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

NCT ID: NCT06331520

Last Updated: 2024-03-26

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 627 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-05-01
• Study Completion Date: 2026-05-01

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.

Conditions

Chemotherapy-induced Nausea and Vomiting; Highly Emetogenic Chemotherapy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

NEO-DXMS GROUP

NEPA(1 capsule, day1, PO)+ Olanzapine(5mg, day1-4, PO)+ dexamethasone(12mg, day1; 8mg day2-4, PO/IV).

Group Type: ACTIVE_COMPARATOR

Netupitant / Palonosetron Oral Capsule [Akynzeo]

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

synthetic glucocorticoids

HALF-DXMS GROUP

NEPA(1 capsule, day1, PO)+ Olanzapine(5mg, day1-4, PO)+ dexamethasone(6mg, day1, PO/IV)

Group Type: ACTIVE_COMPARATOR

Netupitant / Palonosetron Oral Capsule [Akynzeo]

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

synthetic glucocorticoids

NEO GROUP

NEPA(1 capsule, day1, PO)+ Olanzapine(5mg, day1-4, PO).

Group Type: EXPERIMENTAL

Netupitant / Palonosetron Oral Capsule [Akynzeo]

Intervention Type: DRUG

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

Intervention Type: DRUG

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.

Interventions

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 \[5-HT3 RA\]).

Intervention Type: 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.

Intervention Type: DRUG

Dexamethasone Oral

synthetic glucocorticoids

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fudan University

OTHER

Sponsor Role: lead

Responsible Party

Jian Zhang,MD

Director of Phase I Clinical Trial Department; Professor, Chief physician of oncology department

Responsibility Role: PRINCIPAL_INVESTIGATOR

Central Contacts

Jian Zhang, MD,PhD

Role: CONTACT

syner2000@163.com

+8664175590 ext. 85000

Yanchun Meng, MD

Role: CONTACT

ycmclinicaltrials@126.com

+8664175590 ext. 85000

Other Identifiers

Desineo

Identifier Type: -

Identifier Source: org_study_id