Trial Outcomes & Findings for A Study to Assess the Safety and the Efficacy of IV Fosnetupitant/Palonosetron (260 mg/0.25 mg) Combination Compared to Oral Netupitant/Palonosetron (300 mg/0.5 mg) Combination for the Prevention of CINV in AC Chemotherapy in Women With Breast Cancer (NCT NCT03403712)
NCT ID: NCT03403712
Last Updated: 2020-06-01
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
404 participants
Primary outcome timeframe
At the end of Cycle 1 (each cycle is 21 days)
Results posted on
2020-06-01
Participant Flow
202 patients were randomized to IV NEPA and 202 patients were randomized to Oral NEPA. Two randomized patients (Patient IDs 211003 and 213001) in the IV NEPA group did not receive any active study drug or AC chemotherapy.
Participant milestones
| Measure |
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)
fosnetupitant/ palonosetron: intravenous fosnetupitant/ palonosetron (260 mg/0.25 mg) fixed-dose combination
dexamethasone: Oral dexamethasone (12 mg)
|
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)
netupitant/palonosetron: oral netupitant/palonosetron (300 mg/0.50 mg) fixed-dose combination
dexamethasone: Oral dexamethasone (12 mg)
|
|---|---|---|
|
Overall Study
STARTED
|
200
|
202
|
|
Overall Study
COMPLETED
|
95
|
102
|
|
Overall Study
NOT COMPLETED
|
105
|
100
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Study to Assess the Safety and the Efficacy of IV Fosnetupitant/Palonosetron (260 mg/0.25 mg) Combination Compared to Oral Netupitant/Palonosetron (300 mg/0.5 mg) Combination for the Prevention of CINV in AC Chemotherapy in Women With Breast Cancer
Baseline characteristics by cohort
| Measure |
Test Group
n=200 Participants
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)
fosnetupitant/ palonosetron: intravenous fosnetupitant/ palonosetron (260 mg/0.25 mg) fixed-dose combination
dexamethasone: Oral dexamethasone (12 mg)
|
Control Group
n=202 Participants
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)
netupitant/palonosetron: oral netupitant/palonosetron (300 mg/0.50 mg) fixed-dose combination
dexamethasone: Oral dexamethasone (12 mg)
|
Total
n=402 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
55.6 years
STANDARD_DEVIATION 9.94 • n=39 Participants
|
55.2 years
STANDARD_DEVIATION 9.73 • n=41 Participants
|
55.4 years
STANDARD_DEVIATION 9.82 • n=35 Participants
|
|
Age, Customized
<55 years
|
89 Participants
n=39 Participants
|
91 Participants
n=41 Participants
|
180 Participants
n=35 Participants
|
|
Age, Customized
>55 years
|
111 Participants
n=39 Participants
|
111 Participants
n=41 Participants
|
222 Participants
n=35 Participants
|
|
Sex: Female, Male
Female
|
200 Participants
n=39 Participants
|
202 Participants
n=41 Participants
|
402 Participants
n=35 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
7 Participants
n=39 Participants
|
8 Participants
n=41 Participants
|
15 Participants
n=35 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
192 Participants
n=39 Participants
|
189 Participants
n=41 Participants
|
381 Participants
n=35 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=39 Participants
|
5 Participants
n=41 Participants
|
6 Participants
n=35 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
1 Participants
n=35 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=39 Participants
|
1 Participants
n=41 Participants
|
2 Participants
n=35 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
1 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
1 Participants
n=35 Participants
|
|
Race (NIH/OMB)
Black or African American
|
4 Participants
n=39 Participants
|
9 Participants
n=41 Participants
|
13 Participants
n=35 Participants
|
|
Race (NIH/OMB)
White
|
189 Participants
n=39 Participants
|
186 Participants
n=41 Participants
|
375 Participants
n=35 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=39 Participants
|
1 Participants
n=41 Participants
|
1 Participants
n=35 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
4 Participants
n=39 Participants
|
5 Participants
n=41 Participants
|
9 Participants
n=35 Participants
|
|
Region of Enrollment
United States
|
41 participants
n=39 Participants
|
41 participants
n=41 Participants
|
82 participants
n=35 Participants
|
|
Region of Enrollment
Georgia
|
27 participants
n=39 Participants
|
33 participants
n=41 Participants
|
60 participants
n=35 Participants
|
|
Region of Enrollment
Russia
|
89 participants
n=39 Participants
|
92 participants
n=41 Participants
|
181 participants
n=35 Participants
|
|
Region of Enrollment
Ukraine
|
43 participants
n=39 Participants
|
36 participants
n=41 Participants
|
79 participants
n=35 Participants
|
|
Fertility Status
of childbearing potential
|
59 Participants
n=39 Participants
|
52 Participants
n=41 Participants
|
111 Participants
n=35 Participants
|
|
Fertility Status
post menopausal
|
120 Participants
n=39 Participants
|
128 Participants
n=41 Participants
|
248 Participants
n=35 Participants
|
|
Fertility Status
surgically sterile
|
21 Participants
n=39 Participants
|
22 Participants
n=41 Participants
|
43 Participants
n=35 Participants
|
PRIMARY outcome
Timeframe: At the end of Cycle 1 (each cycle is 21 days)Outcome measures
| Measure |
Test Group
n=200 Participants
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)
fosnetupitant/ palonosetron: intravenous fosnetupitant/ palonosetron (260 mg/0.25 mg) fixed-dose combination
dexamethasone: Oral dexamethasone (12 mg)
|
Control Group
n=202 Participants
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)
netupitant/palonosetron: oral netupitant/palonosetron (300 mg/0.50 mg) fixed-dose combination
dexamethasone: Oral dexamethasone (12 mg)
|
|---|---|---|
|
Number of Participants With Treatment-emergent AEs at Cycle 1
|
121 Participants
|
122 Participants
|
PRIMARY outcome
Timeframe: At the end of Cycle 4 (each cycle is 21 days)Outcome measures
| Measure |
Test Group
n=200 Participants
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)
fosnetupitant/ palonosetron: intravenous fosnetupitant/ palonosetron (260 mg/0.25 mg) fixed-dose combination
dexamethasone: Oral dexamethasone (12 mg)
|
Control Group
n=202 Participants
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)
netupitant/palonosetron: oral netupitant/palonosetron (300 mg/0.50 mg) fixed-dose combination
dexamethasone: Oral dexamethasone (12 mg)
|
|---|---|---|
|
Number of Participants With Treatment-emergent AEs All Cycles
|
184 Participants
|
187 Participants
|
PRIMARY outcome
Timeframe: At the end of Cycle 4 (each cycle is 21 days)Outcome measures
| Measure |
Test Group
n=200 Participants
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)
fosnetupitant/ palonosetron: intravenous fosnetupitant/ palonosetron (260 mg/0.25 mg) fixed-dose combination
dexamethasone: Oral dexamethasone (12 mg)
|
Control Group
n=202 Participants
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)
netupitant/palonosetron: oral netupitant/palonosetron (300 mg/0.50 mg) fixed-dose combination
dexamethasone: Oral dexamethasone (12 mg)
|
|---|---|---|
|
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
|
37 Participants
|
29 Participants
|
PRIMARY outcome
Timeframe: At the end of Cycle 4 (each cycle is 21 days)Outcome measures
| Measure |
Test Group
n=200 Participants
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)
fosnetupitant/ palonosetron: intravenous fosnetupitant/ palonosetron (260 mg/0.25 mg) fixed-dose combination
dexamethasone: Oral dexamethasone (12 mg)
|
Control Group
n=202 Participants
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)
netupitant/palonosetron: oral netupitant/palonosetron (300 mg/0.50 mg) fixed-dose combination
dexamethasone: Oral dexamethasone (12 mg)
|
|---|---|---|
|
Number of Participants With Study-Drug-Related TEAEs Reported for ≥2% of Patients in Either Treatment Group Throughout the Study
|
16 Participants
|
22 Participants
|
SECONDARY outcome
Timeframe: 24 hours after the start of AC chemotherapy administrationdefined as no emetic episodes \[vomit or retch\] and no rescue medication
Outcome measures
| Measure |
Test Group
n=200 Participants
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)
fosnetupitant/ palonosetron: intravenous fosnetupitant/ palonosetron (260 mg/0.25 mg) fixed-dose combination
dexamethasone: Oral dexamethasone (12 mg)
|
Control Group
n=202 Participants
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)
netupitant/palonosetron: oral netupitant/palonosetron (300 mg/0.50 mg) fixed-dose combination
dexamethasone: Oral dexamethasone (12 mg)
|
|---|---|---|
|
Complete Response in Cycle 1 During the Acute Phase
|
173 Participants
|
179 Participants
|
SECONDARY outcome
Timeframe: 120 hour after the start of AC chemotherapy administrationdefined as no emetic episodes \[vomit or retch\] and no rescue medication
Outcome measures
| Measure |
Test Group
n=200 Participants
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)
fosnetupitant/ palonosetron: intravenous fosnetupitant/ palonosetron (260 mg/0.25 mg) fixed-dose combination
dexamethasone: Oral dexamethasone (12 mg)
|
Control Group
n=202 Participants
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)
netupitant/palonosetron: oral netupitant/palonosetron (300 mg/0.50 mg) fixed-dose combination
dexamethasone: Oral dexamethasone (12 mg)
|
|---|---|---|
|
Complete Response in Cycle 1 During the Delayed Phase
|
151 Participants
|
159 Participants
|
SECONDARY outcome
Timeframe: 0-120 hours after the start of AC chemotherapydefined as no emetic episodes \[vomit or retch\] and no rescue medication
Outcome measures
| Measure |
Test Group
n=200 Participants
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)
fosnetupitant/ palonosetron: intravenous fosnetupitant/ palonosetron (260 mg/0.25 mg) fixed-dose combination
dexamethasone: Oral dexamethasone (12 mg)
|
Control Group
n=202 Participants
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)
netupitant/palonosetron: oral netupitant/palonosetron (300 mg/0.50 mg) fixed-dose combination
dexamethasone: Oral dexamethasone (12 mg)
|
|---|---|---|
|
Complete Response in Cycle 1 During the Overall Phase
|
146 Participants
|
156 Participants
|
SECONDARY outcome
Timeframe: cycle 1Percentage (including two-sided 95% CI using Wilson score method) of patients with NIDL based on FLIE scores (overall, by domain, and by individual item) are summarized by treatment group. NIDL was defined as a score greater than 108 points, 54 points, and 6 points for total FLIE score, domain score, and single item score, respectively. Differences between treatment groups for total FLIE score and domain scores (nausea and vomiting) were presented with two-sided 95% CIs using the CMH method adjusted for region and age class strata and also using Newcombe-Wilson's method without strata adjustment. No Impact on Daily Life (NIDL) Based on Functional Living Index-Emesis (FLIE) Scores. The FLIE is a nausea and vomiting specific self report instrument comprised of two domains (nausea and vomiting) with nine identical items in each domain
Outcome measures
| Measure |
Test Group
n=200 Participants
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)
fosnetupitant/ palonosetron: intravenous fosnetupitant/ palonosetron (260 mg/0.25 mg) fixed-dose combination
dexamethasone: Oral dexamethasone (12 mg)
|
Control Group
n=202 Participants
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)
netupitant/palonosetron: oral netupitant/palonosetron (300 mg/0.50 mg) fixed-dose combination
dexamethasone: Oral dexamethasone (12 mg)
|
|---|---|---|
|
Overall Percentage of Patients With NIDL Based on FLIE Scores for Cycles 1
Vomiting domain score
|
87.5 percentage of participants
Interval 82.2 to 91.4
|
90.6 percentage of participants
Interval 85.8 to 93.9
|
|
Overall Percentage of Patients With NIDL Based on FLIE Scores for Cycles 1
total score
|
74.0 percentage of participants
Interval 67.5 to 79.6
|
78.7 percentage of participants
Interval 72.6 to 83.8
|
|
Overall Percentage of Patients With NIDL Based on FLIE Scores for Cycles 1
Nausea domain score
|
67.5 percentage of participants
Interval 60.7 to 73.6
|
68.3 percentage of participants
Interval 61.7 to 74.3
|
Adverse Events
Test Group
Serious events: 5 serious events
Other events: 184 other events
Deaths: 0 deaths
Control Group
Serious events: 4 serious events
Other events: 187 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Test Group
n=200 participants at risk
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)
fosnetupitant/ palonosetron: intravenous fosnetupitant/ palonosetron (260 mg/0.25 mg) fixed-dose combination
dexamethasone: Oral dexamethasone (12 mg)
|
Control Group
n=202 participants at risk
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)
netupitant/palonosetron: oral netupitant/palonosetron (300 mg/0.50 mg) fixed-dose combination
dexamethasone: Oral dexamethasone (12 mg)
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.50%
1/200 • from screening (day -14) to end of follow up (Day 22) of Cycle 4
|
0.50%
1/202 • from screening (day -14) to end of follow up (Day 22) of Cycle 4
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.50%
1/200 • from screening (day -14) to end of follow up (Day 22) of Cycle 4
|
0.50%
1/202 • from screening (day -14) to end of follow up (Day 22) of Cycle 4
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.00%
0/200 • from screening (day -14) to end of follow up (Day 22) of Cycle 4
|
0.50%
1/202 • from screening (day -14) to end of follow up (Day 22) of Cycle 4
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/200 • from screening (day -14) to end of follow up (Day 22) of Cycle 4
|
0.50%
1/202 • from screening (day -14) to end of follow up (Day 22) of Cycle 4
|
|
Gastrointestinal disorders
Vomiting
|
0.50%
1/200 • from screening (day -14) to end of follow up (Day 22) of Cycle 4
|
0.00%
0/202 • from screening (day -14) to end of follow up (Day 22) of Cycle 4
|
|
General disorders
Pyrexia
|
0.50%
1/200 • from screening (day -14) to end of follow up (Day 22) of Cycle 4
|
0.00%
0/202 • from screening (day -14) to end of follow up (Day 22) of Cycle 4
|
|
Hepatobiliary disorders
Biliary colic
|
0.50%
1/200 • from screening (day -14) to end of follow up (Day 22) of Cycle 4
|
0.00%
0/202 • from screening (day -14) to end of follow up (Day 22) of Cycle 4
|
|
Infections and infestations
Urinary tract infection
|
0.50%
1/200 • from screening (day -14) to end of follow up (Day 22) of Cycle 4
|
0.50%
1/202 • from screening (day -14) to end of follow up (Day 22) of Cycle 4
|
|
Infections and infestations
Clostridium difficile colitis
|
0.00%
0/200 • from screening (day -14) to end of follow up (Day 22) of Cycle 4
|
0.50%
1/202 • from screening (day -14) to end of follow up (Day 22) of Cycle 4
|
|
Infections and infestations
Erysipelas
|
0.50%
1/200 • from screening (day -14) to end of follow up (Day 22) of Cycle 4
|
0.00%
0/202 • from screening (day -14) to end of follow up (Day 22) of Cycle 4
|
Other adverse events
| Measure |
Test Group
n=200 participants at risk
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)
fosnetupitant/ palonosetron: intravenous fosnetupitant/ palonosetron (260 mg/0.25 mg) fixed-dose combination
dexamethasone: Oral dexamethasone (12 mg)
|
Control Group
n=202 participants at risk
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)
netupitant/palonosetron: oral netupitant/palonosetron (300 mg/0.50 mg) fixed-dose combination
dexamethasone: Oral dexamethasone (12 mg)
|
|---|---|---|
|
Blood and lymphatic system disorders
Leukopenia
|
20.0%
40/200 • from screening (day -14) to end of follow up (Day 22) of Cycle 4
|
16.3%
33/202 • from screening (day -14) to end of follow up (Day 22) of Cycle 4
|
|
Blood and lymphatic system disorders
Anaemia
|
15.5%
31/200 • from screening (day -14) to end of follow up (Day 22) of Cycle 4
|
11.9%
24/202 • from screening (day -14) to end of follow up (Day 22) of Cycle 4
|
|
Blood and lymphatic system disorders
Neutropenia
|
12.5%
25/200 • from screening (day -14) to end of follow up (Day 22) of Cycle 4
|
11.9%
24/202 • from screening (day -14) to end of follow up (Day 22) of Cycle 4
|
|
Gastrointestinal disorders
Nausea
|
7.0%
14/200 • from screening (day -14) to end of follow up (Day 22) of Cycle 4
|
4.5%
9/202 • from screening (day -14) to end of follow up (Day 22) of Cycle 4
|
|
Gastrointestinal disorders
Diarrhoea
|
5.0%
10/200 • from screening (day -14) to end of follow up (Day 22) of Cycle 4
|
4.5%
9/202 • from screening (day -14) to end of follow up (Day 22) of Cycle 4
|
|
General disorders
Fatigue
|
15.0%
30/200 • from screening (day -14) to end of follow up (Day 22) of Cycle 4
|
16.8%
34/202 • from screening (day -14) to end of follow up (Day 22) of Cycle 4
|
|
General disorders
Asthenia
|
13.5%
27/200 • from screening (day -14) to end of follow up (Day 22) of Cycle 4
|
8.4%
17/202 • from screening (day -14) to end of follow up (Day 22) of Cycle 4
|
|
Investigations
Gamma-glutamyltransferase increased
|
5.5%
11/200 • from screening (day -14) to end of follow up (Day 22) of Cycle 4
|
3.5%
7/202 • from screening (day -14) to end of follow up (Day 22) of Cycle 4
|
|
Nervous system disorders
Headache
|
5.0%
10/200 • from screening (day -14) to end of follow up (Day 22) of Cycle 4
|
5.9%
12/202 • from screening (day -14) to end of follow up (Day 22) of Cycle 4
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
71.5%
143/200 • from screening (day -14) to end of follow up (Day 22) of Cycle 4
|
68.3%
138/202 • from screening (day -14) to end of follow up (Day 22) of Cycle 4
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place