Dexamethasone-sparing Approach Including NEPA Against Emesis Caused by Cisplatin
- Conditions
- Chemotherapy-induced Nausea and Vomiting
- Interventions
- Drug: Netupitant/Palonosetron
- Registration Number
- NCT04201769
- Lead Sponsor
- Consorzio Oncotech
- 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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 261
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A Netupitant/Palonosetron Oral Netupitant/Palonosetron (NEPA) and intravenous Dexamethasone (DEX) on Day 1 of chemotherapy. No further anti-emetic prophylaxis on days 2 thorough 4. Arm B Netupitant/Palonosetron 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. Arm C Netupitant/Palonosetron 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. Arm B Dexamethasone 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. Arm A Dexamethasone Oral Netupitant/Palonosetron (NEPA) and intravenous Dexamethasone (DEX) on Day 1 of chemotherapy. No further anti-emetic prophylaxis on days 2 thorough 4. Arm C Dexamethasone 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.
- Primary Outcome Measures
Name Time Method Complete Response (CR) During the overall phase (day 1 thorough 5) of the first cycle of cisplatin-based chemotherapy (each cycle is 7 or 21 days) 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.
- Secondary Outcome Measures
Name Time Method 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) No emetic episode and no use of rescue medication, during the acute and delayed phases
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) No emetic episode, no rescue medication, and no more than mild nausea. Severity of nausea will be self-reported by the patient using a verbal scale (none, mild, moderate, and severe).
Safety profile During all the safety study period (up to three weeks after the start of cisplatin-based chemotherapy) Safety profile according to NCI-CTCAE version 5.0
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) No emetic episode
Patient global satisfaction with anti-emetic therapy, On day 6 of the first cycle of cisplatin-based chemotherapy (each cycle is 7 or 21 days) Patient global satisfaction with antiemetic therapy, as measured by a Visual Analogue Scale (VAS) on day 6. Scale ranges are 0-10 (0 represents maximum dissatisfaction, 10 represents maximum satisfaction)
Cross-sectional baseline evaluation of weight loss (WL) During the Screening phase (up to 7 days before the first cycle of chemotherapy administration - each cycle is 7 or 21 days) Weight loss will be assessed through the BMI (Body Mass Index) adjusted weight loss grading system (WLGS).
WL as classified according to WLGS, a grading system using the combination of %WL and BMI categories. The analysis will be laid out in a 5x5 matrix representing five different %WL categories within each of the five different BMI categories (25 possible combinations of WL and BMI).
Percentage of WL will be defined as follows: \[(current weight in Kg - previous weight in Kg)/previous weight in Kg\] x 100. Previous patient weight (i.e., the usual weight) within the last 6 months (or "usual weight") will be also collected at baseline. BMI will be calculated as current weight/square of the body height (Kg/m2);Nutritional intake During the Screening phase (up to 7 days before the first cycle of chemotherapy administration - each cycle is 7 or 21 days) Nutritional intake will be assessed with an ad hoc question adapted from the Patient Generated-Subjective Global Assessment (PG-SGA) questionnaire.
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) No nausea. Severity of nausea will be self-reported by the patient using a verbal scale (none, mild, moderate, and severe).
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) Impact of nausea and vomiting on patient's quality of life as recorded by the Italian version of the FLIE (Functional Living Index-Emesis) questionnaire, according to subjective assessment by each patient on day 6.
The questionnaire consists of 18 questions: the first set of 9 questions refers to nausea and the second set of 9 questions refers to vomiting.
Each question uses a visual analogue scale. Scale ranges are 1-7 (in some questions 1 indicates no effect on patient's quality of life, in other questions 1 indicates a great deal of an effect on patient's quality of life).Cancer-related symptom self-assessment On day 1 of the first cycle of cisplatin-based chemotherapy (each cycle is 7 or 21 days) Cancer-related symptom self-assessment, as recorded by the Italian version of the ESAS (Edmonton Symptom Assessment Scale) questionnaire, according to subjective assessment by each patient on day 1 (before cisplatin-based chemotherapy initiation), will be performed.
The ESAS is a validated symptom inventory tool assessing the current intensity of 10 common symptoms in cancer patients, each with an 11-point numerical rating scale from 0 (no symptom) to 10 (worst intensity).Cancer-related symptom self-assessment association with WLGS and nutritional intake On day 1 of the first cycle of cisplatin-based chemotherapy (each cycle is 7 or 21 days) The association between Cancer-related symptom self-assessment and WLGS and nutritional intake will be examined using linear regression models.
Trial Locations
- Locations (26)
Ospedale Civile SS. Annunziata
🇮🇹Sassari, Italy
Istituto Nazionale Tumori "Regina Elena"
🇮🇹Roma, Italy
Ospedale Umberto I - RAO SR
🇮🇹Siracusa, Italy
AOU San Luigi Gonzaga
🇮🇹Orbassano, TO, Italy
Policlinico Tor Vergata
🇮🇹Roma, Italy
P.O. "San Giuseppe Moscati"
🇮🇹Taranto, Italy
Azienda ULSS 2 Marca Trevigiana - Ospedale di Treviso
🇮🇹Treviso, Italy
A.O.U.I. Verona - Policlinico "G.B. Rossi"
🇮🇹Verona, Italy
ASST Bergamo Ovest - Ospedale di Teviglio
🇮🇹Treviglio, BG, Italy
IRCCS Istituto Tumori "Giovanni Paolo II"
🇮🇹Bari, Italy
Azienda ULSS 1 Dolomiti - Ospedale Santa Maria del Prato
🇮🇹Feltre, BL, Italy
ASST Ovest Milanese - Ospedale di Legnano
🇮🇹Legnano, MI, Italy
ASST Lecco - P.O. "A. Manzoni"
🇮🇹Lecco, Italy
A.O.U. Policlinico di Modena
🇮🇹Modena, Italy
A.O.U. Consorziale Policlinico di Bari
🇮🇹Bari, Italy
A.O.R.N. dei Colli - Ospedale Monaldi
🇮🇹Napoli, Italy
Casa di Cura di Alta Specialità Dip. Oncologico di III livello "La Maddalena"
🇮🇹Palermo, Italy
Ospedale S. Maria della Misericordia
🇮🇹Perugia, Italy
IRCCS Arcispedale S. Maria Nuova
🇮🇹Reggio Emilia, Italy
A.O. San Camillo Forlanini
🇮🇹Roma, Italy
A.O. San Giovanni - Addolorata
🇮🇹Roma, Italy
ASST Spedali Civili di Brescia
🇮🇹Brescia, Italy
Azienda Ospedaliera Cosenza
🇮🇹Cosenza, Italy
Ospedale San Gerardo - ASST Monza
🇮🇹Monza, Italy
Ospedale di Piacenza
🇮🇹Piacenza, Italy
Fondazione Policlinico "A. Gemelli" - Università Cattolica Sacro Cuore
🇮🇹Roma, Italy