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

Phase 3

Not yet recruiting

• Conditions: Chemotherapy-induced Nausea and Vomiting; Highly Emetogenic Chemotherapy
• Interventions: Drug: Netupitant / Palonosetron Oral Capsule [Akynzeo]; Drug: Olanzapine; Drug: Dexamethasone Oral

• Registration Number: NCT06331520
• Lead Sponsor: Fudan University

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-01-29
• Status Verified: 2024-03
• Study First Submitted QC: 2024-03-25
• Last Update Submitted: 2024-03-25
• Study First Posted: 2024-03-26
• Last Update Posted: 2024-03-26
• Study Start: 2024-05-01
• Primary Completion: 2025-05-01
• Study Completion: 2026-05-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 627

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
HALF-DXMS GROUP	Netupitant / Palonosetron Oral Capsule [Akynzeo]	NEPA(1 capsule, day1, PO)+ Olanzapine(5mg, day1-4, PO)+ dexamethasone(6mg, day1, PO/IV)
NEO-DXMS GROUP	Netupitant / Palonosetron Oral Capsule [Akynzeo]	NEPA(1 capsule, day1, PO)+ Olanzapine(5mg, day1-4, PO)+ dexamethasone(12mg, day1; 8mg day2-4, PO/IV).
NEO-DXMS GROUP	Olanzapine	NEPA(1 capsule, day1, PO)+ Olanzapine(5mg, day1-4, PO)+ dexamethasone(12mg, day1; 8mg day2-4, PO/IV).
NEO-DXMS GROUP	Dexamethasone Oral	NEPA(1 capsule, day1, PO)+ Olanzapine(5mg, day1-4, PO)+ dexamethasone(12mg, day1; 8mg day2-4, PO/IV).
HALF-DXMS GROUP	Olanzapine	NEPA(1 capsule, day1, PO)+ Olanzapine(5mg, day1-4, PO)+ dexamethasone(6mg, day1, PO/IV)
HALF-DXMS GROUP	Dexamethasone Oral	NEPA(1 capsule, day1, PO)+ Olanzapine(5mg, day1-4, PO)+ dexamethasone(6mg, day1, PO/IV)
NEO GROUP	Netupitant / Palonosetron Oral Capsule [Akynzeo]	NEPA(1 capsule, day1, PO)+ Olanzapine(5mg, day1-4, PO).
NEO GROUP	Olanzapine	NEPA(1 capsule, day1, PO)+ Olanzapine(5mg, day1-4, PO).

Primary Outcome Measures

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

Secondary Outcome Measures

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