole-Brain Radiotherapy(WBRT)
Keywords
Almonertinib, Radiotherapy, Brain Metastasis, Non-Small Cell Lung Cancer, Intracranial Progress Free Survival
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Brain Neoplasms

What participants receive

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

  • AlmonertinibDrug

    Also called The third generation of EGFR - TKI

    Almonertinib 110mg p.o qd. Treatment with Almonertinib will continue until progression or unacceptable toxicity.

  • Stereotactic Radiotherapy(SRT) or Stereotactic Radiosurgery(SRS) or Whole-Brain Radiotherapy(WBRT)Radiation

    Image guided, 24-15 Gy*1F was recommended if use SRS. 9-12 Gy*3F/1W or 6Gy×5F/1W was recommended if use SRT. 30Gy/10F/2W for WBRT, large residual lesions will be treated with a local dose (≤DT 45Gy/15F).

Study groups in NCT04905550
Study groupRoleWhat they receive
Craniocerebral radiotherapy combined with Almonertinib 110mg p.o qdExperimentalAlmonertinib mesylate tablet, 110mg, qd; until the disease progresses or unacceptable toxicity. The craniocerebral radiotherapy was acceptable from 1 week before to 6 weeks after treatment with Almonertinib. Dose adjustment and delay of Almonertinib are allowed. Delay of Almonertinib is allowed for up to 9 weeks, calculated from the time of last administration, otherwise, treatment is terminated.
Receives: Drug: Almonertinib; Radiation: Stereotactic Radiotherapy(SRT) or Stereotactic Radiosurgery(SRS) or Whole-Brain Radiotherapy(WBRT)

What is being measured

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

  1. Intracranial Progress Free Survival(iPFS)

    As determined by the investigator using RECIST 1.1 criteria between patients receiving Almonertinib and craniocerebral radiotherapy. iPFS is defined as The time between the start of treatment and the observation of progression of intracranial lesions or death from any cause. In order to ascertain this endpoint, efforts will be made so that patients will be followed for 156 weeks or until progression of disease (and treatment cessation), whichever comes first. At each time-point, subjects should have CT/MR of chest and head with contrast.

    Measured: Up to 4 years

Secondary outcomes (5)

  1. Number of adverse events of grade 3-4 or higher

    To estimate and compare rates of ≥ grade 3-4 adverse events, by organ system, by CTCAEv4.0 that occur within 3 months from the start of craniocerebral radiotherapy when given prior to or concurrently with Almonertinib.

    Measured: Up to 4 years

  2. Rate of long term adverse events

    To estimate and compare the rates of long-term adverse events (after 3 months) from the end of craniocerebral radiotherapy when given prior to or concurrently with Almonertinib.

    Measured: Up to 4 years

  3. Rate of change in tumor microenvironment

    To evaluate and compare changes in the tumor microenvironment induced by radiation when given prior to or concurrently with Almonertinib.

    Measured: Up to 4 years

  4. Changes in EGFR mutations

    To evaluate whether response to therapy correlates with changes in EGFR mutations among patients treated with Almonertinib combined with craniocerebral radiotherapy.

    Measured: Up to 4 years

  5. Overall Survival

    Time from entry to death from any cause (the last follow-up time for patients lost to follow-up; Patients who were still alive at the end of the study, the end date of follow-up).

    Measured: Up to 4 years

Timeline

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

  1. First posted27 May 2021
  2. Study start1 Mar 2021
  3. Primary completion1 Mar 2024 (estimated)
  4. Study completion1 Aug 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
Masking
None (open label)
Enrolment
50 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04905550
Sponsor's protocol ID
RadiAl-CNS
Status last verified
May 2021
First submitted
23 May 2021
Last updated
2 Jun 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Nagasaka M, Zhu VW, Lim SM, Greco M, Wu F, Ou SI. Beyond Osimertinib: The Development of Third-Generation EGFR Tyrosine Kinase Inhibitors For Advanced EGFR+ NSCLC. J Thorac Oncol. 2021 May;16(5):740-763. doi: 10.1016/j.jtho.2020.11.028. Epub 2020 Dec 15.

    PubMed 33338652

  • Dong RF, Zhu ML, Liu MM, Xu YT, Yuan LL, Bian J, Xia YZ, Kong LY. EGFR mutation mediates resistance to EGFR tyrosine kinase inhibitors in NSCLC: From molecular mechanisms to clinical research. Pharmacol Res. 2021 May;167:105583. doi: 10.1016/j.phrs.2021.105583. Epub 2021 Mar 26.

    PubMed 33775864

  • Wakuda K, Yamaguchi H, Kenmotsu H, Fukuda M, Takeshita M, Suetsugu T, Kirita K, Ebi N, Hataji O, Miura S, Chibana K, Okamoto I, Yoshimura K, Nakagawa K, Yamamoto N, Sugio K. A phase II study of Osimertinib for patients with radiotherapy-naive CNS metastasis of non-small cell lung cancer: treatment rationale and protocol design of the OCEAN study (LOGIK 1603/WJOG 9116L). BMC Cancer. 2020 May 1;20(1):370. doi: 10.1186/s12885-020-06874-6.

    PubMed 32357848

  • Franchino F, Ruda R, Soffietti R. Mechanisms and Therapy for Cancer Metastasis to the Brain. Front Oncol. 2018 May 24;8:161. doi: 10.3389/fonc.2018.00161. eCollection 2018.

    PubMed 29881714

  • Nishino M, Soejima K, Mitsudomi T. Brain metastases in oncogene-driven non-small cell lung cancer. Transl Lung Cancer Res. 2019 Nov;8(Suppl 3):S298-S307. doi: 10.21037/tlcr.2019.05.15.

    PubMed 31857953

  • Nieder C, Norum J, Dalhaug A, Aandahl G, Pawinski A. Radiotherapy versus best supportive care in patients with brain metastases and adverse prognostic factors. Clin Exp Metastasis. 2013 Aug;30(6):723-9. doi: 10.1007/s10585-013-9573-x. Epub 2013 Feb 8.

    PubMed 23392634

  • Andrews DW, Scott CB, Sperduto PW, Flanders AE, Gaspar LE, Schell MC, Werner-Wasik M, Demas W, Ryu J, Bahary JP, Souhami L, Rotman M, Mehta MP, Curran WJ Jr. Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trial. Lancet. 2004 May 22;363(9422):1665-72. doi: 10.1016/S0140-6736(04)16250-8.

    PubMed 15158627

  • Chang JY, Bezjak A, Mornex F; IASLC Advanced Radiation Technology Committee. Stereotactic ablative radiotherapy for centrally located early stage non-small-cell lung cancer: what we have learned. J Thorac Oncol. 2015 Apr;10(4):577-85. doi: 10.1097/JTO.0000000000000453.

    PubMed 25514807

  • Gomez DR, Blumenschein GR Jr, Lee JJ, Hernandez M, Ye R, Camidge DR, Doebele RC, Skoulidis F, Gaspar LE, Gibbons DL, Karam JA, Kavanagh BD, Tang C, Komaki R, Louie AV, Palma DA, Tsao AS, Sepesi B, William WN, Zhang J, Shi Q, Wang XS, Swisher SG, Heymach JV. Local consolidative therapy versus maintenance therapy or observation for patients with oligometastatic non-small-cell lung cancer without progression after first-line systemic therapy: a multicentre, randomised, controlled, phase 2 study. Lancet Oncol. 2016 Dec;17(12):1672-1682. doi: 10.1016/S1470-2045(16)30532-0. Epub 2016 Oct 24.

    PubMed 27789196

  • Garon EB, Siegfried JM, Stabile LP, Young PA, Marquez-Garban DC, Park DJ, Patel R, Hu EH, Sadeghi S, Parikh RJ, Reckamp KL, Adams B, Elashoff RM, Elashoff D, Grogan T, Wang HJ, Dacic S, Brennan M, Valdes Y, Davenport S, Dubinett SM, Press MF, Slamon DJ, Pietras RJ. Randomized phase II study of fulvestrant and erlotinib compared with erlotinib alone in patients with advanced or metastatic non-small cell lung cancer. Lung Cancer. 2018 Sep;123:91-98. doi: 10.1016/j.lungcan.2018.06.013. Epub 2018 Jun 22.

    PubMed 30089602

  • Yang JC, Camidge DR, Yang CT, Zhou J, Guo R, Chiu CH, Chang GC, Shiah HS, Chen Y, Wang CC, Berz D, Su WC, Yang N, Wang Z, Fang J, Chen J, Nikolinakos P, Lu Y, Pan H, Maniam A, Bazhenova L, Shirai K, Jahanzeb M, Willis M, Masood N, Chowhan N, Hsia TC, Jian H, Lu S. Safety, Efficacy, and Pharmacokinetics of Almonertinib (HS-10296) in Pretreated Patients With EGFR-Mutated Advanced NSCLC: A Multicenter, Open-label, Phase 1 Trial. J Thorac Oncol. 2020 Dec;15(12):1907-1918. doi: 10.1016/j.jtho.2020.09.001. Epub 2020 Sep 9.

    PubMed 32916310

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Almonertinib and Stereotactic Radiotherapy(SRT) or Stereotactic Radiosurgery(SRS) or Whole-Brain Radiotherapy(WBRT) in people with Non-Small Cell Lung Cancer (NSCLC), run by Chongqing University 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 22 inclusion and 40 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 2 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.

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?

Contact Dingyi Yang, M.D. (15123117697, dingyiyang@cqu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Intracranial Progress Free Survival(iPFS) (time frame: Up to 4 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 NCT04905550, which also lists 11 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 2 Jun 2021.

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