NEPA to Prevent Chemotherapy Induced Nausea and Vomiting in Patients With Breast Cancer (GIM15-NEPA)

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

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).

Study Overview

• Status: Completed
• Conditions: Chemotherapy-induced Nausea and Vomiting
• Intervention / Treatment: Drug: Netupitant/Palonosetron

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 150
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Women ≥ 18 years old
2. Histologically or cytologically confirmed diagnosis of breast cancer
3. Naïve patients
4. Be scheduled to receive adjuvant chemotherapy with anthracycline (doxorubicin or epirubicin) + cyclophosphamide (AC-based regimen)
5. ECOG (Eastern Cooperative Oncology Group) performance status 0-2
6. Body Mass index (BMI) ≥ 18.5
7. Written informed consent
8. 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
9. 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);
10. Ability and willingness of the patient to complete the diary.

Exclusion Criteria:

1. Advanced/metastatic breast cancer
2. Patients already submitted to non-AC-based chemotherapy
3. Treatment with investigational medications in 30 days before NEPA
4. Myocardial infarction within the last 6 months
5. Documented or known hypersensitivity to 5HT3RA (5-Hydroxytryptamine Receptor 3 Antagonists) or NK1RA (Neurokinin-1 Receptor Antagonists) and excipients
6. Uncontrolled diabetes mellitus
7. Nausea and vomiting at baseline
8. Chronic use of other antiemetic agent(s)
9. Patient's inability to take oral medication
10. Gastrointestinal obstruction or active peptic ulcer
11. Pregnancy or breastfeeding
12. 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
13. Psychiatric or CNS (Central Nervous System) disorders interfering with ability to comply with study protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Netupitant/Palonosetron & Dexamethasone; 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; Other Names: Netupitant/Palonosetron 300 MG-0.5 MG Oral Capsule [AKYNZEO]

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Consorzio Oncotech
• Investigators: Principal Investigator: Michelino De Laurentiis, MD, PhD, National Cancer Institute "Fondazione Pascale", Naples

Publications and helpful links

General Publications

• Caputo R, Cazzaniga ME, Sbrana A, Torrisi R, Paris I, Giordano M, Montesarchio V, Guarneri V, Amaducci L, Bilancia D, Cilenti G, Fabi A, Collova E, Schirone A, Bonizzoni E, Celio L, De Placido S, De Laurentiis M. Netupitant/palonosetron (NEPA) and dexamethasone for prevention of emesis in breast cancer patients receiving adjuvant anthracycline plus cyclophosphamide: a multi-cycle, phase II study. BMC Cancer. 2020 Mar 19;20(1):232. doi: 10.1186/s12885-020-6707-9.

Study record dates

Study Major Dates

• Study Start (Actual): May 12, 2016
• Primary Completion (Actual): April 3, 2017
• Study Completion (Actual): April 3, 2017

Study Registration Dates

• First Submitted: January 14, 2019
• First Submitted That Met QC Criteria: March 1, 2019
• First Posted (Actual): March 5, 2019

Study Record Updates

• Last Update Posted (Actual): March 5, 2019
• Last Update Submitted That Met QC Criteria: March 1, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: breast cancer; nausea; vomiting; AC-based chemotherapy
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Nausea; Vomiting; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Serotonin Agents; Serotonin Antagonists; Serotonin 5-HT3 Receptor Antagonists; Palonosetron
• Other Study ID Numbers: GIM15-NEPA