Clinical trial NCT05805800: Olanzapine and 5-HT3 With or Without Dexamethasone to Prevent CINV
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chemotherapy-induced Nausea and Vomiting
Lead sponsor: West China Hospital
Sponsor class: OTHER
First posted: 2023-04-10
Enrollment: 275
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: 0-120h Complete Remission Rate
timeFrame: 24 hours ,48 hours, 72 hours, 96 hours, 120 hours after chemotherapy
Secondary outcomes:
measure: 25-120 hours Complete Remission Rate
timeFrame: 24 hours ,48 hours, 72 hours, 96 hours, 120 hours after chemotherapy
measure: 0-120h No Nausea Rate
timeFrame: 24 hours, 48 hours, 72 hours, 96 hours, 120 hours after chemotherapy
Other outcomes:
Locations:
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
state: Sichuan
Study officials:
References:
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.
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 nausea and vomiting following highly emetogenic chemotherapy in Chinese people: A randomized, double-blind, phase III study. Eur J Cancer Care (Engl). 2017 Nov;26(6):e12668. doi: 10.1111/ecc.12668. Epub 2017 Apr 10.
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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.
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.
citation: 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.