NEPA Combined With Olanzapine, Dexamethasone-sparing for the Effect of CINV in Patients Receiving HEC Regimens

Dexamethasone-sparing Based on Netupitant/Palonosetron(NEPA) With Olanzapine for the Effect of Chemotherapy-induced Nausea and Vomiting in Patients Receiving Highly Emetogenic Chemotherapy: a Randomized Noninferiority III Phase Trial

The objective of this Prospective, randomized, non inferiority phase III trial is to confirm the efficacy and saftey of dexamethasone-sparing combined with netupitant/palonostron and olanzapine for the prevention of chemotherapy-induced nausea and vomiting in patients receiving highly emetogenic chemotherapy.

Study Overview

• Status: Not yet recruiting
• Conditions: Chemotherapy-induced Nausea and Vomiting; Highly Emetogenic Chemotherapy
• Intervention / Treatment: Drug: Netupitant / Palonosetron Oral Capsule [Akynzeo]; Drug: Olanzapine; Drug: Dexamethasone Oral

• Study Type: Interventional
• Enrollment (Estimated): 627
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Jian Zhang, MD,PhD; Phone Number: 85000 +8664175590; Email: syner2000@163.com
• Study Contact Backup: Name: Yanchun Meng, MD; Phone Number: 85000 +8664175590; Email: ycmclinicaltrials@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female patients ≥18 years old
2. Patients who receive the high-emetic-risk anticancer agents.
3. Patients who do not take a medicine, for example, 5HT3 receptor antagonists, NK1 receptor antagonists, or research related agents, within 3 weeks prior to enrollment.
4. No nausea or vomiting (grade II or above) within 72 hours before the start of chemotherapy.
5. Subject has Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
6. Subject has a life Expectation of at least 12 weeks.
7. In accordance with the indication of chemotherapy and basic requirements： Peripheral haematology: Hb ≥9.0g/dL; absolute neutrophil count ≥1.5×109/L; Platelet count ≥80×109/L Blood biochemistry: Total bilirubin < 1.25×ULN, ALT and AST ≤ 2.5×ULN; If liver metastasis, ALT and AST < 5×ULN, Creatinine ≤ 1×ULN, basic normal serum electrolyte (Na, Ka, Cl, Ca) Other important organs function normally.
8. Female patients of either non-childbearing potential or child-bearing potential use contraceptive methods throughout the clinical trial.
9. Female patients with child-bearing potential must is negative of pregnancy test.
10. Subjects voluntarily and strictly comply with the research protocol requirements and sign a written informed consent
11. Subjects can independently fill out patient diaries.

Exclusion Criteria:

1. Patients receiving moderate or high emetic radioation therapy within 1 week before chemotherapy or day 1 to 5 after chemotherapy.
2. Within 24 hours after chemotherapy, patients receiving any known or potential antiemetic agents and appearing symptoms vomiting, nausea, or mild nausea symptoms.
3. Scheduled to receive inducer or substrate or strong / moderate inhibitor of cytocrome P450 3A4 (CYP3A4) within 3 weeks prior to day 1.
4. Patients who cannot tolerate chemotherapy drugs.
5. Serious cardiovascular, pulmonary disease, diabetes, mental and other diseases.
6. Pregnant , breastfeeding and woman with child-bearing potential who are unwilling or unable to take effective contraceptive measures.
7. Drug addict or alcohol abuse.
8. Hypocalcemia or any other condition that may cause vomiting.
9. Patients has significant factors that affect the absorption of oral medication, such as chronic diarrhea or obstruction.
10. Subjects has hypersensitivity to netupitant/palonostron capsules or any of its excipients.
11. Scheduled to receive any antiemetic agents within 3 weeks prior to day 1(including but not limited to: neurokin-1 (NK1) receptor antagonist, 5-HT3 receptor antagonists, olanzapine, scopolamine,et al.).
12. Scheduled to receive benzodiazepine, opioid or opioid derivatives (except midazolam, temazepam or triazolam)within 1 week before chemotherapy or day 1 to 5 after chemotherapy.
13. Subjects are currently enrolled in an other clinical study with any other clinical trials, investigational drugs or observational studies within 21 days of baseline.
14. Investigators judged other situations that may affect the progress and results of clinical research.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: NEO-DXMS GROUP; NEPA(1 capsule, day1, PO)+ Olanzapine(5mg, day1-4, PO)+ dexamethasone(12mg, day1; 8mg day2-4, PO/IV).	Drug: Netupitant / Palonosetron Oral Capsule [Akynzeo]; Akynzeo is the fixed-combination antiemetic comprising netupitant (neurokinin-1 receptor antagonist [NK1 RA]) and palonosetron (5-hydroxytryptamine-3 receptor antagonist [5-HT3 RA]).; Drug: Olanzapine; Olanzapine is an effective antipsychotic drug used in psychiatry to treat psychoses, especially schizophrenia and schizoaffective disorders. It belongs to the 2nd generation antipsychotics, its mechanism of action ranks among multireceptor antagonists (MARTA); it affects the dopamine, serotonin, adrenaline, histamine, and muscarinic systems.; Drug: Dexamethasone Oral; synthetic glucocorticoids
Active Comparator: HALF-DXMS GROUP; NEPA(1 capsule, day1, PO)+ Olanzapine(5mg, day1-4, PO)+ dexamethasone(6mg, day1, PO/IV)	Drug: Netupitant / Palonosetron Oral Capsule [Akynzeo]; Akynzeo is the fixed-combination antiemetic comprising netupitant (neurokinin-1 receptor antagonist [NK1 RA]) and palonosetron (5-hydroxytryptamine-3 receptor antagonist [5-HT3 RA]).; Drug: Olanzapine; Olanzapine is an effective antipsychotic drug used in psychiatry to treat psychoses, especially schizophrenia and schizoaffective disorders. It belongs to the 2nd generation antipsychotics, its mechanism of action ranks among multireceptor antagonists (MARTA); it affects the dopamine, serotonin, adrenaline, histamine, and muscarinic systems.; Drug: Dexamethasone Oral; synthetic glucocorticoids
Experimental: NEO GROUP; NEPA(1 capsule, day1, PO)+ Olanzapine(5mg, day1-4, PO).	Drug: Netupitant / Palonosetron Oral Capsule [Akynzeo]; Akynzeo is the fixed-combination antiemetic comprising netupitant (neurokinin-1 receptor antagonist [NK1 RA]) and palonosetron (5-hydroxytryptamine-3 receptor antagonist [5-HT3 RA]).; Drug: Olanzapine; Olanzapine is an effective antipsychotic drug used in psychiatry to treat psychoses, especially schizophrenia and schizoaffective disorders. It belongs to the 2nd generation antipsychotics, its mechanism of action ranks among multireceptor antagonists (MARTA); it affects the dopamine, serotonin, adrenaline, histamine, and muscarinic systems.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of patients with complete response (CR)	Percentage of patients with complete response (CR) defined defined as no vomiting with no use of rescue therapy	Within 0-120 hours from the initiation of chemotherapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Patients With CR (acute and delayed)	Percentage of patients with complete response (CR) defined defined as no vomiting with no use of rescue therapy "Acute"period referred to 0-24 h after the initiation of chemotherapy,"delayed"period referred to 24-120 h.	From the initiation of chemotherapy infusion(0h)up to beginning of day 6(-120 h)
Percentage of patients with overall complete protection(OCP)	Percentage of patients with overall complete protection(OCP) defined as no emesis, no rescue medication and able mild nausea(VAS≤25mm).	During the acute (within 24 hours post-chemotherapy) and delayed (days 2 thorough 5) phases of chemotherapy
Percentage of patients with overall total control (OTC)	Percentage of patients with overall total control (OTC) defined as no emesis, no rescue medication and no nausea(VAS≤5mm).	During 0 ~ 24 hours and 0 ~ 168 hours post-chemotherapy
incidence of adverse events	Adverse event s were graded according to NCI CTCAE v 5.0	From initiation of chemotherapy to 168 hours after initiation of chemotherapy
quality of life questionnaire	Quality of life(QoL) was evaluated by the Chinese version of the self reported Functional Living Index-Emesis (FLIE) questionnaire by individual patients.	From initiation of chemotherapy to 168 hours after initiation of chemotherapy

Collaborators and Investigators

• Sponsor: Fudan University

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): May 1, 2025
• Study Completion (Estimated): May 1, 2026

Study Registration Dates

• First Submitted: January 29, 2024
• First Submitted That Met QC Criteria: March 25, 2024
• First Posted (Actual): March 26, 2024

Study Record Updates

• Last Update Posted (Actual): March 26, 2024
• Last Update Submitted That Met QC Criteria: March 25, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Nausea; Vomiting; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Serotonin Antagonists; Serotonin 5-HT3 Receptor Antagonists; Selective Serotonin Reuptake Inhibitors; Dexamethasone; Olanzapine; Palonosetron
• Other Study ID Numbers: Desineo

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No