Clinical trial NCT04437017: Olanzapine or Dexamethasone, With 5-HT3 RA and NK-1 RA, to Prevent CINV
Official title: Olanzapine or Dexamethasone, With 5-HT3 RA and NK-1 RA, to Prevent Nausea and Vomiting Induced by Cisplatin-Based Doublet 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
Keywords: nausea
vomiting
antiemesis
Lead sponsor: Fifth Affiliated Hospital, Sun Yat-Sen University
Sponsor class: OTHER
First posted: 2020-06-18
Enrollment: 557
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Chemotherapy-induced nausea and vomiting is a common side effect of cancer treatments, and dexamethasone offers a clear advantage over placebo for protection against chemotherapy-induced emesis in both acute and delayed phases. 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. Several clinical trials have shown that olanzapine plays an important role in treating delayed, refractory, breakthrough nausea and vomiting. Its side effects mainly include sedation and weight gaining. At present, the NCCN guidelines have recommended olanzapine-containing three-drug regimen for Highly Emetogenic Chemotherapy (HEC) and moderate emetic chemotherapy (MEC) to prevent vomiting, but its data in the Chinese population is limited. Hence, we initiated this prospective, multi-center, phase III study to validate the dexamethasone-free protocol: applying olanzapine to prevent CINV instead of dexamethasone.


Eligibility criteria: Inclusion Criteria (Patients are eligible to be included in the study only if they meet all of the following criteria):

1. Cancer patients, age ≥ 18 years and ≤75 years, ECOG score 0-2 points, receiving cisplatin-containing doublet chemotherapy such as cisplatin + gemcitabine / albumin paclitaxel / etoposide /fluorouracil / irinotecan / temozolomide as first line treatment;
2. Life expectancy ≥ 3 months;
3. Leucocytes≥3,000/uL;
4. AST≤2.5 × upper limit of normal;
5. Bilirubin ≤1.5 × upper limit of normal;
6. Serum creatinine ≤ 1.5 × upper limit of normal.

Exclusion Criteria (Patients will be excluded if any of the following criteria is met):

1. History of CNS disease, such as brain metastases or epilepsy;
2. Use of other antipsychotic drugs (such as risperidone, quetiapine, clozapine, phenothiazine, or butyrophenone, or such treatment is under scheduling during the study) within 30 days before enrollment; long-term use of phenothiazine as an antipsychotic agent;
3. Concurrent use of pharyngeal or abdominal radiotherapy;
4. Concurrent use of quinolone antibiotics;
5. Chronic alcoholism;
6. Known hypersensitivity to olanzapine;
7. Know arrhythmia, uncontrolled congestive heart failure or acute myocardial infarction within 6 months;
8. Known uncontrolled diabetes mellitus;
9. Vomiting or retching 24 hours before chemotherapy;
10. Use of anti-emesis drugs 48 hours before chemotherapy;
11. Concurrent use of amifostine;
12. Concurrent use of corticosteroids and the only anti-allergic choice is corticosteroids

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: Zhuhai
country: China
facility: Fifth Affilliated Hospital of Sun Yat-sen University
state: Guangdong
Study officials:
affiliation: Fifth Affilliated Hospital of Sun Yat-sen University
name: Zhigang Liu, M.D.
role: STUDY_DIRECTOR
affiliation: Fifth Affilliated Hospital of Sun Yat-sen University
name: Zhigang Liu, M.D.
role: PRINCIPAL_INVESTIGATOR
References: