Olanzapine Plus Fosaprepitant Standard Antiemetic Therapy in the Prevention of Chemotherapy-induced Nausea and Vomiting in Patients Receiving High Emetic Risk Multi-day Chemotherapy: a Multicenter, Randomized, Double-blind, Placebo-controlled, Phase 3 Study

NCT ID: NCT04536558

Last Updated: 2020-09-02

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 352 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-10-01
• Study Completion Date: 2021-03-30

Brief Summary

This is a multicenter, randomized, controlled, double-blind, phase III study.

Detailed Description

This is a multicenter, randomized, controlled, double-blind, phase III study assessing the efficacy and safety of Olanzapine plus fosaprepitant plus ondansetron and dexamethasone versus fosaprepitant plus ondansetron and dexamethasone in the prevention of chemotherapy-induced nausea and vomiting in patients receiving high emetic risk multi-day chemotherapy. Eligible patients will be randomized to receive either olanzapine plus fosaprepitant standard antiemetic therapy or fosaprepitant standard antiemetic therapy in a 1:1 ratio.

Conditions

Solid Tumor Patients Receiving High Emetic Risk Multi-day Chemotherapy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: DOUBLE

Study Groups

olanzapine plus fosaprepitant-based triple regimen

Olanzapine（5mg p.o. d1-d5）plus fosaprepitant（150mg i.v. d1-d3） plus ondansetron（8mg i.v. d1-d3）and dexamethasone（6mg p.o. d1-d5） before undergoing chemotherapy.

Group Type: EXPERIMENTAL

olanzapine plus fosaprepitant-based triple regimen

Intervention Type: DRUG

olanzapine 5mg p.o. on day 1-day 5, fosaprepitant 150mg i.v. on day 1 before undergoing chemotherapy. Patients received ondansetron hydrochloride(8mg, i.v. day 1-day 3) and dexamethasone(6mg, oral, day 1-day 5) at the same time, before undergoing chemotherapy.

Placebo plus fosaprepitant-based triple regimen

Placebo plus fosaprepitant（150mg i.v. d1-d3） plus ondansetron（8mg i.v. d1-d3）and dexamethasone（6mg p.o. d1-d5） before undergoing chemotherapy.

Group Type: PLACEBO_COMPARATOR

placebo plus fosaprepitant-based triple regimen

Intervention Type: DRUG

placebo p.o. on day 1-day 5, fosaprepitant 150mg i.v. on day 1 before undergoing chemotherapy. Patients received ondansetron hydrochloride(8mg, i.v. day 1-day 3) and dexamethasone(6mg, oral, day 1-day 5) at the same time, before undergoing chemotherapy.

Interventions

olanzapine plus fosaprepitant-based triple regimen

olanzapine 5mg p.o. on day 1-day 5, fosaprepitant 150mg i.v. on day 1 before undergoing chemotherapy. Patients received ondansetron hydrochloride(8mg, i.v. day 1-day 3) and dexamethasone(6mg, oral, day 1-day 5) at the same time, before undergoing chemotherapy.

Intervention Type: DRUG

placebo plus fosaprepitant-based triple regimen

placebo p.o. on day 1-day 5, fosaprepitant 150mg i.v. on day 1 before undergoing chemotherapy. Patients received ondansetron hydrochloride(8mg, i.v. day 1-day 3) and dexamethasone(6mg, oral, day 1-day 5) at the same time, before undergoing chemotherapy.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Male and female patients aged ≥ 18 and ≤ 75 years old;

2. Patients were diagnosed with histologically or cytology confirmed solid malignant tumors;

3. Patients have a Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2;

4. Patients were predicted life expectancy of ≥ 3 months;

5. Patients who were scheduled for 3 days of cisplatin based chemotherapy.

Exclusion Criteria

1. Patients were mentally disable or suffered from emotional disorders;

2. Patients were current illicit drug use, including alcohol abuse;

3. Patients scheduled administration of stem cell rescue therapy during cisplatin chemotherapy;

4. Patients have participated in other clinical trials in the past 4 weeks;

5. Patients were treated with chemotherapy including ordinary paclitaxel(using castor oil as a solvent);

6. Patients with active infections (e.g., pneumonia) or any uncontrolled disease (e.g., diabetic ketoacidosis, gastrointestinal obstruction) other than malignant tumors, and the researchers believe that it may confound the results of the study or expose patients receiving treatment with the study drug at unnecessary risk;

7. Patients have any disease that the researcher believes may confound the results of the study or expose the patient to unnecessary risk；

8. Patients were treated with moderate or highly emetogenic chemotherapy within 6 days prior to the initial of cisplatin infusion and/or 6 days after cisplatin infusion;

9. Patients were scheduled to receive radiation therapy to the abdomen or pelvis within a week of treatment;

10. Absolute neutrophil count<1,500 cells/ L, white blood cell count<3,000 cells/ L, platelet count<100,000 cells/ L, aspartate aminotransferase and alanine aminotransferase>2.5 upper limit of normal (ULN), bilirubin > 1.5 ULN, and creatinine > 1.5 ULN;

11. Patients were pregnant or breastfeeding;

12. Patients had suffered from vomiting or nausea in the 24 hours before treatment;

13. Patients were known to be at risk for narrow angle glaucoma；

14. Patients who are taking or have used CYP3A4 inducers within 30 days before the first day of treatment, which will affect the efficacy of the treatment drugs according to the researcher's evaluation, can not be enrolled;

15. Patients who are taking or have used CYP3A4 substrates and inhibitors within 7 days before the first day of treatment will significantly increase the treatment drug-related adverse events according to the researcher's evaluation, can not be enrolled;

16. Within 48 hours before the first day of treatment, patients used the following antiemetic agents: 5-hydroxytryptamine 3 receptor antagonists (such as ondansetron), phenothiazines (such as prochlorperazine), benzophenones (such as haloperidol), benzamide (such as metoclopramide), domperidone, cannabinoids, herbs with potential antiemetic effects, scopolamine, and cyclizine, etc;

17. Patients began to receive benzodiazepines or opioids within 48 hours prior to the first day of the study (except for triazolam, temazepam or midazolam single dose daily);

18. Patients had symptomatic primary or metastatic central nervous system malignancies;

19. Patients had concomitant diseases that could not take dexamethasone for 5 days, such as systemic fungal infection or uncontrolled diabetes mellitus;

20. Patients were not allowed to receive any dose of systemic glucocorticoid therapy within 72 hours before the first day except those prescribed in the protocol; however, local and inhaled corticosteroids were allowed;

21. Patients had a history of hypersensitivity to fosaprepitant meglumine, olanzapine, ondansetron or dexamethasone；

22. Patients had been treated with neurokinin-1 receptor antagonist in the past;

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

Sponsors

Jiangsu Hansoh Pharmaceutical Co., Ltd.

INDUSTRY

Sponsor Role: collaborator

Sun Yat-sen University

OTHER

Sponsor Role: lead

Responsible Party

Li Zhang, MD

head of the medical department

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Beijing Cancer Hospital

Beijing, , China

Cancer Hospital Chinese Academy of Medical Sciences

Beijing, , China

Hunan Cancer Hospital

Changsha, , China

Sichuan Cancer Hospital& Institute

Chengdoucun, , China

The First Affiliated Hospital of Chongqing Medical University

Chongqing, , China

Sun Yat-sen University Cancer Center

Guangdong, , China

Harbin Medical University Cancer Hospital

Haerbin, , China

Anhui Provincial Cancer Hospital

Hefei, , China

Yunnan Cancer Hospital

Kunming, , China

Jiangxi Cancer Hospital

Nanchang, , China

Guangxi Medical University Affiliated Tumor Hospital

Nanning, , China

Ningbo Medical Center Lihuili Hospital

Ningbo, , China

Shanghai Sixth People's Hospital Affiliated to Shanghai JiaoTong University

Shanghai, , China

Liaoning Cancer Hospital & Institute

Shenyang, , China

Fourth Hospital of Hebei Medical University

Shijiazhuang, , China

The First Affiliated Hospital of Soochow University

Suzhou, , China

Tianjin Medical University General Hospital

Tianjin, , China

Henan Cancer Hospital

Zhengzhou, , China

Countries

China

Central Contacts

Li Zhang

Role: CONTACT

zhangli@sysucc.org.cn

+86 20-87342288

Facility Contacts

Jian Fang

Role: primary

Jianchun Duan

Role: primary

Lin Wu

Role: primary

Wenxiu Yao

Role: primary

Xiaopin Chen

Role: primary

Li Zhang

Role: primary

Li Cai

Role: primary

Changlu Hu

Role: primary

Runxiang Yang

Role: primary

Yinglan Chen

Role: primary

Qitao Yu

Role: primary

Daliu Min

Role: primary

Tao Sun

Role: primary

Junfeng Liu

Role: primary

Kai Chen

Role: primary

Diansheng Zhong

Role: primary

Yanqiu Zhao

Role: primary

References

Zhao Y, Yang Y, Gao F, Hu C, Zhong D, Lu M, Yuan Z, Zhao J, Miao J, Li Y, Zhu J, Wang C, Han J, Zhao Y, Huang Y, Zhang L. A multicenter, randomized, double-blind, placebo-controlled, phase 3 trial of olanzapine plus triple antiemetic regimen for the prevention of multiday highly emetogenic chemotherapy-induced nausea and vomiting (OFFER study). EClinicalMedicine. 2022 Dec 15;55:101771. doi: 10.1016/j.eclinm.2022.101771. eCollection 2023 Jan.

Reference Type: DERIVED

PMID: 36712888 (View on PubMed)

Other Identifiers

HS-TN-001

Identifier Type: -

Identifier Source: org_study_id