Olanzapine or Dexamethasone, With 5-HT3 RA and NK-1 RA, to Prevent CINV

NCT ID: NCT04437017

Last Updated: 2022-07-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 557 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-02-03
• Study Completion Date: 2022-07-01

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.

Conditions

Chemotherapy-induced Nausea and Vomiting

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Olanzapine+NK-1 RA+5-HT3 RA

Using one of the 5-HT3 receptor antagonists (a. Palonosetron: 0.25 mg d1 intravenous; b. Granisetron: 1 mg d1 intravenously, or 2 mg d1 orally; c. Ondansetron: 8-16 mg d1 intravenous or oral. the specific agent is chosen by the primary clinician, and is only delivered on the first day) within 30 minutes before cisplatin. Using one of the NK-1 receptor antagonists(a. Aprepitant: 125 mg orally, d1, 80 mg orally, d2-3; b. Fosaprepitant: 150 mg intravenously, d1) within 1 hour before cisplatin. On day 1-4, Olanzapine (5mg) is delivered orally after dinner.

Group Type: EXPERIMENTAL

Olanzapine+NK-1 RA+5-HT3 RA

Intervention Type: DRUG

On day 1-4, Olanzapine (5mg) is delivered orally after dinner.

Dexamethasone+NK-1 RA+5-HT3 RA

Using one of the 5-HT3 receptor antagonists (a. Palonosetron: 0.25 mg d1 intravenous; b. Granisetron: 1 mg d1 intravenously, or 2 mg d1 orally; c. Ondansetron: 8-16 mg d1 intravenous or oral. the specific agent is chosen by the primary clinician, and is only delivered on the first day) within 30 minutes before cisplatin. Using one of the NK-1 receptor antagonists (a. Aprepitant: 125 mg orally, d1, 80 mg orally, d2-3; b. Fosaprepitant: 150 mg intravenously, d1) within 1 hour before cisplatin. On first day, dexamethasone (12 mg) is given orally/intravenously within 30 minutes before cisplatin administered, and on day 2-4, the given dose of dexamethasone is 8 mg.

Group Type: ACTIVE_COMPARATOR

Dexamethasone+NK-1 RA+5-HT3 RA

Intervention Type: DRUG

On first day, dexamethasone (12 mg) is given orally/intravenously within 30 minutes before cisplatin administrated, and on day 2-4, the given dose of dexamethasone is 8 mg.

Interventions

Olanzapine+NK-1 RA+5-HT3 RA

On day 1-4, Olanzapine (5mg) is delivered orally after dinner.

Intervention Type: DRUG

Dexamethasone+NK-1 RA+5-HT3 RA

On first day, dexamethasone (12 mg) is given orally/intravenously within 30 minutes before cisplatin administrated, and on day 2-4, the given dose of dexamethasone is 8 mg.

Intervention Type: DRUG

Other Intervention Names

Acidocont; Deronil; Dexacortal; Desameton; Fluprednisolone; (11β，16α）-9-Fluoro-11,17,21-trihydroxy-16-methylpregna-1,4-diene-3,20-dione

Eligibility Criteria

Inclusion 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

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fifth Affiliated Hospital, Sun Yat-Sen University

OTHER

Sponsor Role: lead

Responsible Party

Zhigang Liu

Vice Director

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Zhigang Liu, M.D.

Role: STUDY_DIRECTOR

Fifth Affilliated Hospital of Sun Yat-sen University

Zhigang Liu, M.D.

Role: PRINCIPAL_INVESTIGATOR

Fifth Affilliated Hospital of Sun Yat-sen University

Locations

Fifth Affilliated Hospital of Sun Yat-sen University

Zhuhai, Guangdong, China

Countries

China

Other Identifiers

No.ZDWY[2020]LunziNo.(K01-1)

Identifier Type: -

Identifier Source: org_study_id