A Multicenter, Randomized, Double-blind, Double-dummy, Active-controlled, Parallel Group Phase 3b Study to Assess the Safety and to Describe the Efficacy of IV Fosnetupitant/Palonosetron (260 mg/0.25 mg) Combination (IV NEPA FDC) Compared to Oral Netupitant/Palonosetron (300 mg/0.5 mg) Combination (Akynzeo®) for the Prevention of Chemotherapy-induced Nausea and Vomiting in Initial and Repeated Cycles of Anthracycline-cyclophosphamide (AC) Chemotherapy in Women With Breast Cancer
Overview
- Phase
- Phase 3
- Intervention
- fosnetupitant/ palonosetron
- Conditions
- Chemotherapy-induced Nausea and Vomiting
- Sponsor
- Helsinn Healthcare SA
- Enrollment
- 404
- Locations
- 40
- Primary Endpoint
- Number of Participants With Treatment-emergent AEs at Cycle 1
- Status
- Completed
- Last Updated
- 5 years ago
Overview
Brief Summary
Multicenter, randomized, double-blind, double-dummy, parallel group, stratified study assessing the safety and describing the efficacy of a single dose of intravenous (IV) fosnetupitant/palonosetron (260 mg/0.25 mg) infusion [test] versus oral netupitant/palonosetron (300 mg/0.5 mg) combination [control]; each administered with oral dexamethasone prior to initial and repeated cycles of AC chemotherapy in female breast cancer patients.
Investigators
Eligibility Criteria
Inclusion Criteria
- •The following inclusion criteria must be checked prior to inclusion at Cycle 1:
- •Patient read, understood and signed the written informed consent before any study related activity, agreeing to participate in the study and to comply with study requirements.
- •Female patient of at least 8 years of age.
- •Histologically or cytologically confirmed breast cancer, including recurrent or metastatic.
- •Naïve to moderately or highly emetogenic antineoplastic agents.
- •Scheduled to receive at least 4 consecutive cycles of an AC combination regimen.
- •additional not emetogenic, minimally or low emetogenic antineoplastic agents are permitted at any time after start of AC combination on Day
- •additional highly or moderately emetogenic antineoplastic agents are only allowed on Day 1 after the start of AC combination, provided their administration is completed within 6 hours from the start of the AC combination administration.
- •ECOG Performance Status of 0 or
- •Patient shall be: a) of non-childbearing potential or b) of childbearing potential using reliable contraceptive measures and having a negative urine pregnancy test within 24 hours prior to dose of investigational product.
Exclusion Criteria
- •The following exclusion criteria must be checked prior to inclusion at Cycle 1:
- •Lactating patient.
- •Current use of illicit drugs or current evidence of alcohol abuse.
- •Scheduled to receive moderately or highly emetogenic antineoplastic agent in addition to the AC regimen, from 6 hours after the start of the AC chemotherapy on Day 1 and up to Day 1 of Cycle
- •Received or is scheduled to receive radiation therapy to the abdomen or the pelvis within 1 week prior to the start of AC chemotherapy administration on Day 1 or between Days 1 to 5, inclusive.
- •Any vomiting, retching, or nausea (grade 1 as defined by National Cancer Institute) within 24 hours prior to the start of AC chemotherapy administration on Day
- •Symptomatic primary or metastatic central nervous system (CNS) malignancy.
- •Active peptic ulcer disease, gastrointestinal obstruction, increased intracranial pressure, hypercalcemia, an active infection or any illness or medical conditions (other than malignancy) that, in the opinion of the Investigator, may confound the results of the study, represent another potential etiology for emesis and nausea (other than chemotherapy-induced nausea and vomiting \[CINV\]) or pose unwarranted risks in administering the study drugs to the patient.
- •Known hypersensitivity or contraindication to 5 hydroxytryptamine type 3 (5-HT3) receptor antagonists (e.g., palonosetron, ondansetron, granisetron, dolasetron, tropisetron, ramosetron), to dexamethasone, or to neurokinin-1 (NK1) receptor antagonists (e.g., aprepitant, rolapitant).
- •Known contraindication to the IV administration of 50 mL 5% glucose solution.
Arms & Interventions
Test group
intravenous fosnetupitant/ palonosetron (260 mg/0.25 mg) fixed-dose combination, administered as a 30-minute infusion of a 50 mL solution, on Day 1 of each cycle. Oral dexamethasone will be administered on Day 1 of each cycle (12 mg)
Intervention: fosnetupitant/ palonosetron
Test group
intravenous fosnetupitant/ palonosetron (260 mg/0.25 mg) fixed-dose combination, administered as a 30-minute infusion of a 50 mL solution, on Day 1 of each cycle. Oral dexamethasone will be administered on Day 1 of each cycle (12 mg)
Intervention: dexamethasone
Control group
oral netupitant/palonosetron (300 mg/0.50 mg) fixed-dose combination on Day 1 of each cycle. Oral dexamethasone will be administered on Day 1 of each cycle (12 mg)
Intervention: netupitant/palonosetron
Control group
oral netupitant/palonosetron (300 mg/0.50 mg) fixed-dose combination on Day 1 of each cycle. Oral dexamethasone will be administered on Day 1 of each cycle (12 mg)
Intervention: dexamethasone
Outcomes
Primary Outcomes
Number of Participants With Treatment-emergent AEs at Cycle 1
Time Frame: At the end of Cycle 1 (each cycle is 21 days)
Number of Participants With Treatment-emergent AEs All Cycles
Time Frame: At the end of Cycle 4 (each cycle is 21 days)
Number of Participants With Severe (i.e., CTCAE Grade ≥3) TEAEs Reported for ≥2% of Patients in Either Treatment Group and Overall Throughout the Study
Time Frame: At the end of Cycle 4 (each cycle is 21 days)
Number of Participants With Study-Drug-Related TEAEs Reported for ≥2% of Patients in Either Treatment Group Throughout the Study
Time Frame: At the end of Cycle 4 (each cycle is 21 days)
Secondary Outcomes
- Complete Response in Cycle 1 During the Acute Phase(24 hours after the start of AC chemotherapy administration)
- Complete Response in Cycle 1 During the Delayed Phase(120 hour after the start of AC chemotherapy administration)
- Complete Response in Cycle 1 During the Overall Phase(0-120 hours after the start of AC chemotherapy)
- Overall Percentage of Patients With NIDL Based on FLIE Scores for Cycles 1(cycle 1)