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

Chemotherapy-induced Nausea and Vomiting Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06331520
• Other study ID #: Desineo
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: May 1, 2024
• Est. completion date: May 1, 2026

Study information

• Verified date: March 2024
• Source: Fudan University
• Contact: Jian Zhang, MD,PhD
• Phone: +8664175590
• Email: syner2000[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 627
• Est. completion date: May 1, 2026
• Est. primary completion date: May 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Chemotherapy-induced Nausea and Vomiting
• Nausea
• Vomiting

Intervention

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]).
• 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.
• Dexamethasone Oral
synthetic glucocorticoids

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Fudan University

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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
Secondary	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
Secondary	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
Secondary	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