Clinical trial NCT04536558: 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
Official title: 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（OFFER）
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Solid Tumor Patients Receiving High Emetic Risk Multi-day Chemotherapy
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
Collaborators: name: Jiangsu Hansoh Pharmaceutical Co., Ltd.
First posted: 2020-09-02
Enrollment: 352
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: SUPPORTIVE_CARE

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.

Eligibility criteria: Inclusion Criteria: (abbreviated)

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: (abbreviated)

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;

Primary outcomes:
measure: Complete response (CR) during overall phase
timeFrame: Day 1 to day 8 after highly emetogenic chemotherapy initiation
Secondary outcomes:
measure: Complete response (CR) during acute phase
timeFrame: Day 1 to day 3 days after highly emetogenic chemotherapy initiation
measure: Complete response (CR) during delayed phase
timeFrame: Day 4 to day 8 after highly emetogenic chemotherapy initiation
measure: No significant nausea during overall phase using questionnaire
timeFrame: Day 1 to day 8 after highly emetogenic chemotherapy initiation
measure: No significant nausea during acute phase using questionnaire
timeFrame: Day 1 to day 3 after highly emetogenic chemotherapy initiation
measure: No significant nausea during delayed phase using questionnaire
timeFrame: Day 4 to day 8 after highly emetogenic chemotherapy initiation
measure: To compare quality of life using the functional living index-emesis questionnaire
timeFrame: From baseline to day 8 after highly emetogenic chemotherapy initiation
measure: To compare olanzapine plus fosaprepitant regimen with placebo plus fosaprepitant regimen in terms of the number of days to first emetic episode.
timeFrame: Day 1 to day 8 after highly emetogenic chemotherapy initiation
measure: To compare the number of participants with treatment-related adverse events as assessed by CTCAE v4.0
timeFrame: From baseline to day 8 after highly emetogenic chemotherapy initiation
measure: To compare the change of score using Hospital Anxiety and Depression Scale
timeFrame: From baseline to day 8 after highly emetogenic chemotherapy initiation
Other outcomes:
measure: The plasma concentration of 5-hydroxytryptamine and substance P at the baseline
timeFrame: From baseline to day 8 after highly emetogenic chemotherapy initiation
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Beijing
country: China
facility: Cancer Hospital Chinese Academy of Medical Sciences
city: Changsha
country: China
facility: Hunan Cancer Hospital
city: Chengdou
country: China
facility: Sichuan Cancer Hospital& Institute
city: Chongqing
country: China
facility: The First Affiliated Hospital of Chongqing Medical University
city: Guangdong
country: China
facility: Sun Yat-sen University Cancer Center
city: Haerbin
country: China
facility: Harbin Medical University Cancer Hospital
city: Hefei
country: China
facility: Anhui Provincial Cancer Hospital
city: Kunming
country: China
facility: Yunnan Cancer Hospital
city: Nanchang
country: China
facility: Jiangxi Cancer Hospital
city: Nanning
country: China
facility: Guangxi Medical University Affiliated Tumor Hospital
city: Ningbo
country: China
facility: Ningbo Medical Center Lihuili Hospital
city: Shanghai
country: China
facility: Shanghai Sixth People's Hospital Affiliated to Shanghai JiaoTong University
city: Shenyang
country: China
facility: Liaoning Cancer Hospital & Institute
city: Shijiazhuang
country: China
facility: Fourth Hospital of Hebei Medical University
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University
city: Tianjin
country: China
facility: Tianjin Medical University General Hospital
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
Study officials:
References: