Clinical trial NCT04201769: Dexamethasone-sparing Approach Including NEPA Against Emesis Caused by Cisplatin
Official title: A Standard Regimen of Dexamethasone in Comparison to Two Dex-sparing Regimens in Addition to NEPA in Preventing CINV in naïve NSCLC Patients to be Treated With Cisplatin Based Chemotherapy: a Three-arm, Open-label, Randomized Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Chemotherapy-induced Nausea and Vomiting
Keywords: nausea
vomiting
lung cancer
DEX-Sparing
Lead sponsor: Consorzio Oncotech
Sponsor class: OTHER
First posted: 2019-12-17
Enrollment: 261
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Phase III, multicenter, randomized, open-label, parallel-group, active-comparator, three-arm, non-inferiority study
Primary purpose: SUPPORTIVE_CARE

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

Detailed description: 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.

Eligibility criteria: 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.

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.
* 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 at least 5 years (see also inclusion criteria if prior chemotherapy treatment).
* Psychiatric or CNS (Central Nervous System) disorders interfering with ability to comply with study protocol.

Primary outcomes:
measure: Complete Response (CR)
timeFrame: 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:
measure: CR (acute and delayed).
timeFrame: 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)
measure: Complete control
timeFrame: 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)
measure: Proportion of patients with no emetic episode
timeFrame: 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)
measure: Proportion of patients with no nausea
timeFrame: 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)
measure: Impact of nausea and vomiting on patient's quality of life
timeFrame: On day 6 of the first cycle of cisplatin-based chemotherapy (each cycle is 7 or 21 days)
measure: Patient global satisfaction with anti-emetic therapy,
timeFrame: On day 6 of the first cycle of cisplatin-based chemotherapy (each cycle is 7 or 21 days)
measure: Safety profile
timeFrame: During all the safety study period (up to three weeks after the start of cisplatin-based chemotherapy)
measure: Cross-sectional baseline evaluation of weight loss (WL)
timeFrame: During the Screening phase (up to 7 days before the first cycle of chemotherapy administration - each cycle is 7 or 21 days)
measure: Nutritional intake
timeFrame: During the Screening phase (up to 7 days before the first cycle of chemotherapy administration - each cycle is 7 or 21 days)
measure: Cancer-related symptom self-assessment
timeFrame: On day 1 of the first cycle of cisplatin-based chemotherapy (each cycle is 7 or 21 days)
measure: Cancer-related symptom self-assessment association with WLGS and nutritional intake
timeFrame: On day 1 of the first cycle of cisplatin-based chemotherapy (each cycle is 7 or 21 days)
Other outcomes:
Locations:
city: Treviglio
country: Italy
facility: ASST Bergamo Ovest - Ospedale di Teviglio
state: BG
city: Feltre
country: Italy
facility: Azienda ULSS 1 Dolomiti - Ospedale Santa Maria del Prato
state: BL
city: Legnano
country: Italy
facility: ASST Ovest Milanese - Ospedale di Legnano
state: MI
city: Orbassano
country: Italy
facility: AOU San Luigi Gonzaga
state: TO
city: Bari
country: Italy
facility: A.O.U. Consorziale Policlinico di Bari
city: Bari
country: Italy
facility: IRCCS Istituto Tumori "Giovanni Paolo II"
city: Brescia
country: Italy
facility: ASST Spedali Civili di Brescia
city: Cosenza
country: Italy
facility: Azienda Ospedaliera Cosenza
city: Lecco
country: Italy
facility: ASST Lecco - P.O. "A. Manzoni"
city: Modena
country: Italy
facility: A.O.U. Policlinico di Modena
city: Monza
country: Italy
facility: Ospedale San Gerardo - ASST Monza
city: Napoli
country: Italy
facility: A.O.R.N. dei Colli - Ospedale Monaldi
city: Palermo
country: Italy
facility: Casa di Cura di Alta Specialità Dip. Oncologico di III livello "La Maddalena"
city: Perugia
country: Italy
facility: Ospedale S. Maria della Misericordia
city: Piacenza
country: Italy
facility: Ospedale di Piacenza
city: Reggio Emilia
country: Italy
facility: IRCCS Arcispedale S. Maria Nuova
city: Roma
country: Italy
facility: A.O. San Camillo Forlanini
city: Roma
country: Italy
facility: A.O. San Giovanni - Addolorata
city: Roma
country: Italy
facility: Fondazione Policlinico "A. Gemelli" - Università Cattolica Sacro Cuore
city: Roma
country: Italy
facility: Istituto Nazionale Tumori "Regina Elena"
city: Roma
country: Italy
facility: Policlinico Tor Vergata
city: Sassari
country: Italy
facility: Ospedale Civile SS. Annunziata
city: Siracusa
country: Italy
facility: Ospedale Umberto I - RAO SR
city: Taranto
country: Italy
facility: P.O. "San Giuseppe Moscati"
city: Treviso
country: Italy
facility: Azienda ULSS 2 Marca Trevigiana - Ospedale di Treviso
city: Verona
country: Italy
facility: A.O.U.I. Verona - Policlinico "G.B. Rossi"
Study officials:
affiliation: Fondazione Policlinico Universitario "A. Gemelli" IRCCS, UCSC - Rome (Italy)
name: Emilio Bria, MD
role: STUDY_CHAIR
affiliation: Fondazione IRCCS "Istituto Nazionale Tumori" - Milan (Italy)
name: Luigi Celio, MD
role: STUDY_DIRECTOR
References:
citation: 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.