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

July 26, 2022 updated by: Zhigang Liu, Fifth Affiliated Hospital, Sun Yat-Sen University

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

557

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Guangdong
      • Zhuhai, Guangdong, China
        • Fifth Affilliated Hospital of Sun Yat-sen University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Drug: Olanzapine+NK-1 RA+5-HT3 RA
On day 1-4, Olanzapine (5mg) is delivered orally after dinner.
Active Comparator: 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.
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.
Other Names:
  • Deronil
  • Desameton
  • Dexacortal
  • Acidocont
  • Fluprednisolone
  • (11β，16α）-9-Fluoro-11,17,21-trihydroxy-16-methylpregna-1,4-diene-3,20-dione

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
0-120h Complete Remission Rate
Time Frame: 24 hours ,48 hours, 72 hours, 96 hours, 120 hours after chemotherapy
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
25-120 hours Complete Remission Rate
Time Frame: 24 hours , 48 hours, 72 hours, 96 hours, 120 hours after chemotherapy
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
0-120h No Nausea Rate
Time Frame: 24 hours, 48 hours, 72 hours, 96 hours, 120 hours after chemotherapy
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fifth Affiliated Hospital, Sun Yat-Sen University

Investigators

  • Study Director: Zhigang Liu, M.D., Fifth Affilliated Hospital of Sun Yat-sen University
  • Principal Investigator: Zhigang Liu, M.D., Fifth Affilliated Hospital of Sun Yat-sen University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 3, 2020

Primary Completion (Actual)

May 1, 2022

Study Completion (Actual)

July 1, 2022

Study Registration Dates

First Submitted

June 16, 2020

First Submitted That Met QC Criteria

June 17, 2020

First Posted (Actual)

June 18, 2020

Study Record Updates

Last Update Posted (Actual)

July 29, 2022

Last Update Submitted That Met QC Criteria

July 26, 2022

Last Verified

May 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • No.ZDWY[2020]LunziNo.(K01-1)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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