Clinical trial NCT03862144: NEPA to Prevent Chemotherapy Induced Nausea and Vomiting in Patients With Breast Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chemotherapy-induced Nausea and Vomiting
Keywords: nausea
vomiting
breast cancer
AC-based chemotherapy
Lead sponsor: Consorzio Oncotech
Sponsor class: OTHER
First posted: 2019-03-05
Enrollment: 150
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Phase II study, one stage Fleming design, open-label, multicenter, not comparative
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Complete response
timeFrame: 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 outcomes:
measure: Acute and Delayed Phase Complete Response
timeFrame: During the Acute Phase [0-24 hours after chemotherapy (CT)] and the Delayed (25-120 hours) phase
measure: Complete Control
timeFrame: 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
measure: Emesis-Free
timeFrame: 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
measure: Nausea
timeFrame: 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
measure: Global satisfaction with antiemetic therapy: Visual Analogue Scale (VAS)
timeFrame: 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
measure: Safety profile (according to CTCAE)
timeFrame: 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
Other outcomes:
Locations:
Study officials:
affiliation: National Cancer Institute "Fondazione Pascale", Naples
name: Michelino De Laurentiis, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.