Trial Title:
Olanzapine Impact on First-line Immunotherapy for Advanced EGFR-negative NSCLC
NCT ID:
NCT06554613
Condition:
Non-Small Cell Lung Cancer
Conditions: Official terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Nivolumab
Olanzapine
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Olanzapine
Description:
Olanzapine 5mg qd (once daily), q3w(every 3 weeks), oral therapy，Administered
continuously for 6-8 weeks.
Arm group label:
Olanzapine in Combination with Immune Checkpoint Inhibitors Treatment Group
Other name:
Zyprexa
Intervention type:
Drug
Intervention name:
Nivolumab
Description:
Nivolumab，Infused intravenously once every 3 weeks at a dose of 2mg/kg, with a continuous
21-day treatment period constituting one treatment cycle.
Arm group label:
Group Without Olanzapine
Arm group label:
Olanzapine in Combination with Immune Checkpoint Inhibitors Treatment Group
Other name:
Opdivo
Summary:
Clinical Trial
The objective of this clinical trial is to determine whether antidepressant medications,
such as olanzapine, in combination with immune checkpoint inhibitors are more effective
than the use of immune checkpoint inhibitors alone. The main questions it aims to answer
are:
Is the combination therapy of antidepressant medication with immune checkpoint inhibitors
more efficacious than the therapy with immune checkpoint inhibitors alone? What medical
issues might participants encounter when treated with the combination of antidepressant
medication and immune checkpoint inhibitors?
Participants will:
Take olanzapine in combination with immune checkpoint inhibitors or immune checkpoint
inhibitors alone for 2 months.
Visit the clinic for check-ups and tests every two weeks, and have follow-up visits every
six weeks after the treatment ends.
Keep a record of their symptoms and disease progression.
Detailed description:
An Open-label, Two-arm, Multicenter, Phase II Randomized Controlled Study on the Impact
of Olanzapine on the Efficacy of First-line Immunotherapy in Patients with Advanced EGFR
Mutation-negative Non-small Cell Lung Cancer (NSCLC).
Primary Research Objective:
To evaluate the objective response rate (ORR) in patients with advanced EGFR
mutation-negative NSCLC treated with first-line PD-1/PD-L1 inhibitors combined with
olanzapine.
Secondary Research Objectives:
To evaluate the interval of progression-free survival (iPFS) in patients with advanced
EGFR mutation-negative NSCLC treated with first-line PD-1/PD-L1 inhibitors combined with
olanzapine.
To evaluate other antitumor efficacy indicators in patients with advanced EGFR
mutation-negative NSCLC treated with first-line PD-1/PD-L1 inhibitors combined with
olanzapine: progression-free survival (PFS), duration of response (DoR), and disease
control rate (DCR).
To assess the safety (Safety) and the improvement of quality of life (QoL) in patients
with advanced EGFR mutation-negative NSCLC treated with first-line PD-1/PD-L1 inhibitors
combined with olanzapine.
To explore the impact of antipsychotic medication on the immune response to first-line
immunotherapy in advanced NSCLC.
Study Design:
This study is an open-label, two-arm, multicenter, phase II randomized controlled study
designed to evaluate and observe the impact of olanzapine on the efficacy of first-line
immunotherapy in patients with advanced EGFR mutation-negative NSCLC. Eligible
participants who meet all inclusion criteria and do not meet any exclusion criteria will
receive first-line treatment with PD-1/PD-L1 monoclonal antibodies alone or in
combination with chemotherapy (according to the instructions for use).
Study Subjects:
Ages 18 years and above (including 18) and up to 75 years (including 75); histologically
or cytologically confirmed EGFR mutation-negative NSCLC; intended to receive first-line
treatment with PD-1/PD-L1 inhibitors alone or in combination with chemotherapy.
Inclusion Criteria:
Participants voluntarily join this study and sign an informed consent form, with good
compliance and cooperation with follow-up.
Age is 18 years and above (including 18) and up to 75 years (including 75). ECOG score:
0-2 points. Expected survival is no less than 3 months. Staged as Stage IV according to
the TNM system. Confirmed to have NSCLC with EGFR mutation-negative by histology or
cytology. Has not received systemic antitumor treatment, and is intended to receive
first-line treatment with PD-1/PD-L1 inhibitors alone or in combination with
chemotherapy.
Normal major organ function, that is, meeting the following criteria: (1) Hematological
examination criteria must be met: Hb≥90 g/L; ANC≥1.5×10^9/L; PLT≥80×10^9/L. (2)
Biochemical examination must meet the following criteria: TBIL<1.5ULN; ALT and
AST<2.5ULN; serum Cr≤1.25ULN or endogenous creatinine clearance > 45 ml/min
(Cockcroft-Gault formula).
Women of childbearing age must have taken reliable contraceptive measures and have
undergone a pregnancy test (serum or urine) within 7 days before enrollment, with a
negative result, and are willing to use appropriate methods of contraception during the
trial period and for 8 weeks after the last administration of the trial medication. For
men, they must agree to use appropriate methods of contraception during the trial period
and for 8 weeks after the last administration of the trial medication or have undergone
surgical sterilization.
Data Analysis/Statistical Methods:
Common Analysis This study will summarize the data using corresponding descriptive
statistics according to the type of data, that is, for quantitative data, mean (Mean),
standard deviation (SD), median (Median), minimum value (Minimum), and maximum value
(Maximum) will be used, and for count data and grade data, frequency and percentage will
be used, and time-event data will be estimated by the Kaplan-Meier method for the median
time and the overall 95% confidence interval.
Efficacy Analysis The primary efficacy endpoint, the objective response rate (ORR) based
on the investigator's assessment, will be compared between groups using the Fisher's
exact probability test and the two-sided 95% confidence interval will be listed.
The secondary efficacy indicators, including the interval of progression-free survival
(iPFS), progression-free survival (PFS), duration of response (DoR), and disease control
rate (DCR), will be estimated using the Kaplan-Meier method for the median time and the
median event and the two-sided 95% confidence interval will be listed, and the hazard
ratio and its 95% confidence interval will be estimated. The disease control rate (DCR =
CR + PR + SD) will be compared between groups using Fisher's exact probability test and
the two-sided 95% confidence interval will be listed. Quality of life score statistical
tests will use ANOVA or two-sided t-tests, and a P-value less than or equal to 0.05 will
be considered statistically significant. Comparisons of changes before and after within
groups will be made using paired t-tests.
Safety Analysis Safety analysis will mainly summarize descriptive statistics. Statistics
will be summarized for adverse events (AEs) and treatment-emergent adverse events
(TEAEs), serious adverse events (SAEs), and laboratory data, vital signs, etc. At the
same time, statistical summaries will be made for the exposure to the study drug
(including treatment cycles, total dose received, and dose intensity). The above data
will be analyzed and summarized according to the current clinical trial reporting
standards. Including: summary of adverse events (all causes and related to treatment);
incidence and severity of adverse events (all causes and related to treatment); analysis
of adverse events related to the drug; analysis of the outcome of adverse events;
analysis of serious adverse events.
Sample Size Estimation:
This study is an open-label, two-arm, multicenter, phase II randomized controlled study.
The primary research objective is to evaluate the objective response rate (ORR) in
patients with advanced EGFR mutation-negative NSCLC treated with first-line PD-1/PD-L1
inhibitors combined with olanzapine. The study endpoint is the objective response rate
(ORR) of the patients. Referring to historical literature, the ORR of first-line
chemotherapy combined with immunotherapy in advanced NSCLC patients is about 50%, and it
is expected that the combination with olanzapine can increase the ORR by 15%. After the
first subject is enrolled, the longest observation period is 24 months, with α being
two-sided 0.05, and the power being 90%, the study plans to enroll 156 subjects, with 78
in the experimental group and 78 in the control group, calculated with a 10% loss to
follow-up rate.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Participants voluntarily enroll in this study and sign an informed consent form,
with good compliance and cooperation with follow-up.
2. Age is over 18 years old (including 18 years old) and under 75 years old (including
75 years old).
3. ECOG score: 0-2 points.
4. Expected survival is no less than 3 months.
5. Staged as Stage IV according to the TNM system.
6. Histologically or cytologically confirmed EGFR mutation-negative non-small cell lung
cancer.
7. Has not received systemic antitumor treatment, and is intended to receive
monotherapy or combined chemotherapy with a PD-1/PD-L1 inhibitor as first-line
treatment.
8. Normal major organ function, that is, meeting the following criteria: (1)
Hematological examination criteria must be met: Hb≥90 g/L; ANC≥1.5×10^9/L;
PLT≥80×10^9/L. (2) Biochemical examination must meet the following criteria:
TBIL<1.5×ULN; ALT and AST<2.5×ULN; serum Cr≤1.25×ULN or endogenous creatinine
clearance > 45 ml/min (Cockcroft-Gault formula).
9. Women of childbearing age must have taken reliable contraceptive measures and have
undergone a pregnancy test (serum or urine) within 7 days before enrollment, with a
negative result, and are willing to use appropriate methods of contraception during
the trial period and for 8 weeks after the last administration of the trial
medication. For men, they must agree to use appropriate methods of contraception
during the trial period and for 8 weeks after the last administration of the trial
medication or have undergone surgical sterilization.
Exclusion Criteria:
1. Have received any of the following treatments:
1. Previously used any EGFR tyrosine kinase inhibitors;
2. Previously received any chemotherapy for lung cancer;
3. Previously received any radiotherapy for lung cancer (except palliative
radiotherapy for bone metastases);
4. Within 4 weeks prior to the first administration of the study drug, the subject
had undergone major surgery;
5. Within 7 days prior to the first administration of the study drug, used strong
inhibitors or inducers of CYP3A4.
2. Subjects with concurrent other malignant tumors, except for basal cell carcinoma of
the skin and in situ cancer.
3. Subjects with uncontrollable malignant pleural effusion and pericardial effusion.
4. Subjects allergic to contrast agents for CT and MRI or any subjects who cannot
tolerate MRI examination.
5. As judged by the investigator, any serious or poorly controlled systemic diseases,
such as uncontrolled hypertension, active bleeding diathesis, or active infection.
6. Clinically severe gastrointestinal functional abnormalities that may affect the
intake, transport, or absorption of the drug, such as the inability to take oral
medication, uncontrollable nausea or vomiting, history of extensive gastrointestinal
resection, unresolved recurrent diarrhea, atrophic gastritis, gastric diseases
requiring long-term use of proton pump inhibitors, Crohn's disease, ulcerative
colitis, etc.
7. Hepatic encephalopathy, hepatorenal syndrome, or liver cirrhosis.
8. Meet any of the following cardiac examination results:
1. The average of the corrected QT interval (QTcF) obtained from three ECG
examinations at rest is > 470 msec;
2. Resting ECG suggests conduction or ECG morphological abnormalities (such as
complete left bundle branch block, third-degree atrioventricular block,
second-degree atrioventricular block, and PR interval > 250 msec, etc.);
3. There are any factors that increase the risk of QTc prolongation or arrhythmic
events, such as heart failure, hypokalemia, congenital long QT syndrome, family
history of long QT syndrome, or any concurrent medication of unexplained sudden
death in direct relatives under the age of 40 or prolonged QT interval;
4. Left ventricular ejection fraction (LVEF) < 50%.
9. Insufficient bone marrow reserve or organ function, reaching any of the following
laboratory limits:
1. Absolute neutrophil count <1.5×10^9/L;
2. Platelet count <100×10^9/L;
3. Hemoglobin <90 g/L (<9 g/dL);
4. If there is no definite liver metastasis, alanine aminotransferase > 3 times
the upper limit of normal (ULN); if there is liver metastasis, alanine
aminotransferase > 5×ULN;
5. If there is no definite liver metastasis, aspartate aminotransferase >3×ULN; if
there is liver metastasis, aspartate aminotransferase > 5×ULN;
6. If there is no definite liver metastasis, total bilirubin > 1.5×ULN; or with
Gilbert's syndrome (unconjugated hyperbilirubinemia) or liver metastasis, total
bilirubin > 3×ULN;
7. Creatinine > 1.5×ULN and creatinine clearance <50 mL/min (calculated by the
Cockcroft-Gault formula); creatinine clearance is only required if creatinine >
1.5×ULN;
8. Serum albumin (ALB) <28 g/L.
10. Active fungal, bacterial, and/or viral infections requiring systemic treatment.
11. Female subjects who are pregnant, breastfeeding, or planning to become pregnant
during the study period.
12. History of interstitial lung disease, drug-induced interstitial lung disease,
history of radiation pneumonitis requiring steroid treatment, or any evidence of
clinically active interstitial lung disease.
13. Subjects who, in the judgment of the investigator, may have poor compliance with the
procedures and requirements of the study, such as subjects with a clear history of
neurological or mental disorders, currently suffering from mental disorders, etc.
14. Subjects whom the investigator judges to have any condition that endangers the
safety of the subject or interferes with the evaluation of the study.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Start date:
December 1, 2024
Completion date:
May 31, 2028
Lead sponsor:
Agency:
Second Affiliated Hospital of Nanchang University
Agency class:
Other
Source:
Second Affiliated Hospital of Nanchang University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06554613
