Back to resultsDexamethasone-sparing Approach Including NEPA Against Emesis Caused by Cisplatin (LUNG-NEPA)
Primary Purpose
Chemotherapy-induced Nausea and Vomiting
Status
Unknown status
Phase
Phase 3
Locations
Italy
Study Type
Interventional
Intervention
Netupitant/Palonosetron
Dexamethasone
Sponsored by
About this trial
This is an interventional supportive care trial for Chemotherapy-induced Nausea and Vomiting focused on measuring nausea, vomiting, lung cancer, DEX-Sparing
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.
Sites / Locations
- ASST Bergamo Ovest - Ospedale di Teviglio
- Azienda ULSS 1 Dolomiti - Ospedale Santa Maria del Prato
- ASST Ovest Milanese - Ospedale di Legnano
- AOU San Luigi Gonzaga
- A.O.U. Consorziale Policlinico di Bari
- IRCCS Istituto Tumori "Giovanni Paolo II"
- ASST Spedali Civili di Brescia
- Azienda Ospedaliera Cosenza
- ASST Lecco - P.O. "A. Manzoni"
- A.O.U. Policlinico di Modena
- Ospedale San Gerardo - ASST Monza
- A.O.R.N. dei Colli - Ospedale Monaldi
- Casa di Cura di Alta Specialità Dip. Oncologico di III livello "La Maddalena"
- Ospedale S. Maria della Misericordia
- Ospedale di Piacenza
- IRCCS Arcispedale S. Maria Nuova
- A.O. San Camillo Forlanini
- A.O. San Giovanni - Addolorata
- Fondazione Policlinico "A. Gemelli" - Università Cattolica Sacro Cuore
- Istituto Nazionale Tumori "Regina Elena"
- Policlinico Tor Vergata
- Ospedale Civile SS. Annunziata
- Ospedale Umberto I - RAO SR
- P.O. "San Giuseppe Moscati"
- Azienda ULSS 2 Marca Trevigiana - Ospedale di Treviso
- A.O.U.I. Verona - Policlinico "G.B. Rossi"
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Active Comparator
Arm Label
Arm A
Arm B
Arm C
Arm Description
Oral Netupitant/Palonosetron (NEPA) and intravenous Dexamethasone (DEX) on Day 1 of chemotherapy. No further anti-emetic prophylaxis on days 2 thorough 4.
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.
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
CR (acute and delayed).
No emetic episode and no use of rescue medication, during the acute and delayed phases
Complete control
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).
Proportion of patients with no emetic episode
No emetic episode
Proportion of patients with no nausea
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
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).
Patient global satisfaction with anti-emetic therapy,
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)
Safety profile
Safety profile according to NCI-CTCAE version 5.0
Cross-sectional baseline evaluation of weight loss (WL)
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
Nutritional intake will be assessed with an ad hoc question adapted from the Patient Generated-Subjective Global Assessment (PG-SGA) questionnaire.
Cancer-related symptom self-assessment
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
The association between Cancer-related symptom self-assessment and WLGS and nutritional intake will be examined using linear regression models.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04201769
Brief Title
Dexamethasone-sparing Approach Including NEPA Against Emesis Caused by Cisplatin
Acronym
LUNG-NEPA
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
2. Study Status
Record Verification Date
April 2020
Overall Recruitment Status
Unknown status
Study Start Date
November 25, 2016 (Actual)
Primary Completion Date
April 2020 (Anticipated)
Study Completion Date
April 2020 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Consorzio Oncotech
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chemotherapy-induced Nausea and Vomiting
Keywords
nausea, vomiting, lung cancer, DEX-Sparing
7. Study Design
Primary Purpose
Supportive Care
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Phase III, multicenter, randomized, open-label, parallel-group, active-comparator, three-arm, non-inferiority study
Masking
None (Open Label)
Allocation
Randomized
Enrollment
261 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm A
Arm Type
Experimental
Arm Description
Oral Netupitant/Palonosetron (NEPA) and intravenous Dexamethasone (DEX) on Day 1 of chemotherapy.
No further anti-emetic prophylaxis on days 2 thorough 4.
Arm Title
Arm B
Arm Type
Experimental
Arm Description
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 Title
Arm C
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Netupitant/Palonosetron
Other Intervention Name(s)
Netupitant/Palonosetron 300-0.5 milligrams Oral Capsule [AKYNZEO]
Intervention Description
NEPA is adiministered 60 minutes before chemotherapy, on day 1
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Intervention Description
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
Primary Outcome Measure Information:
Title
Complete Response (CR)
Description
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.
Time Frame
During the overall phase (day 1 thorough 5) of the first cycle of cisplatin-based chemotherapy (each cycle is 7 or 21 days)
Secondary Outcome Measure Information:
Title
CR (acute and delayed).
Description
No emetic episode and no use of rescue medication, during the acute and delayed phases
Time Frame
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)
Title
Complete control
Description
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).
Time Frame
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)
Title
Proportion of patients with no emetic episode
Description
No emetic episode
Time Frame
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)
Title
Proportion of patients with no nausea
Description
No nausea. Severity of nausea will be self-reported by the patient using a verbal scale (none, mild, moderate, and severe).
Time Frame
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)
Title
Impact of nausea and vomiting on patient's quality of life
Description
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).
Time Frame
On day 6 of the first cycle of cisplatin-based chemotherapy (each cycle is 7 or 21 days)
Title
Patient global satisfaction with anti-emetic therapy,
Description
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)
Time Frame
On day 6 of the first cycle of cisplatin-based chemotherapy (each cycle is 7 or 21 days)
Title
Safety profile
Description
Safety profile according to NCI-CTCAE version 5.0
Time Frame
During all the safety study period (up to three weeks after the start of cisplatin-based chemotherapy)
Title
Cross-sectional baseline evaluation of weight loss (WL)
Description
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);
Time Frame
During the Screening phase (up to 7 days before the first cycle of chemotherapy administration - each cycle is 7 or 21 days)
Title
Nutritional intake
Description
Nutritional intake will be assessed with an ad hoc question adapted from the Patient Generated-Subjective Global Assessment (PG-SGA) questionnaire.
Time Frame
During the Screening phase (up to 7 days before the first cycle of chemotherapy administration - each cycle is 7 or 21 days)
Title
Cancer-related symptom self-assessment
Description
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).
Time Frame
On day 1 of the first cycle of cisplatin-based chemotherapy (each cycle is 7 or 21 days)
Title
Cancer-related symptom self-assessment association with WLGS and nutritional intake
Description
The association between Cancer-related symptom self-assessment and WLGS and nutritional intake will be examined using linear regression models.
Time Frame
On day 1 of the first cycle of cisplatin-based chemotherapy (each cycle is 7 or 21 days)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Emilio Bria, MD
Organizational Affiliation
Fondazione Policlinico Universitario "A. Gemelli" IRCCS, UCSC - Rome (Italy)
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Luigi Celio, MD
Organizational Affiliation
Fondazione IRCCS "Istituto Nazionale Tumori" - Milan (Italy)
Official's Role
Study Director
Facility Information:
Facility Name
ASST Bergamo Ovest - Ospedale di Teviglio
City
Treviglio
State/Province
BG
Country
Italy
Facility Name
Azienda ULSS 1 Dolomiti - Ospedale Santa Maria del Prato
City
Feltre
State/Province
BL
Country
Italy
Facility Name
ASST Ovest Milanese - Ospedale di Legnano
City
Legnano
State/Province
MI
Country
Italy
Facility Name
AOU San Luigi Gonzaga
City
Orbassano
State/Province
TO
Country
Italy
Facility Name
A.O.U. Consorziale Policlinico di Bari
City
Bari
Country
Italy
Facility Name
IRCCS Istituto Tumori "Giovanni Paolo II"
City
Bari
Country
Italy
Facility Name
ASST Spedali Civili di Brescia
City
Brescia
Country
Italy
Facility Name
Azienda Ospedaliera Cosenza
City
Cosenza
Country
Italy
Facility Name
ASST Lecco - P.O. "A. Manzoni"
City
Lecco
Country
Italy
Facility Name
A.O.U. Policlinico di Modena
City
Modena
Country
Italy
Facility Name
Ospedale San Gerardo - ASST Monza
City
Monza
Country
Italy
Facility Name
A.O.R.N. dei Colli - Ospedale Monaldi
City
Napoli
Country
Italy
Facility Name
Casa di Cura di Alta Specialità Dip. Oncologico di III livello "La Maddalena"
City
Palermo
Country
Italy
Facility Name
Ospedale S. Maria della Misericordia
City
Perugia
Country
Italy
Facility Name
Ospedale di Piacenza
City
Piacenza
Country
Italy
Facility Name
IRCCS Arcispedale S. Maria Nuova
City
Reggio Emilia
Country
Italy
Facility Name
A.O. San Camillo Forlanini
City
Roma
Country
Italy
Facility Name
A.O. San Giovanni - Addolorata
City
Roma
Country
Italy
Facility Name
Fondazione Policlinico "A. Gemelli" - Università Cattolica Sacro Cuore
City
Roma
Country
Italy
Facility Name
Istituto Nazionale Tumori "Regina Elena"
City
Roma
Country
Italy
Facility Name
Policlinico Tor Vergata
City
Roma
Country
Italy
Facility Name
Ospedale Civile SS. Annunziata
City
Sassari
Country
Italy
Facility Name
Ospedale Umberto I - RAO SR
City
Siracusa
Country
Italy
Facility Name
P.O. "San Giuseppe Moscati"
City
Taranto
Country
Italy
Facility Name
Azienda ULSS 2 Marca Trevigiana - Ospedale di Treviso
City
Treviso
Country
Italy
Facility Name
A.O.U.I. Verona - Policlinico "G.B. Rossi"
City
Verona
Country
Italy
12. IPD Sharing Statement
Citations:
PubMed Identifier
35999527
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.
Results Reference
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Dexamethasone-sparing Approach Including NEPA Against Emesis Caused by Cisplatin
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