Clinical Trials List
Protocol NumberNETU-12-07
2013-08-22 - 2015-06-30
Phase III
Terminated7
A randomized, double-blind, double-dummy, parallel group, international multicenter study assessing the efficacy and safety of a netupitant-palonosetron Fixed Dose Combination (FDC) compared to an extemporary combination of granisetron and aprepitant on the prevention of highly emetogenic chemotherapy-induced nausea and vomiting in patients with cancer.
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Trial Applicant
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Sponsor
Helsinn Birex Pharmaceuticals Ltd
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Chien-Wei Su Division of Hematology & Oncology
- 林炯森 Division of Hematology & Oncology
- 林建鴻 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Jih-Hsiang Lee Division of Hematology & Oncology
- 陳怡君 Division of Hematology & Oncology
- Chia-Chi Lin Division of Hematology & Oncology
- HUAI-CHENG HUANG Division of Hematology & Oncology
- 林宗哲 Division of Hematology & Oncology
- 呂理駿 Division of Hematology & Oncology
- 張端瑩 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 曾思文 Division of Hematology & Oncology
- Ming-Hung Tsai Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Shang-Yin Wu Division of Hematology & Oncology
- Ya-Ping Chen Division of Hematology & Oncology
- Chia-Jui Yen Division of Hematology & Oncology
- Yu-Min Yeh Division of Hematology & Oncology
- Wen-Pin Su Division of Hematology & Oncology
- Wei-Pang Chung Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Kuan-Der Lee Division of Hematology & Oncology
- 黃慈恩 Division of Hematology & Oncology
- 官鋒澤 Division of Hematology & Oncology
- 陳秉聰 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Che-Hung Lin Division of Hematology & Oncology
- Li-Yuan Bai Division of Hematology & Oncology
- Ching Yun Hsieh Division of Hematology & Oncology
- Chang-Fang Chiu Division of Hematology & Oncology
- Ching-Chan Lin Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
828 Terminated
Audit
None
Co-Principal Investigator
- Chien-Wei Su Division of Hematology & Oncology
- 林炯森 Division of Hematology & Oncology
- 林建鴻 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Condition/Disease
nausea and vomiting
Objectives
Primary Objective:
To demonstrate the non-inferiority of netupitant-palonosetron fixed dose combination (NETU-PALO FDC) versus an extemporary combination of granisetron and aprepitant (Aprep-Granis) in the prevention of highly emetogenic chemotherapy (HEC) -induced nausea and vomiting.
Secondary Objective:
To describe the efficacy of NETU-PALO FDC versus Aprep-Granis by the evaluation of further secondary efficacy variables during the acute (0-24 hours), the delayed (25-120 hours) and overall (0-120 hours) phases.
To assess the safety and tolerability of NETU-PALO FDC in patients receiving HEC.
Test Drug
netupitant-palonosetron Fixed Dose Combination (FDC)
Active Ingredient
netupitant + palonosetron
Dosage Form
capsule/oral
Dosage
netupitant 300 mg / palonosetron 0.5 mg
Endpoints
Primary efficacy endpoint:
The primary efficacy endpoint is CR (defined as no emetic episodes, no rescue medication) within 120 hours after the start of the highly emetogenic chemotherapy administration.
Secondary efficacy endpoint:
1. CR for the 0-24 hours, 25-120 hours interval and for each 24-hour interval after the start of cisplatin-based HEC;
2. Absence of significant nausea (visual analogue scale [VAS] <25 mm); considering each 24-hour interval (starting from 0-24 hours from the start of cisplatin-based chemotherapy administration) as well as over 0-120 hours and 25-120 hours;
3. Absence of nausea (VAS <5 mm); considering each 24-hour interval (starting from 0-24 hours from the start of cisplatin-based chemotherapy administration) as well as over 0-120 hours and 25-120 hours;
4. Absence of emesis; considering each 24-hour interval (starting from 0-24 hours from the start of cisplatin-based chemotherapy administration) as well as over 0-120 hours and 25-120 hours;
5. Absence of rescue medication use; considering each 24-hour interval (starting from 0-24 hours from the start of cisplatin-based chemotherapy administration) as well as over 0-120 hours and 25-120 hours;
6. Severity of nausea (measured by means of a VAS) for each 24-hour interval;
The primary efficacy endpoint is CR (defined as no emetic episodes, no rescue medication) within 120 hours after the start of the highly emetogenic chemotherapy administration.
Secondary efficacy endpoint:
1. CR for the 0-24 hours, 25-120 hours interval and for each 24-hour interval after the start of cisplatin-based HEC;
2. Absence of significant nausea (visual analogue scale [VAS] <25 mm); considering each 24-hour interval (starting from 0-24 hours from the start of cisplatin-based chemotherapy administration) as well as over 0-120 hours and 25-120 hours;
3. Absence of nausea (VAS <5 mm); considering each 24-hour interval (starting from 0-24 hours from the start of cisplatin-based chemotherapy administration) as well as over 0-120 hours and 25-120 hours;
4. Absence of emesis; considering each 24-hour interval (starting from 0-24 hours from the start of cisplatin-based chemotherapy administration) as well as over 0-120 hours and 25-120 hours;
5. Absence of rescue medication use; considering each 24-hour interval (starting from 0-24 hours from the start of cisplatin-based chemotherapy administration) as well as over 0-120 hours and 25-120 hours;
6. Severity of nausea (measured by means of a VAS) for each 24-hour interval;
Inclution Criteria
For inclusion in the study, patients must fulfill all of the following criteria:
1. Provide written informed consent;
2. Male or female, aged 18 years or over;
3. Cytotoxicchemotherapynaïve;
4. Have a histologically or cytologically confirmed solid tumor malignancy;
5. Be scheduled to receive the first course of cisplatin-based chemotherapy regimen (≥ 50 mg/m2) that is to be administered over 1 to 4 hours on Day 1 (either alone or in combination with other chemotherapy agents);
6. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2;
7. Non-fertile patient or fertile patient (male or female) using reliable contraceptive measures1
8. Female patients of childbearing potential2 must have a negative urine pregnancy test3);
9. Able to read, understand, and follow the study procedures and able to complete patient diary independently.
1. Provide written informed consent;
2. Male or female, aged 18 years or over;
3. Cytotoxicchemotherapynaïve;
4. Have a histologically or cytologically confirmed solid tumor malignancy;
5. Be scheduled to receive the first course of cisplatin-based chemotherapy regimen (≥ 50 mg/m2) that is to be administered over 1 to 4 hours on Day 1 (either alone or in combination with other chemotherapy agents);
6. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2;
7. Non-fertile patient or fertile patient (male or female) using reliable contraceptive measures1
8. Female patients of childbearing potential2 must have a negative urine pregnancy test3);
9. Able to read, understand, and follow the study procedures and able to complete patient diary independently.
Exclusion Criteria
Any of the following is regarded as a criterion for exclusion from the study:
1. Current use of illicit drugs or current evidence of alcohol abuse;
2. Scheduled to receive moderately emetogenic chemotherapy (MEC) or HEC from Day 2 to Day 5 following cisplatin-based chemotherapy administration;
3. Scheduled to receive bone marrow or stem cell transplant;
4. Moderately- or highly-emetogenic radiotherapy within 1 week prior to Day 1 or scheduled for study Days 1 to 5;
5. Any drug with potential antiemetic efficacy taken within 24 hours prior to Day 1;
6. Systemic corticosteroid therapy (including but not limited to dexamethasone, hydrocortisone, methylprednisolone, or prednisolone) other than that required by the protocol given within 72 hours prior to Day 1 (Note: topical or inhaled steroids are permitted);
7. Neurokinin (NK)1 receptor antagonists or any investigational drugs taken within 4 weeks prior to Day 1;
8. Hematologic and metabolic status inadequate for receiving a cisplatin- based HEC regimen, including any of the following criteria:
a) Absolute neutrophil count <1500/mm3 and white blood cell (WBC) count <3000/mm3
b) Platelet count <100,000/mm3
c) Bilirubin >1.5 x upper limit of normal (ULN)
d) Liver enzymes:
In patients without known liver metastases:
• aspartate aminotransferase (AST) ≥ 2.5 x ULN
• alanine aminotransferase (ALT) ≥ 2.5 x ULN In patients with known liver metastases:
• AST ≥ 5.0 x ULN
• ALT ≥ 5.0 x ULN
e) Serum creatinine ≥ 1.5 mg/dL (standard units: ≥132.6 μ MOL/L)
f) Creatinine clearance ≤ 50 mL/min;
9. Active infection (e.g. pneumonia) or any uncontrolled disease (e.g. diabetic ketoacidosis or gastrointestinal obstruction) that, in the opinion of the Investigator, may confound the results of the study or pose unwarranted risk in administering the study drug treatments;
10. History or predisposition to cardiac conduction abnormalities (like Torsade de Point, long QT syndrome or others), except for incomplete right bundle branch block;
11. Serious cardiovascular diseases, including acute myocardial infarction, unstable angina pectoris, significant valvular or pericardial disease, history of ventricular tachycardia, symptomatic chronic heart failure (New York Heart Association [NYHA] class III-IV), and severe uncontrolled arterial hypertension;
12. History of any illness that, in the opinion of the Investigator, may confound the results of the study or pose unwarranted risk in administering the study treatments;
13. Any vomiting, retching, or more than mild nausea within 24 hours prior to Day 1;
14. Ongoing or recent history of somatic disease causing nausea or vomiting;
15. Symptomatic primary or metastatic central nervous system malignancy;
16. Chronic use of any CYP3A4 substrates or inhibitors (e.g . terfenadine, cisapride, astemizole, clarithromycine, ketoconazole or itraconazole) or their intake within 1 week prior to Day 1;
17. Chronic use of any CYP3A4 inducers (e.g . barbiturates, rifampicin, rifabutin, phenytoin or carbamazepine) or their intake within 4 weeks prior to Day 1;
18. Concurrent medical condition that would delay dexamethasone administration by 4 days (e.g. systemic fungal infection or uncontrolled diabetes);
19. Known contraindications to NK1 receptor antagonists, 5-HT3 receptor antagonists or dexamethasone;
20. Enrolment in a previous study with netupitant (either alone or in combination with palonosetron).
1. Current use of illicit drugs or current evidence of alcohol abuse;
2. Scheduled to receive moderately emetogenic chemotherapy (MEC) or HEC from Day 2 to Day 5 following cisplatin-based chemotherapy administration;
3. Scheduled to receive bone marrow or stem cell transplant;
4. Moderately- or highly-emetogenic radiotherapy within 1 week prior to Day 1 or scheduled for study Days 1 to 5;
5. Any drug with potential antiemetic efficacy taken within 24 hours prior to Day 1;
6. Systemic corticosteroid therapy (including but not limited to dexamethasone, hydrocortisone, methylprednisolone, or prednisolone) other than that required by the protocol given within 72 hours prior to Day 1 (Note: topical or inhaled steroids are permitted);
7. Neurokinin (NK)1 receptor antagonists or any investigational drugs taken within 4 weeks prior to Day 1;
8. Hematologic and metabolic status inadequate for receiving a cisplatin- based HEC regimen, including any of the following criteria:
a) Absolute neutrophil count <1500/mm3 and white blood cell (WBC) count <3000/mm3
b) Platelet count <100,000/mm3
c) Bilirubin >1.5 x upper limit of normal (ULN)
d) Liver enzymes:
In patients without known liver metastases:
• aspartate aminotransferase (AST) ≥ 2.5 x ULN
• alanine aminotransferase (ALT) ≥ 2.5 x ULN In patients with known liver metastases:
• AST ≥ 5.0 x ULN
• ALT ≥ 5.0 x ULN
e) Serum creatinine ≥ 1.5 mg/dL (standard units: ≥132.6 μ MOL/L)
f) Creatinine clearance ≤ 50 mL/min;
9. Active infection (e.g. pneumonia) or any uncontrolled disease (e.g. diabetic ketoacidosis or gastrointestinal obstruction) that, in the opinion of the Investigator, may confound the results of the study or pose unwarranted risk in administering the study drug treatments;
10. History or predisposition to cardiac conduction abnormalities (like Torsade de Point, long QT syndrome or others), except for incomplete right bundle branch block;
11. Serious cardiovascular diseases, including acute myocardial infarction, unstable angina pectoris, significant valvular or pericardial disease, history of ventricular tachycardia, symptomatic chronic heart failure (New York Heart Association [NYHA] class III-IV), and severe uncontrolled arterial hypertension;
12. History of any illness that, in the opinion of the Investigator, may confound the results of the study or pose unwarranted risk in administering the study treatments;
13. Any vomiting, retching, or more than mild nausea within 24 hours prior to Day 1;
14. Ongoing or recent history of somatic disease causing nausea or vomiting;
15. Symptomatic primary or metastatic central nervous system malignancy;
16. Chronic use of any CYP3A4 substrates or inhibitors (e.g . terfenadine, cisapride, astemizole, clarithromycine, ketoconazole or itraconazole) or their intake within 1 week prior to Day 1;
17. Chronic use of any CYP3A4 inducers (e.g . barbiturates, rifampicin, rifabutin, phenytoin or carbamazepine) or their intake within 4 weeks prior to Day 1;
18. Concurrent medical condition that would delay dexamethasone administration by 4 days (e.g. systemic fungal infection or uncontrolled diabetes);
19. Known contraindications to NK1 receptor antagonists, 5-HT3 receptor antagonists or dexamethasone;
20. Enrolment in a previous study with netupitant (either alone or in combination with palonosetron).
The Estimated Number of Participants
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Taiwan
109 participants
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Global
832 participants
