Dexamethasone-sparing Approach Including NEPA Against Emesis Caused by Cisplatin

NCT ID: NCT04201769

Last Updated: 2020-04-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

261 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-11-25

Study Completion Date

2020-04-30

Brief Summary

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This study evaluates the possibility to reduce the total dose of dexamethasone, when administered with NEPA, to prevent chemotherapy-induced nausea and vomiting (CINV) in Non-Small Cell Lung Cancer (NSCLC) patients receiving a cisplatin-based chemotherapy

Detailed Description

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On day 1 (day of chemotherapy), all eligible patients will receive oral NEPA (300 mg netupitant/0.5 mg palonosetron), 60 minutes before chemotherapy, and intravenous dexamethasone 12 mg, 30 minutes before chemotherapy initiation.

For the prevention of delayed CINV, patients will be assigned randomly to one of the following treatment arms:

* Test arm A: no further anti-emetic prophylaxis on days 2 thorough 4;
* Test arm B: oral dexamethasone 4 mg once per day in the morning of days 2 and 3;
* Reference arm C: oral dexamethasone 4 mg twice per day on days 2 thorough 4.

Conditions

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Chemotherapy-induced Nausea and Vomiting

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Phase III, multicenter, randomized, open-label, parallel-group, active-comparator, three-arm, non-inferiority study
Primary Study Purpose

SUPPORTIVE_CARE

Blinding Strategy

NONE

Study Groups

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Arm A

Oral Netupitant/Palonosetron (NEPA) and intravenous Dexamethasone (DEX) on Day 1 of chemotherapy.

No further anti-emetic prophylaxis on days 2 thorough 4.

Group Type EXPERIMENTAL

Netupitant/Palonosetron

Intervention Type DRUG

NEPA is adiministered 60 minutes before chemotherapy, on day 1

Dexamethasone

Intervention Type DRUG

Intravenous dexamethasone 12 mg is administered 30 minutes before chemotherapy initiation, on day 1.

The administration of DEX in the subsequent days (2-4) depends on the randomly assignement to treatment arm

Arm B

Oral Netupitant/Palonosetron (NEPA) and intravenous Dexamethasone (DEX) on Day 1 of chemotherapy.

Oral dexamethasone 4 mg once per day in the morning of days 2 and 3.

Group Type EXPERIMENTAL

Netupitant/Palonosetron

Intervention Type DRUG

NEPA is adiministered 60 minutes before chemotherapy, on day 1

Dexamethasone

Intervention Type DRUG

Intravenous dexamethasone 12 mg is administered 30 minutes before chemotherapy initiation, on day 1.

The administration of DEX in the subsequent days (2-4) depends on the randomly assignement to treatment arm

Arm C

Oral Netupitant/Palonosetron (NEPA) and intravenous Dexamethasone (DEX) on Day 1 of chemotherapy.

Oral dexamethasone 4 mg twice per day on days 2 thorough 4.

Group Type ACTIVE_COMPARATOR

Netupitant/Palonosetron

Intervention Type DRUG

NEPA is adiministered 60 minutes before chemotherapy, on day 1

Dexamethasone

Intervention Type DRUG

Intravenous dexamethasone 12 mg is administered 30 minutes before chemotherapy initiation, on day 1.

The administration of DEX in the subsequent days (2-4) depends on the randomly assignement to treatment arm

Interventions

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Netupitant/Palonosetron

NEPA is adiministered 60 minutes before chemotherapy, on day 1

Intervention Type DRUG

Dexamethasone

Intravenous dexamethasone 12 mg is administered 30 minutes before chemotherapy initiation, on day 1.

The administration of DEX in the subsequent days (2-4) depends on the randomly assignement to treatment arm

Intervention Type DRUG

Other Intervention Names

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Netupitant/Palonosetron 300-0.5 milligrams Oral Capsule [AKYNZEO]

Eligibility Criteria

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Inclusion Criteria

* Patients ≥ 18 years old.
* Histologically or cytologically confirmed diagnosis of NSCLC
* Patients naїve to cisplatin-containing chemotherapy as well as any prior chemotherapy containing either highly or moderately emetogenic agents given for NSCLC or other malignancy.
* Patients scheduled to receive their first cycle of cisplatin-based chemotherapy at a dose ≥70 mg/m2 either alone or in combination with other agents of low or minimal potential of emetogenicity (i.e., pemetrexed, gemcitabine±bevacizumab, vinorelbine) as neo-adjuvant, adjuvant or palliative therapy. Patients with progressive disease on therapy with an EGFR-TKI (Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors) and scheduled to receive cisplatin-based chemotherapy will be eligible for the study.
* ECOG (Eastern Cooperative Oncology Group) Performance Status of 0-1.
* Body Mass Index ≥18.5.
* Written informed consent before study entry.
* If women of childbearing potential age: effective contraceptive measures must be used during all the planned course of chemotherapy and up to 30 days after last NEPA administration.
* Normal 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 and study questionnaires.

* Psychiatric or CNS (Central Nervous System) disorders interfering with ability to comply with study protocol.

Exclusion Criteria

* Symptomatic brain metastases.
* Patients scheduled to receive radiation therapy to the abdomen or pelvis within 1 week before day 1 or between day 1 and 5 following the first cycle of chemotherapy.
* Patients scheduled to receive concurrent chemo/radiotherapy for NSCLC.
* Treatment with investigational medications within 30 days before the study medication.
* Myocardial infarction within the last 6 months.
* Documented or known hypersensitivity to 5HT3RA (5-Hydroxytryptamine Receptor 3 Antagonists) or NK-1RA (Neurokinin-1 Receptor Antagonist) and excipients (see section 6.1 of Akynzeo SPC).
* Uncontrolled diabetes mellitus or active infection.
* Nausea and vomiting in the 24 hours before study treatment.
* Chronic use of systemic corticosteroids (except for topical and inhaled corticosteroids) or any other agent with anti-emetic potential. Patients receiving dexamethasone on the day before chemotherapy for prevention of the pemetrexed-induced skin rash will be eligible for the study.
* Patient's inability to take oral medication.
* Gastrointestinal obstruction or active peptic ulcer.
* Pregnancy or breast feeding.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Consorzio Oncotech

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Emilio Bria, MD

Role: STUDY_CHAIR

Fondazione Policlinico Universitario "A. Gemelli" IRCCS, UCSC - Rome (Italy)

Luigi Celio, MD

Role: STUDY_DIRECTOR

Fondazione IRCCS "Istituto Nazionale Tumori" - Milan (Italy)

Locations

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ASST Bergamo Ovest - Ospedale di Teviglio

Treviglio, BG, Italy

Site Status

Azienda ULSS 1 Dolomiti - Ospedale Santa Maria del Prato

Feltre, BL, Italy

Site Status

ASST Ovest Milanese - Ospedale di Legnano

Legnano, MI, Italy

Site Status

AOU San Luigi Gonzaga

Orbassano, TO, Italy

Site Status

A.O.U. Consorziale Policlinico di Bari

Bari, , Italy

Site Status

IRCCS Istituto Tumori "Giovanni Paolo II"

Bari, , Italy

Site Status

ASST Spedali Civili di Brescia

Brescia, , Italy

Site Status

Azienda Ospedaliera Cosenza

Cosenza, , Italy

Site Status

ASST Lecco - P.O. "A. Manzoni"

Lecco, , Italy

Site Status

A.O.U. Policlinico di Modena

Modena, , Italy

Site Status

Ospedale San Gerardo - ASST Monza

Monza, , Italy

Site Status

A.O.R.N. dei Colli - Ospedale Monaldi

Napoli, , Italy

Site Status

Casa di Cura di Alta Specialità Dip. Oncologico di III livello "La Maddalena"

Palermo, , Italy

Site Status

Ospedale S. Maria della Misericordia

Perugia, , Italy

Site Status

Ospedale di Piacenza

Piacenza, , Italy

Site Status

IRCCS Arcispedale S. Maria Nuova

Reggio Emilia, , Italy

Site Status

A.O. San Camillo Forlanini

Roma, , Italy

Site Status

A.O. San Giovanni - Addolorata

Roma, , Italy

Site Status

Fondazione Policlinico "A. Gemelli" - Università Cattolica Sacro Cuore

Roma, , Italy

Site Status

Istituto Nazionale Tumori "Regina Elena"

Roma, , Italy

Site Status

Policlinico Tor Vergata

Roma, , Italy

Site Status

Ospedale Civile SS. Annunziata

Sassari, , Italy

Site Status

Ospedale Umberto I - RAO SR

Syracuse, , Italy

Site Status

P.O. "San Giuseppe Moscati"

Taranto, , Italy

Site Status

Azienda ULSS 2 Marca Trevigiana - Ospedale di Treviso

Treviso, , Italy

Site Status

A.O.U.I. Verona - Policlinico "G.B. Rossi"

Verona, , Italy

Site Status

Countries

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Italy

References

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Celio L, Aapro M. Characteristics of nausea and its impact on health-related quality of life in cisplatin-treated patients receiving dexamethasone-sparing prophylaxis: an analysis of the LUNG-NEPA study. Support Care Cancer. 2024 Mar 4;32(3):204. doi: 10.1007/s00520-024-08406-5.

Reference Type DERIVED
PMID: 38433125 (View on PubMed)

Celio L, Bartsch R, Aapro M. Dexamethasone-sparing regimens with NEPA (netupitant/palonosetron) for the prevention of chemotherapy-induced nausea and vomiting in older patients (>65 years) fit for cisplatin: A sub-analysis from a phase 3 study. J Geriatr Oncol. 2023 Jul;14(6):101537. doi: 10.1016/j.jgo.2023.101537. Epub 2023 Jun 7.

Reference Type DERIVED
PMID: 37290207 (View on PubMed)

Celio L, Cortinovis D, Cogoni AA, Cavanna L, Martelli O, Carnio S, Collova E, Bertolini F, Petrelli F, Cassano A, Chiari R, Zanelli F, Pisconti S, Vittimberga I, Letizia A, Misino A, Gernone A, Bonizzoni E, Pilotto S, De Placido S, Bria E. Exploratory analysis of the effect of a dexamethasone-sparing regimen for prophylaxis of cisplatin-induced emesis on food intake (LUNG-NEPA study). Sci Rep. 2023 Jan 23;13(1):1257. doi: 10.1038/s41598-023-28464-9.

Reference Type DERIVED
PMID: 36690734 (View on PubMed)

Celio L, Cortinovis D, Cogoni AA, Cavanna L, Martelli O, Carnio S, Collova E, Bertolini F, Petrelli F, Cassano A, Chiari R, Zanelli F, Pisconti S, Vittimberga I, Letizia A, Misino A, Gernone A, Bonizzoni E, Pilotto S, De Placido S, Bria E. Evaluating the impact of chemotherapy-induced nausea and vomiting on daily functioning in patients receiving dexamethasone-sparing antiemetic regimens with NEPA (netupitant/palonosetron) in the cisplatin setting: results from a randomized phase 3 study. BMC Cancer. 2022 Aug 24;22(1):915. doi: 10.1186/s12885-022-10018-3.

Reference Type DERIVED
PMID: 35999527 (View on PubMed)

Other Identifiers

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LUNG-NEPA

Identifier Type: -

Identifier Source: org_study_id

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