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)

Sun Yat-sen University

Status and phase: Unknown; Phase 3

Conditions: Solid Tumor Patients Receiving High Emetic Risk Multi-day Chemotherapy

Treatments: Drug: placebo plus fosaprepitant-based triple regimen; Drug: olanzapine plus fosaprepitant-based triple regimen

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT04536558

HS-TN-001

Details and patient eligibility

About

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

Full 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.

Enrollment: 352 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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;

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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352 participants in 2 patient groups, including a placebo group

olanzapine plus fosaprepitant-based triple regimen

Experimental group

Description:

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.

Treatment:

Drug: olanzapine plus fosaprepitant-based triple regimen

Placebo plus fosaprepitant-based triple regimen

Placebo Comparator group

Description:

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.

Treatment:

Drug: placebo plus fosaprepitant-based triple regimen