Olanzapine Impact on First-line Immunotherapy for Advanced EGFR-negative NSCLC

NCT06554613 | Recruiting Phase 2 DMC

• 1 other identifier: IIT-2024-6804
• Study Type: interventional
• Target: 156
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• The Overall Survival（OS）

  The Overall Survival（OS），From the time of a patient's diagnosis or the commencement of treatment, to the time of the patient's death.

  24 months

Study Arms (2)

Olanzapine in Combination with Immune Checkpoint Inhibitors Treatment Group

EXPERIMENTAL

Receiving first-line treatment with a PD-1/PD-L1 inhibitor as a single agent or in combination with chemotherapy (according to the instructions manual)，Medication is administered on the first day of each cycle, with one cycle every 3 weeks. A continuous 21-day treatment constitutes one treatment cycle.Then receive olanzapine orally at a dose of 5mg once daily (qd), with continuous administration for 6-8 weeks.

Drug: Olanzapine; Drug: Nivolumab

Group Without Olanzapine

ACTIVE COMPARATOR

Receiving first-line treatment with a PD-1/PD-L1 inhibitor as a single agent or in combination with chemotherapy (according to the instructions manual)，Medication is administered on the first day of each cycle, with one cycle every 3 weeks. A continuous 21-day treatment constitutes one treatment cycle..

Drug: Nivolumab

Interventions

Olanzapine DRUG

Olanzapine 5mg qd (once daily), q3w(every 3 weeks), oral therapy，Administered continuously for 6-8 weeks.

Also known as: Zyprexa

Olanzapine in Combination with Immune Checkpoint Inhibitors Treatment Group

Nivolumab DRUG

Nivolumab，Infused intravenously once every 3 weeks at a dose of 2mg/kg, with a continuous 21-day treatment period constituting one treatment cycle.

Also known as: Opdivo

Group Without Olanzapine; Olanzapine in Combination with Immune Checkpoint Inhibitors Treatment Group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants voluntarily enroll in this study and sign an informed consent form, with good compliance and cooperation with follow-up.
• Age is over 18 years old (including 18 years old) and under 75 years old (including 75 years old).
• ECOG score: 0-2 points.
• Expected survival is no less than 3 months.
• Staged as Stage IV according to the TNM system.
• Histologically or cytologically confirmed EGFR mutation-negative non-small cell lung cancer.
• 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.
• 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).
• 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.

You may not qualify if:

• Have received any of the following treatments:
• Previously used any EGFR tyrosine kinase inhibitors;
• Previously received any chemotherapy for lung cancer;
• Previously received any radiotherapy for lung cancer (except palliative radiotherapy for bone metastases);
• Within 4 weeks prior to the first administration of the study drug, the subject had undergone major surgery;
• Within 7 days prior to the first administration of the study drug, used strong inhibitors or inducers of CYP3A4.
• Subjects with concurrent other malignant tumors, except for basal cell carcinoma of the skin and in situ cancer.
• Subjects with uncontrollable malignant pleural effusion and pericardial effusion.
• Subjects allergic to contrast agents for CT and MRI or any subjects who cannot tolerate MRI examination.
• As judged by the investigator, any serious or poorly controlled systemic diseases, such as uncontrolled hypertension, active bleeding diathesis, or active infection.
• 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.
• Hepatic encephalopathy, hepatorenal syndrome, or liver cirrhosis.
• Meet any of the following cardiac examination results:
• The average of the corrected QT interval (QTcF) obtained from three ECG examinations at rest is \> 470 msec;
• 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.);

Sponsors & Collaborators

• Second Affiliated Hospital of Nanchang University: lead

Study Sites (1)

The Second Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, 330006, China

RECRUITING

Related Publications (2)

• Wang M, Herbst RS, Boshoff C. Toward personalized treatment approaches for non-small-cell lung cancer. Nat Med. 2021 Aug;27(8):1345-1356. doi: 10.1038/s41591-021-01450-2. Epub 2021 Aug 12.

  PMID: 34385702 BACKGROUND

• Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249. doi: 10.3322/caac.21660. Epub 2021 Feb 4.

  PMID: 33538338 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Olanzapine; Nivolumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Lin Chuyang, Director

  Nanchang University

  STUDY DIRECTOR

Central Study Contacts

Huang Long, Director

CONTACT

+86 13699549060; huanglongdoctor@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 2, 2024
• First Posted: August 15, 2024
• Study Start: July 2, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): May 31, 2027
• Last Updated: May 5, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)