Olanzapine and 5-HT3 With or Without Dexamethasone to Prevent CINV

Chemotherapy-induced Nausea and Vomiting Clinical Trial

Official title:

Olanzapine and 5-HT3 With or Without Dexamethasone to Prevent Nausea and Vomiting Induced by Chemotherapy：:A Non-inferiority, Prospective, Multi-Centered, Randomized, Controlled, Phase III Clinical Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05805800
• Other study ID #: 2023-157
• Status: Recruiting
• Phase: Phase 3
• Start date: March 15, 2023
• Est. completion date: March 15, 2025

Study information

• Verified date: November 2023
• Source: West China Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Nausea and vomiting caused by chemotherapy are considered by patients as the main side effects of cancer treatment, which affect the quality of treatment and life.At present, NCCN guidelines have recommended three or four drug regimens for highly emetic chemotherapy (HEC) to prevent vomiting, all containing dexamethasone.However, its side effects such as moderate to severe insomnia, hyperglycemia, dyspepsia, upper abdominal discomfort, irritability, increased appetite, weight gain and acne are gathering increasing concerns.For certain patients, the use of dexamethasone should be avoided.Analysis shows that olanzapine can replace the effect of dexamethasone.Hence, the investigators initiated this prospective, multi-center, phase III study to validate the dexamethasone-free protocol: removing dexamethasone from a three drug regimen containing olanzapine, dexamethasone, and 5-HT3RA.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 238
• Est. completion date: March 15, 2025
• Est. primary completion date: March 15, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Patients 18 years of age or older with malignant disease;

2. Life expectancy = 3 months;

3. Scheduled to receive highly emetogenic chemotherapy;

4. Had a European Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

Exclusion Criteria:

1. There are contraindications to chemotherapy(Absolute number of neutrophils = 1,500/uL, hemoglobin = 90g/L, platelet count = 10000/uL, serum creatinine level = 2.0mg/dl (177 µmol/L), ALT and AST = 2.5 times the upper normal limit, bilirubin = 1.5 times the upper normal limit);

2. History of central nervous system disease (e.g., brain metastases or a seizure disorder);

3. Severe cognitive impairment;

4. Treatment with another antipsychotic agent such as risperidone, quetiapine, clozapine, a phenothiazine, or a butyrophenone within 30 days before enrollment or plans for such treatment during the study period;

5. Concurrent use of pharyngeal or abdominal radiotherapy;

6. Concurrent use of quinolone antibiotics;

7. Concurrent use of Amifostine;

8. Chronic alcoholism;

9. Known hypersensitivity to olanzapine;

10. Know arrhythmia, uncontrolled congestive heart failure or acute myocardial infarction within 6 months;

11. Known uncontrolled diabetes mellitus;

12. Vomiting or retching 24 hours before chemotherapy;

13. Use of anti-emesis drugs 48 hours before chemotherapy;

14. Patients who require medication with dexamethasone for pretreatment.

Related Conditions & MeSH terms

• Chemotherapy-induced Nausea and Vomiting
• Nausea
• Vomiting

Intervention

Drug:
• 5HT3RA+Olanzapine
Using one of the 5-HT3 receptor antagonists within 30 minutes before cisplatin/adriamycin/cyclophosphamide. On day 1-4, Olanzapine is delivered orally after dinner.
• 5HT3RA+Olanzapine+Dexamethasone
Using one of the 5-HT3 receptor antagonists within 30 minutes before cisplatin/adriamycin/cyclophosphamide. On day 1-4, Olanzapine is delivered orally after dinner. On first day, dexamethasone is given orally within 30 minutes before cisplatin/adriamycin/cyclophosphamide administered. Other Names: Acidocont; Deronil; Dexacortal; Desameton; Fluprednisolone; (11ß,16a-9-Fluoro-11,17,21-trihydroxy-16-methylpregna-1,4-diene-3,20-dione

Locations

Country	Name	City	State
China	West China Hospital, Sichuan University	Chengdu	Sichuan

Sponsors (1)

Lead Sponsor	Collaborator
Xingchen Peng

Country where clinical trial is conducted

China, 

References & Publications (6)

Chelkeba L, Gidey K, Mamo A, Yohannes B, Matso T, Melaku T. Olanzapine for chemotherapy-induced nausea and vomiting: systematic review and meta-analysis. Pharm Pract (Granada). 2017 Jan-Mar;15(1):877. doi: 10.18549/PharmPract.2017.01.877. Epub 2017 Mar 15 — View Citation

Hu Z, Cheng Y, Zhang H, Zhou C, Han B, Zhang Y, Huang C, Chang J, Song X, Liang J, Liang H, Bai C, Yu S, Chen J, Wang J, Pan H, Chitkara DK, Hille DA, Zhang L. Aprepitant triple therapy for the prevention of chemotherapy-induced nausea and vomiting follow — View Citation

Navari RM, Qin R, Ruddy KJ, Liu H, Powell SF, Bajaj M, Dietrich L, Biggs D, Lafky JM, Loprinzi CL. Olanzapine for the Prevention of Chemotherapy-Induced Nausea and Vomiting. N Engl J Med. 2016 Jul 14;375(2):134-42. doi: 10.1056/NEJMoa1515725. — View Citation

Ng TL, Hutton B, Clemons M. Chemotherapy-Induced Nausea and Vomiting: Time for More Emphasis on Nausea? Oncologist. 2015 Jun;20(6):576-83. doi: 10.1634/theoncologist.2014-0438. Epub 2015 May 6. — View Citation

Tan L, Liu J, Liu X, Chen J, Yan Z, Yang H, Zhang D. Clinical research of Olanzapine for prevention of chemotherapy-induced nausea and vomiting. J Exp Clin Cancer Res. 2009 Sep 23;28(1):131. doi: 10.1186/1756-9966-28-131. — View Citation

Yang LQ, Sun XC, Qin SK, Cheng Y, Shi JH, Chen ZD, Wang QM, Zhang HL, Hu B, Liu B, Zhang QY, Wu Q, Wang D, Shu YQ, Dong J, Han BH, Wang KM, Dang CX, Li JL, Wang HB, Li BL, Lu JG, Zhang ZH, Chen YX. Efficacy and safety of fosaprepitant in the prevention of — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	0-120h Complete Remission Rate	The ratio of patients who have no vomiting and apply no anti-nausea drugs during the whole observation period.	24 hours ,48 hours, 72 hours, 96 hours, 120 hours after chemotherapy
Secondary	25-120 hours Complete Remission Rate	The ratio of patients who have no vomiting and apply no anti-nausea drugs during the 25-120 hours observation period.	24 hours ,48 hours, 72 hours, 96 hours, 120 hours after chemotherapy
Secondary	0-120h No Nausea Rate	The ratio of patients who have no nausea during the whole observation period.	24 hours, 48 hours, 72 hours, 96 hours, 120 hours after chemotherapy