NEPA to Prevent Chemotherapy Induced Nausea and Vomiting in Patients With Breast Cancer

Study Overview
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Brief Summary
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This study evaluates if the activity of one-day of NEPA plus dexamethasone, to prevent chemotherapy-induced nausea and vomiting in breast cancer patients receiving adjuvant AC-based chemotherapy, is maintained during all the chemotherapy cycle treatment (maximum 4 cycles).

Detailed Description
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Patients included in the study should be treated with the following antiemetic prophylaxis, during all the AC-based chemotherapy cycles, up to a maximum of 4 cycles: NEPA will be administered orally at the dose of 300 mg netupitant/0.5 palonosetron 1 hour before the start of any chemotherapy cycle. Dexamethasone 12 mg will be added on day 1 only of each cycle.

Official Title
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One Day Antiemetic Prophylaxis of NEPA (Netupitant Plus Palonosetron) and Dexamethasone to Prevent Chemotherapy-induced Nausea and Vomiting (CINV) in Breast Cancer Patients Receiving an AC-based Chemotherapy Regimen

Conditions
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Chemotherapy-induced Nausea and Vomiting

Intervention / Treatment
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* Drug: Netupitant/Palonosetron


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women ≥ 18 years old Histologically or cytologically confirmed diagnosis of breast cancer Naïve patients Be scheduled to receive adjuvant chemotherapy with anthracycline (doxorubicin or epirubicin) + cyclophosphamide (AC-based regimen) ECOG (Eastern Cooperative Oncology Group) performance status 0-2 Body Mass index (BMI) ≥ 18.5 Written informed consent If women of childbearing potential age: reliable contraceptive measures must be used during the study treatment period and up to 30 days after last NEPA administration Acceptable hepatic function (<= 2 times the upper limit of normal for liver transaminases) and renal function (creatinine < 1.5 times the upper limit of normal); Ability and willingness of the patient to complete the diary. Exclusion Criteria: Advanced/metastatic breast cancer Patients already submitted to non-AC-based chemotherapy Treatment with investigational medications in 30 days before NEPA Myocardial infarction within the last 6 months Documented or known hypersensitivity to 5HT3RA (5-Hydroxytryptamine Receptor 3 Antagonists) or NK1RA (Neurokinin-1 Receptor Antagonists) and excipients Uncontrolled diabetes mellitus Nausea and vomiting at baseline Chronic use of other antiemetic agent(s) Patient's inability to take oral medication Gastrointestinal obstruction or active peptic ulcer Pregnancy or breastfeeding Prior malignancies at other sites except surgically treated non-melanoma skin cancer, superficial cervical cancer, or other cancer from which the patient had been disease-free for ≥ 5 years Psychiatric or CNS (Central Nervous System) disorders interfering with ability to comply with study protocol

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Interventional Model Description: Phase II study, one stage Fleming design, open-label, multicenter, not comparative
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Netupitant/Palonosetron & Dexamethasone<br>Netupitant/Palonosetron (NEPA) will be administered orally at the dose of 300 MG (milligrams) netupitant/0.5 palonosetron 1 hour before the start of any chemotherapy cycle. Dexamethasone 12 mg will be added on day 1 only of each cycle. | Drug: Netupitant/Palonosetron<br> <br> * Other names: Netupitant/Palonosetron 300 MG-0.5 MG Oral Capsule [AKYNZEO];|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response | The rate of patients achieving and maintaining a complete response (defined as no emetic episode and no use of rescue medication) during the overall phase of all AC-based chemotherapy cycles | During the overall phase (From day 1 to day 5 after any AC-based chemotherapy administration) for a maximum 4 cycles (each cycle is 21 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute and Delayed Phase Complete Response | Rate of complete control (defined as no emetic episode and no need for rescue medication) | During the Acute Phase [0-24 hours after chemotherapy (CT)] and the Delayed (25-120 hours) phase | 
| Complete Control | Rate of complete control (defined as complete response with a maximum grade of mild nausea) | During the Acute Phase (0-24 hours after chemotherapy), the Delayed (25-120 hours), the Overall (0-120 hours) phases for each cycle and separately on single days of all chemotherapy cycles (each cycle is 21 days), up to 4 cycles | 
| Emesis-Free | Percentage of emesis-free patients (no emetic episodes) after any AC-based chemotherapy administration. | During the Acute (0-24 hours after CT), the Delayed (25-120 hours), the Overall (0-120 hours) phases for each cycle (each cycle is 21 days)and separately on single days of all CT cycles,up to 4 cycles.Also during the period between two consecutive cycles | 
| Nausea | Presence of nausea graded according to Likert scale (none, mild, moderate and severe) | During the Acute (0-24 hours after CT), the Delayed (25-120 hours), the Overall (0-120 hours) phases for each cycle (of 21 days)and separately on single days of all chemotherapy cycles, up to 4 cycles.Also during the period between two consecutive cycles | 
| Global satisfaction with antiemetic therapy: Visual Analogue Scale (VAS) | Patient global satisfaction with antiemetic therapy, as measured by a Visual Analogue Scale (VAS). Scale ranges are 0-10 (0 represents maximum dissatisfaction, 10 represents maximum satisfaction) | During the Acute Phase (0-24 hours after CT), the Delayed (25-120 hours), the Overall (0-120 hours) phases for each cycle (each cycle is 21 days) and separately on single days of all CT cycles, up to 4 cycles | 
| Safety profile (according to CTCAE) | Safety profile according to CTCAE | During the Acute Phase (0-24 hours after CT), the Delayed (25-120 hours), the Overall (0-120 hours) phases for each cycle (each cycle is 21 days) and separately on single days of all CT cycles, up to 4 cycles | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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nausea, vomiting, breast cancer, AC-based chemotherapy