Dexamethasone-sparing Approach Including NEPA Against Emesis Caused by Cisplatin

NCT04201769 | Unknown Phase 3

• 1 other identifier: LUNG-NEPA
• Study Type: interventional
• Target: 261
• Locations: 1 country
• Sites: 26

Brief Summary

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

Conditions

Chemotherapy-induced Nausea and Vomiting

Keywords

nausea; vomiting; lung cancer; DEX-Sparing

Outcome Measures

Primary Outcomes (1)

• Complete Response (CR)

  The proportion of patients achieving a complete response, defined as no emetic episode and no use of rescue medication, during the overall study period (day 1 thorough 5) of the first cycle of chemotherapy.

  During the overall phase (day 1 thorough 5) of the first cycle of cisplatin-based chemotherapy (each cycle is 7 or 21 days)

Secondary Outcomes (11)

• CR (acute and delayed).

  During the acute (within 24 hours post-chemotherapy) and delayed (days 2 thorough 5) phases of the first cycle of cisplatin-based chemotherapy (each cycle is 7 or 21 days)

• Complete control

  During the acute (within 24 hours post-chemotherapy), delayed (days 2 thorough 5) and overall (days 1 thorough 5) phases of the first cycle of cisplatin-based chemotherapy (each cycle is 7 or 21 days)

• Proportion of patients with no emetic episode

  During the acute (within 24 hours post-chemotherapy), delayed (days 2 thorough 5) and overall (days 1 thorough 5) phases of the first cycle of cisplatin-based chemotherapy (each cycle is 7 or 21 days)

• Proportion of patients with no nausea

  During the acute (within 24 hours post-chemotherapy), delayed (days 2 thorough 5) and overall (days 1 thorough 5) phases of the first cycle of cisplatin-based chemotherapy (each cycle is 7 or 21 days)

• Impact of nausea and vomiting on patient's quality of life

  On day 6 of the first cycle of cisplatin-based chemotherapy (each cycle is 7 or 21 days)

Study Arms (3)

Arm A

EXPERIMENTAL

Oral Netupitant/Palonosetron (NEPA) and intravenous Dexamethasone (DEX) on Day 1 of chemotherapy. No further anti-emetic prophylaxis on days 2 thorough 4.

Drug: Netupitant/Palonosetron; Drug: Dexamethasone

Arm B

EXPERIMENTAL

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.

Drug: Netupitant/Palonosetron; Drug: Dexamethasone

Arm C

ACTIVE COMPARATOR

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.

Drug: Netupitant/Palonosetron; Drug: Dexamethasone

Interventions

Netupitant/Palonosetron DRUG

NEPA is adiministered 60 minutes before chemotherapy, on day 1

Also known as: Netupitant/Palonosetron 300-0.5 milligrams Oral Capsule [AKYNZEO]

Arm A; Arm B; Arm C

Dexamethasone 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 A; Arm B; Arm C

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Consorzio Oncotech: lead

Study Sites (26)

ASST Bergamo Ovest - Ospedale di Teviglio

Treviglio, BG, Italy

Location

Azienda ULSS 1 Dolomiti - Ospedale Santa Maria del Prato

Feltre, BL, Italy

Location

ASST Ovest Milanese - Ospedale di Legnano

Legnano, MI, Italy

Location

AOU San Luigi Gonzaga

Orbassano, TO, Italy

Location

A.O.U. Consorziale Policlinico di Bari

Bari, Italy

Location

IRCCS Istituto Tumori "Giovanni Paolo II"

Bari, Italy

Location

ASST Spedali Civili di Brescia

Brescia, Italy

Location

Azienda Ospedaliera Cosenza

Cosenza, Italy

Location

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

Lecco, Italy

Location

A.O.U. Policlinico di Modena

Modena, Italy

Location

Ospedale San Gerardo - ASST Monza

Monza, Italy

Location

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

Napoli, Italy

Location

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

Palermo, Italy

Location

Ospedale S. Maria della Misericordia

Perugia, Italy

Location

Ospedale di Piacenza

Piacenza, Italy

Location

IRCCS Arcispedale S. Maria Nuova

Reggio Emilia, Italy

Location

A.O. San Camillo Forlanini

Roma, Italy

Location

A.O. San Giovanni - Addolorata

Roma, Italy

Location

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

Roma, Italy

Location

Istituto Nazionale Tumori "Regina Elena"

Roma, Italy

Location

Policlinico Tor Vergata

Roma, Italy

Location

Ospedale Civile SS. Annunziata

Sassari, Italy

Location

Ospedale Umberto I - RAO SR

Syracuse, Italy

Location

P.O. "San Giuseppe Moscati"

Taranto, Italy

Location

Azienda ULSS 2 Marca Trevigiana - Ospedale di Treviso

Treviso, Italy

Location

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

Verona, Italy

Location

Related Publications (4)

• 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.

  PMID: 38433125 DERIVED

• 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.

  PMID: 37290207 DERIVED

• 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.

  PMID: 36690734 DERIVED

• 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.

  PMID: 35999527 DERIVED

MeSH Terms

Conditions

Vomiting; Nausea; Lung Neoplasms

Interventions

netupitant, palosentron drug combination; netupitant; Dexamethasone

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Emilio Bria, MD

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

  STUDY CHAIR

• Luigi Celio, MD

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

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase III, multicenter, randomized, open-label, parallel-group, active-comparator, three-arm, non-inferiority study

Study Record Dates

• First Submitted: December 11, 2019
• First Posted: December 17, 2019
• Study Start: November 25, 2016
• Primary Completion: April 1, 2020
• Study Completion: April 1, 2020
• Last Updated: April 3, 2020

Record last verified: 2020-04

Locations

IT (26)