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

NCT04437017 | Completed Phase 3

• 1 other identifier: No.ZDWY[2020]LunziNo.(K01-1)
• Study Type: interventional
• Target: 557
• Locations: 1 country
• Sites: 1

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

Keywords

nausea; vomiting; antiemesis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• 25-120 hours Complete Remission Rate

  24 hours , 48 hours, 72 hours, 96 hours, 120 hours after chemotherapy

• 0-120h No Nausea Rate

  24 hours, 48 hours, 72 hours, 96 hours, 120 hours after chemotherapy

Study Arms (2)

Olanzapine+NK-1 RA+5-HT3 RA

EXPERIMENTAL

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

Dexamethasone+NK-1 RA+5-HT3 RA

ACTIVE COMPARATOR

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

Interventions

Olanzapine+NK-1 RA+5-HT3 RA DRUG

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

Olanzapine+NK-1 RA+5-HT3 RA

Dexamethasone+NK-1 RA+5-HT3 RA 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.

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

Dexamethasone+NK-1 RA+5-HT3 RA

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• Life expectancy ≥ 3 months;
• Leucocytes≥3,000/uL;
• AST≤2.5 × upper limit of normal;
• Bilirubin ≤1.5 × upper limit of normal;
• Serum creatinine ≤ 1.5 × upper limit of normal.

You may not qualify if:

• History of CNS disease, such as brain metastases or epilepsy;
• 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;
• Concurrent use of pharyngeal or abdominal radiotherapy;
• Concurrent use of quinolone antibiotics;
• Chronic alcoholism;
• Known hypersensitivity to olanzapine;
• Know arrhythmia, uncontrolled congestive heart failure or acute myocardial infarction within 6 months;
• Known uncontrolled diabetes mellitus;
• Vomiting or retching 24 hours before chemotherapy;
• Use of anti-emesis drugs 48 hours before chemotherapy;
• Concurrent use of amifostine;
• Concurrent use of corticosteroids and the only anti-allergic choice is corticosteroids

Sponsors & Collaborators

• Fifth Affiliated Hospital, Sun Yat-Sen University: lead

Study Sites (1)

Fifth Affilliated Hospital of Sun Yat-sen University

Zhuhai, Guangdong, China

Location

MeSH Terms

Conditions

Vomiting; Nausea

Interventions

Calcium Dobesilate; Fluprednisolone

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Zhigang Liu, M.D.

  Fifth Affilliated Hospital of Sun Yat-sen University

  STUDY DIRECTOR

• Zhigang Liu, M.D.

  Fifth Affilliated Hospital of Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice Director

Study Record Dates

• First Submitted: June 16, 2020
• First Posted: June 18, 2020
• Study Start: February 3, 2020
• Primary Completion: May 1, 2022
• Study Completion: July 1, 2022
• Last Updated: July 29, 2022

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)