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NeurocognitivePhase 2NCT04829019

Neurocognition in NSCLC Patients Treated With Osimertinib or Osimertinib + WBI

A Phase 2 study testing Osimertinib and whole-brain irradiation and Osimertinib in people with Neurocognitive, run by Sun Yat-sen 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 The sponsor has not verified this record for over two years, so it may be out of date.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
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Trial summary

This is a prospective, randomised, positive-controlled, study to assess the neurocognitive function of upfront Osimertinib compared to whole-brain irradiation (WBI) plus Osimertinib in EGFR-mutant (Ex 19Del and L858R) NSCLC patients with symptomatic brain metastases, as well as the efficacy and safety. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Neurocognitive
What is being tested?
Osimertinib and whole-brain irradiation and Osimertinib
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
88 participants
Where
1 siteChina
Study dates
7 Apr 2021to 31 Oct 2025
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Provision of informed consent prior to any study specific procedures
  • Male or female, aged at least 18 years
  • Eastern Cooperative Oncology Group (ECOG) performance-status score of 0 or 1
  • Life expectancy of at least 3 months
  • Histologically or cytologically documented metastatic NSCLC, which are not amenable to curative surgery or radiotherapy, patients must be classified as stage IIIB-IV. Staging will be according to the TNM staging system for lung cancer (8th edition)
  • Histologically documented that with sensitizing EGFR mutations(either L858R or Exon19del)
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  • symptomatic brain metastasis, with at least three metastatic lesions in the brain which need WBI based on investigator's decision. Symptom score 1-6 point.(notes: Symptomatic definition: Symptoms without acute intervention or hospitalization, symptoms including but not limited in headache, nausea, dizziness, and sensory disturbance, but without hospitalization or medical emergency.)
  • HVLT-R score 15 point (Notes: this number is based on the data in a study in Chinese population)
  • At least 1 measurable lesion in the brain according to RECIST 1.1; At least one lesion, not previously irradiated, that can be accurately measured at baseline as ≥ 10 mm in the longest diameter with computed tomography (CT) or magnetic resonance imaging (MRI).
  • No previous treatment with EGFR-TKI or other systemic treatment, as well as radiotherapy for brain metastases.
  • Female subjects should be using highly effective contraceptive measures, and must have a negative pregnancy test and not be breast-feeding prior to start of dosing if of child-bearing potential, or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening:
  • Post-menopausal defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments
  • 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 LH and FSH levels in the post-menopausal range for the institution
  • Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation Further information in Appendix E(Definition of Women of Childbearing Potential and Acceptable Contraceptive Methods)
  • Male subjects should be willing to agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating sperm, as defined below: a. With female partners of childbearing potential or pregnant female partners, men must remain abstinent or use a condom during the treatment period and for at least 4 months after the last dose of Osimertinib. b. Men must refrain from donating sperm during this same period

Who cannot join

  • Involvement in the planning and/or conduct of the study (applies to both Investigator staff and/or staff at the study site)
  • Previous randomisation in the present study or previous treatment with osimertinib
  • Leptomeningeal met alone or synchronously is not allowed
  • History of hypersensitivity to active or inactive excipients of Osimertinib or drugs with similar chemical structure or class to Osimertinib
  • For patients, inability to collect plasma, CSF and tissue at baseline
  • Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, which in the investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardise compliance with the protocol, or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV). Screening for chronic conditions is not required.
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  • Currently receiving (or unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be strong inducers of CYP3A4 (at least 3 week prior) (Appendix D). All patients must try to avoid concomitant use of any medications, herbal supplements and/or ingestion of foods with known inducer effects on CYP3A4.
  • Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of osimertinib.
  • Any of the following cardiac criteria:
  • Mean resting corrected QT interval (QTc) > 470 msec obtained from 3 electrocardiograms (ECGs), using the screening clinic ECG machine derived QTc value (Note: patients with congenital long QT syndrome (CLQTS) are excluded from this study.)
  • Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG e.g. complete left bundle branch block, third degree heart block and second degree heart block.
  • Patient with any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, electrolyte abnormalities (including: Serum/plasma potassium < LLN; Serum/plasma magnesium < LLN; Serum/plasma calcium < LLN) , 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 and cause Torsades de Pointes
  • Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease.
  • Inadequate bone marrow reserve or organ function (as demonstrated by any of the following laboratory values:
  • Absolute neutrophil count <1.5 x 109/L;
  • Platelet count <100 x 109/L;
  • Haemoglobin <90 g/L;
  • Alanine aminotransferase >2.5 x ULN if no demonstrable liver metastases or >5 times ULN in the presence of liver metastases;
  • Aspartate aminotransferase >2.5 x ULN if no demonstrable liver metastases or >5 times ULN in the presence of liver metastases;
  • Total bilirubin >1.5 x ULN if no liver metastases or >3 x ULN in the presence of documented Gilbert's Syndrome [unconjugated hyperbilirubinaemia] or liver metastases;
  • Serum creatinine >1.5 x ULN concurrent with creatinine clearance <50 mL/min [measured or calculated by Cockcroft and Gault equation]
  • 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.
  • Women who are pregnant or breast-feeding.

Trial locations and contacts

1 site in 1 country.

Li Zhang contact

+8602087343822

zhangli@sysucc.org.cn

Yunpeng Yang contact

+8613928791406

yangyp@sysucc.org.cn

China1 site, 1 recruiting

  • Department of Medical Oncology, Cancer Center of Sun Yat-Sen University

    Guangzhou, Guangdong, 510060

    Yunpeng Yang, +8613928791406, yangyp@sysucc.org.cn

    Recruiting

Other trials in China

About this study

Official title: A Randomised Controlled Trial to Investigate the Neurocognition in EGFR-mutant Advanced Non-small Cell Lung Cancer Patients With Symptomatic Brain Metastases Treated With Osimertinib or Osimertinib Plus Whole-brain Irradiation (WBI)

This is a prospective, randomised, positive-controlled, study to assess the neurocognitive function of upfront Osimertinib compared to whole-brain irradiation (WBI) plus Osimertinib in EGFR-mutant (Ex 19Del and L858R) NSCLC patients with symptomatic brain metastases, as well as the efficacy and safety.

Read the detailed description

Account for patients with wild type EGFR, sample attrition , incidence rate of symptomatic brain metastasis(10%) and any other reasons for screen failure rate(50%), it is esimated that 88 patients will be randomized from 5 sites. Patients will be randomized 1:1, the experimental arm is upfront Osimertinib with WBI sequential therapy, while the control arm is Osimertinib plus WBI. Osimertinib at a dose of 80 mg once per day, until unacceptable adverse events or disease progression occurred. WBI could be given to patients in experimental arm at any time base on investigator's decision after treatment initiated. Patients will be stratifed at randomization by GPA score (3.5-4 vs <3.5) and the mutation type (Ex19Del / L858R). Patients will undergo the neurocognition, efficacy and safety assessments at baseline, and every 8 weeks until treatment is completed or discontinued. About time to brain metastases symptoms deterioration, the assessment was repeated in the first week (on site), second week (through telephone) and fourth week (on site). The rest assessment will be as well as other evaluations repeated every 8 weeks. To evaluate the correlation and predictive or prognostic value between gene dynamic changes and clinical efficacy, the tissue, plasma and cerebrospinal fluid (CSF) samples will be collected at baseline. CSF will be collected in patients with intracranial progression. Plasma will be collected in all the patients at disease progression, while tissue is optional. Also, plasma will be collected at week 8(first evaluation of efficacy).

Conditions
Neurocognitive
Being tested
Osimertinib and whole-brain irradiation, Osimertinib

What participants receive

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

  • Osimertinib and whole-brain irradiationRadiation

    Osimertinib at a dose of 80 mg once per day, and WBI

  • OsimertinibDrug

    Osimertinib at a dose of 80 mg once per day, until unacceptable adverse events or disease progression occurred. WBI could be given to patients in experimental arm at any time base on investigator's decision after treatment initiated.

Study groups in NCT04829019
Study groupRoleWhat they receive
whole-brain irradiation (WBI) plus OsimertinibActive comparatorOsimertinib plus WBI, with Osimertinib at a dose of 80 mg once per day.
Receives: Radiation: Osimertinib and whole-brain irradiation
OsimertinibActive comparatorOsimertinib with WBI sequential therapy, with Osimertinib at a dose of 80 mg once per day.
Receives: Drug: Osimertinib

What is being measured

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

  1. neurocognitive function (HVLT-R)

    measured as a significant deterioration (5-point drop compared with baseline) in Hopkins Verbal Learning Test-Revised (HVLT-R) total recall at 4 months

    Measured: at 4 months

Secondary outcomes (9)

  1. intracranial progression-free survival

    defined as the time from randomization to the date of intracranial disease progression

    Measured: assessed up to 36 months

  2. progression-free survival

    defined as the time from randomization to the date of first documentary disease progression

    Measured: assessed up to 36 months

  3. intracranial overall response rate

    percentage of participants with objective response in brain metastasis

    Measured: assessed up to 60 months

  4. overall response rate

    percentage of participants with objective response

    Measured: assessed up to 60 months

  5. intracranial disease control rate

    percentage of participants with disease control in brain metastasis

    Measured: assessed up to 60 months

  6. disease control rate

    percentage of participants with disease control

    Measured: assessed up to 60 months

  7. intracranial Duration of Response

    defined as the time from randomization to the date of first documentary PR or CR in brain metastasis

    Measured: assessed up to 60 months

  8. Duration of Response

    defined as the time from randomization to the date of first documentary PR or CR

    Measured: assessed up to 60 months

  9. Time to initiate WBI

    defined as the time from randomization to the date of initiate WBI

    Measured: assessed up to 36 months

Timeline

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

  1. First posted2 Apr 2021
  2. Study start7 Apr 2021 (estimated)
  3. Primary completion1 Apr 2024 (estimated)
  4. Study completion31 Oct 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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
88 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04829019
Sponsor's protocol ID
ESR-18-14285
Status last verified
Mar 2021
First submitted
31 Mar 2021
Last updated
2 Apr 2021
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Osimertinib and whole-brain irradiation and Osimertinib in people with Neurocognitive, run by Sun Yat-sen 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 15 inclusion and 23 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 Apr 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 Li Zhang (+8602087343822, zhangli@sysucc.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

neurocognitive function (HVLT-R) (time frame: at 4 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 NCT04829019.

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 Apr 2021.

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