Non-small Cell Lung Cancer Confirmed by Histopathology or CytologyNCT05497076
the Efficacy and Safety of Dalpiciclib Combined With Third-generation EGFR-TKI in Patients With EGFR Mutation and Meningial Metastasis in Non-small Cell Lung Cancer Progressing Through Third-generation TKI and Platinum-containing Two-drug Chemotherapy
An observational study of Non-small Cell Lung Cancer Confirmed by Histopathology or Cytology and The TNM (8th) Phase is IV, run by Fujian Cancer Hospital.
Trial summary
Efficacy and safety of Dalpiciclib combined with third-generation EGFR-TKI in patients with advanced EGFR-mutated non-small cell lung cancer with meningeal metastasis after third-generation TKI and platinum-containing chemotherapy Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-small Cell Lung Cancer Confirmed by Histopathology or Cytology, The TNM (8th) Phase is IV, With EGFR Mutations
- How many people
- 9 participants
- Where
- No sites listed yet
- Study dates
- 1 Sep 2022to 1 Jul 2024
- Phase
- Observational
- 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
Study population: Non-small cell lung cancer diagnosed by histopathology or cytology, TNM (8th) stage IV, accompanied by EGFR mutation, meningeal progression after previous platinum-containing two-drug chemotherapy and third-generation EGFR-TKI treatment, male and female, age ≥18 years, ECOG PS score 0-2
Who may be able to join
- Age ≥18 when signing informed consent, both male and female;
- Advanced or metastatic NSCLC confirmed by histology or cytology is stage IV according to THE TNM stage of lung cancer, IASLC 2015 Eighth Edition;
- EgFR-sensitive mutations (exon 19 deletion, exon 21 L858R or L861Q mutation, exon 18 G719X mutation, etc.) exist. Meningeal progression follows platinum-containing chemotherapy in combination with/without antivascular and/or in combination with/without immunotherapy, and 3 generations of EGFR-TKI (which can be 1+3, 2+3 or directly after 3 generations of targeted therapy). Patients with BMS can be treated with brain radiotherapy. Cerebrospinal fluid and peripheral blood were collected for EXPLORATORY NGS testing. Subjects identified with cdK4/6, CDKN2A, CDKN2B, CCND1 (Cyclin D1), CCND2 (Cyclin D2), CCND3 (Cyclin D3), CCNE1 and RB1 cell cycle pathway changes by genetic testing were stratified for analysis;
- ECOG PS score: 0-2;
- Normal function of major organs, that is, meeting the following criteria: a) blood routine examination (no blood transfusion within 14 days, no hematopoietic stimulation drugs correction) : Hemoglobin (Hb) ≥90g/L; Absolute neutrophil count (ANC) ≥1.5×109/L; Platelet (PLT) ≥100×109/L; White blood cell count (WBC) ≥3.0×109/L; B) Biochemical examination: ALT and AST ≤2.5× upper limit of normal value (ULN); Serum total bilirubin (TBIL) ≤1.5×ULN; Serum creatinine (Cr) ≤1.5×ULN or creatinine clearance ≥50ml/min; If liver metastasis was present, total bilirubin ≤3×ULN, ALT and AST≤5×ULN; C) Coagulation function: activated partial thrombin time (APTT), international standardized ratio (INR), prothrombin time (PT) ≤1.5×ULN; D) Doppler ultrasound assessment: left ventricular ejection fraction (LVEF)≥50%;
- a washout period of at least 21 days between the last dose of chemotherapy and enrollment (if the patient did not receive radiotherapy); Patients undergoing brain radiation therapy must complete and fully recover from the acute toxicity of radiation therapy. A washout period of at least 14 days is required between the end of radiotherapy and enrollment.
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- The expected survival time is not less than 3 months;
- Allow asymptomatic BMS who are stable and do not require steroid treatment for more than 4 weeks before the study begins;
- Patient can swallow oral medication;
- Women of childbearing age must have a negative pregnancy test (serum or urine) within 14 days prior to enrollment and voluntarily use an appropriate method of contraception during the observation period and within 3 months after the last administration of the study drug; For men, surgical sterilization or consent to use appropriate methods of contraception during the observation period and for 3 months after the last administration of the study drug; The patients voluntarily participated in the study and signed the informed consent (or legal representative signed). It is expected that the patients have good compliance and can cooperate with the study according to the protocol requirements;
Who cannot join
- Second-line or above chemotherapy or other anti-tumor drugs;
- Cerebral edema requiring hormone dehydration treatment;
- Major surgery performed within 4 weeks prior to the start of the study treatment or planned to be performed during the study program;
- Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS), untreated active hepatitis (hepatitis B, defined as hepatitis B virus surface antigen [HBsAg] test positive, HBV-DNA ≥ 500 IU/ mL and abnormal liver function; Hepatitis C, defined as hepatitis C antibody [HCV-AB] positive, HCV-RNA higher than the lower limit of the assay and abnormal liver function) or co-infection with hepatitis B and hepatitis C;
- The patient has an active bacterial or fungal infection (intravenous antibiotics are required at the beginning of the study);
- Prior history of interstitial lung disease, drug-induced interstitial lung disease, radioactive pneumonia requiring steroid treatment, or any evidence of clinically active interstitial lung disease;
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- Arteriovenous thrombosis events, such as cerebrovascular accident (including temporary ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism, occurred within 6 months before enrollment;
- A history of clinically significant cardiovascular disease, including but not limited to; (a) Congestive heart failure (NYHA grade > 2); (b) Unstable angina; (c) had a myocardial infarction within 3 months prior to signing the ICF; (d) Any supraventricular arrhythmia or ventricular arrhythmia requiring treatment or intervention;
- The average QTcF of three electrocardiograms was >470ms
- Have had or had other systemic malignancies within the last 5 years (except cured basal cell carcinoma of the skin and carcinoma in situ and ovarian cancer of the cervix);
- a history of gastrointestinal diseases (such as Crohn's disease, ulcerative colitis, chronic diarrhea, and malabsorption) that affect the absorption of the test drug;
- Use drugs or supplements known to be major contributors to CYP3A4.
- known allergy to any test drug or its excipients;
- Pregnancy, lactation patients, reproductive patients are unwilling to take effective contraceptive measures;
- Prior use of CDK4/6 inhibitors;
- Have a clear past history of neurological or psychiatric disorders, including epilepsy and dementia; Other conditions that the investigator deems inappropriate for inclusion.
About this study
Official title: A Single-center, Single-arm, Phase Ib Clinical Study of the Efficacy and Safety of Dalpiciclib Combined With Third-generation EGFR-TKI in Patients With EGFR Mutation and Meningial Metastasis in Non-small Cell Lung Cancer Progressing Through Third-generation TKI and Platinum-containing Two-drug Chemotherapy
Efficacy and safety of Dalpiciclib combined with third-generation EGFR-TKI in patients with advanced EGFR-mutated non-small cell lung cancer with meningeal metastasis after third-generation TKI and platinum-containing chemotherapy
Read the detailed description
Subjects with advanced NSCLC who developed meningeal progression after previous platinum-based two-drug chemotherapy and third-generation EGFR-TKI treatment were enrolled.
Exploratory analysis: Peripheral blood and/or cerebrospinal fluid samples were retained before medication, 4 weeks after medication, and after progression. Cdk4/6, CDKN2A, CDKN2B, CCND1 (Cyclin D1), CCND2 (Cyclin D2) and CCND3 (Cyclin D2) were detected by NGS D3), CCNE1, RB1 cell cycle pathway changes and subjects without these changes in stratification, namely whether the above cell cycle regulation abnormalities can be used as biomarkers for efficacy prediction and prognosis. And whether there are differences in the expression of the above genes in peripheral blood and cerebrospinal fluid, to explore the relationship between intracranial and extracranial cell cycle regulation abnormalities in the upstream and downstream pathways.
The first stage was the safety introduction period, in which the previous drugs and fixed doses of the third generation EGFR-TKI were continued, and Dalpiciclib was enrolled in the 3+3 mode. After one subject was enrolled, the second subject was enrolled after completing the dose-limiting toxicity (DLT) observation period (3 weeks). If no DLT was found in the 3 subjects, the next dose ramp could be performed. If there was 1 DLT, 3 patients of this dose grade were added to the group. If no DLT was found in any of the 3 cases, the next dose grade was entered. It is planned to enroll 6 to 9 subjects. According to the safety data obtained during the safety observation period, it will be determined whether to add other dose groups for exploration in the first stage after comprehensive analysis and discussion.
- Conditions
- Non-small Cell Lung Cancer Confirmed by Histopathology or Cytology, The TNM (8th) Phase is IV, With EGFR Mutations, Meningeal Progression Occurred After Previous Platinum-containing Two-drug Chemotherapy and Third-generation EGFR-TKI Treatment, Male or Female, The Age of 18 Years Old or More
What is being measured
The primary outcome is the main question the study is designed to answer.
9 of participants
9 of participants
Measured: 1 year
Secondary outcomes (4)
ORR
Overall objective response rate
Measured: 1 year
CNS PFS
CNS Progression-free survival
Measured: 1 year
PFS
Progression-free survival
Measured: 1 year
OS
Overall survival
Measured: through study completion, an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Aug 2022
- Study start1 Sep 2022 (estimated)
- Primary completion1 Jan 2024 (estimated)
- Study completion1 Jul 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-small Cell Lung Cancer Confirmed by Histopathology or CytologyStudies of the same condition, open and under way.
- More trials run by Fujian Cancer HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 9 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fujian Cancer Hospital
- Sponsor type
- Other government
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05497076
- Sponsor's protocol ID
- LM20220606
- Status last verified
- Aug 2022
- First submitted
- 9 Aug 2022
- Last updated
- 11 Aug 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-center, Single-arm, Phase Ib Clinical Study of the Efficacy and Safety of Dalpiciclib Combined With Third-generation EGFR-TKI in Patients With EGFR Mutation and Meningial Metastasis in Non-small Cell Lung Cancer Progressing Through Third-generation TKI and Platinum-containing Two-drug Chemotherapy
- ClinicalTrials.gov ID
- NCT05497076
- Acronym / sponsor ID
- LM20220606
- Conditions
- Non-small Cell Lung Cancer Confirmed by Histopathology or Cytology, The TNM (8th) Phase is IV, With EGFR Mutations, Meningeal Progression Occurred After Previous Platinum-containing Two-drug Chemotherapy and Third-generation EGFR-TKI Treatment, Male or Female, The Age of 18 Years Old or More
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 9 participants (estimated)
- Lead sponsor
- Fujian Cancer HospitalOther government
- Study start
- 1 Sep 2022 (estimated)
- Primary completion
- 1 Jan 2024 (estimated)
- Study completion
- 1 Jul 2024 (estimated)
- First posted
- 11 Aug 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Efficacy and safety of Dalpiciclib combined with third-generation EGFR-TKI in patients with advanced EGFR-mutated non-small cell lung cancer with meningeal metastasis after third-generation TKI and platinum-containing chemotherapy
Detailed description
Subjects with advanced NSCLC who developed meningeal progression after previous platinum-based two-drug chemotherapy and third-generation EGFR-TKI treatment were enrolled.
Exploratory analysis: Peripheral blood and/or cerebrospinal fluid samples were retained before medication, 4 weeks after medication, and after progression. Cdk4/6, CDKN2A, CDKN2B, CCND1 (Cyclin D1), CCND2 (Cyclin D2) and CCND3 (Cyclin D2) were detected by NGS D3), CCNE1, RB1 cell cycle pathway changes and subjects without these changes in stratification, namely whether the above cell cycle regulation abnormalities can be used as biomarkers for efficacy prediction and prognosis. And whether there are differences in the expression of the above genes in peripheral blood and cerebrospinal fluid, to explore the relationship between intracranial and extracranial cell cycle regulation abnormalities in the upstream and downstream pathways.
The first stage was the safety introduction period, in which the previous drugs and fixed doses of the third generation EGFR-TKI were continued, and Dalpiciclib was enrolled in the 3+3 mode. After one subject was enrolled, the second subject was enrolled after completing the dose-limiting toxicity (DLT) observation period (3 weeks). If no DLT was found in the 3 subjects, the next dose ramp could be performed. If there was 1 DLT, 3 patients of this dose grade were added to the group. If no DLT was found in any of the 3 cases, the next dose grade was entered. It is planned to enroll 6 to 9 subjects. According to the safety data obtained during the safety observation period, it will be determined whether to add other dose groups for exploration in the first stage after comprehensive analysis and discussion.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Non-small cell lung cancer diagnosed by histopathology or cytology, TNM (8th) stage IV, accompanied by EGFR mutation, meningeal progression after previous platinum-containing two-drug chemotherapy and third-generation EGFR-TKI treatment, male and female, age ≥18 years, ECOG PS score 0-2
Key inclusion criteria (10 listed)
- Age ≥18 when signing informed consent, both male and female;
- Advanced or metastatic NSCLC confirmed by histology or cytology is stage IV according to THE TNM stage of lung cancer, IASLC 2015 Eighth Edition;
- EgFR-sensitive mutations (exon 19 deletion, exon 21 L858R or L861Q mutation, exon 18 G719X mutation, etc.) exist. Meningeal progression follows platinum-containing chemotherapy in combination with/without antivascular and/or in combination with/without immunotherapy, and 3 generations of EGFR-TKI (which can be 1+3, 2+3 or directly after 3 generations of targeted therapy). Patients with BMS can be treated with brain radiotherapy. Cerebrospinal fluid and peripheral blood were collected for EXPLORATORY NGS testing. Subjects identified with cdK4/6, CDKN2A, CDKN2B, CCND1 (Cyclin D1), CCND2 (Cyclin D2), CCND3 (Cyclin D3), CCNE1 and RB1 cell cycle pathway changes by genetic testing were stratified for analysis;
- ECOG PS score: 0-2;
- Normal function of major organs, that is, meeting the following criteria: a) blood routine examination (no blood transfusion within 14 days, no hematopoietic stimulation drugs correction) : Hemoglobin (Hb) ≥90g/L; Absolute neutrophil count (ANC) ≥1.5×109/L; Platelet (PLT) ≥100×109/L; White blood cell count (WBC) ≥3.0×109/L; B) Biochemical examination: ALT and AST ≤2.5× upper limit of normal value (ULN); Serum total bilirubin (TBIL) ≤1.5×ULN; Serum creatinine (Cr) ≤1.5×ULN or creatinine clearance ≥50ml/min; If liver metastasis was present, total bilirubin ≤3×ULN, ALT and AST≤5×ULN; C) Coagulation function: activated partial thrombin time (APTT), international standardized ratio (INR), prothrombin time (PT) ≤1.5×ULN; D) Doppler ultrasound assessment: left ventricular ejection fraction (LVEF)≥50%;
Key exclusion criteria (16 listed)
- Second-line or above chemotherapy or other anti-tumor drugs;
- Cerebral edema requiring hormone dehydration treatment;
- Major surgery performed within 4 weeks prior to the start of the study treatment or planned to be performed during the study program;
- Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS), untreated active hepatitis (hepatitis B, defined as hepatitis B virus surface antigen [HBsAg] test positive, HBV-DNA ≥ 500 IU/ mL and abnormal liver function; Hepatitis C, defined as hepatitis C antibody [HCV-AB] positive, HCV-RNA higher than the lower limit of the assay and abnormal liver function) or co-infection with hepatitis B and hepatitis C;
- The patient has an active bacterial or fungal infection (intravenous antibiotics are required at the beginning of the study);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
9 of participants
Time frame: 1 year
9 of participants
4 secondary outcomes
ORR
Time frame: 1 year
CNS PFS
Time frame: 1 year
PFS
Time frame: 1 year
OS
Time frame: through study completion, an average of 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Aug 2022.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
An observational study of Non-small Cell Lung Cancer Confirmed by Histopathology or Cytology and The TNM (8th) Phase is IV, run by Fujian Cancer Hospital.
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 16 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 11 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
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?
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?
9 of participants (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 11 Aug 2022.