Trial Outcomes & Findings for Aprepitant's Effect on Drug Metabolism in Multi-Day Combination (CHOP/R-CHOP) Chemotherapy Regimen in Lymphoma Patients (NCT NCT00651755)
NCT ID: NCT00651755
Last Updated: 2013-07-02
Results Overview
Pharmacokinetic (PK) blood sampling to determine the geometric mean AUC of Cyclophosphamide (CP) during \& post chemotherapy infusion, baseline, at 30, 60, 75, 90 minutes, and 2 , 4, 6, 8, and 24 hours from start of cyclophosphamide infusion. The absence of PK drug interactions was determined if the 90% Confidence Intervals (CI) of the geometric mean AUC ratio between 2 groups is within 0.80 to 1.25. Measurements reported as concentrate times the time, i.e. micrograms (ug)/milliliters (mL) times hour (hr).
COMPLETED
NA
23 participants
Time points over 24 hours of cyclophosphamide infusion for both cycles (21 day cycle)
2013-07-02
Participant Flow
Recruitment Period: March 14, 2008 to May 3, 2010. All recruitment done at The University of Texas MD Anderson Cancer Center.
Of the 23 participants who enrolled, three (3) withdrew prior to group assignment and were excluded from the trial.
Participant milestones
| Measure |
First Aprepitant Cycle 1 Then No Aprepitant Cycle 2
First Aprepitant with CHOP or R-CHOP (CHOP plus Rituximab 375 mg/m\^2 intravenous Day 1) then No Aprepitant in Cycle 2.
Aprepitant 125 mg oral (PO) Day 1 of Cycle 1 followed by 80 mg PO Daily Days 2-3 with CHOP (steroid in CHOP) or R-CHOP plus Rituximab 375 mg/m\^2 intravenous Day 1. CHOP or R-CHOP chemotherapy: (1) bolus or 48-hour infusion CHOP \[cyclophosphamide 750 mg/m\^2 IV Day 1, doxorubicin 25 mg/m\^2/day IV given bolus or over 48 hours continuous infusion Days 1-2, vincristine 2 mg IV Day 1, prednisone PO 100 mg \* 5 days\]; or (2) Bolus or 48-hour infusion R-CHOP \[Rituximab 375 mg/m\^2 on Day 1 + CHOP as above\].
|
First No Aprepritant Cycle 1, Then Aprepitant Cycle 2
First No Aprepitant in Cycle 1, then Aprepitant 125 mg oral (PO) Day 1 of Cycle 2 followed by 80 mg PO Daily Days 2-3 with CHOP (steroid in CHOP) or R-CHOP plus Rituximab 375 mg/m\^2 intravenous Day 1. CHOP or R-CHOP chemotherapy: (1) bolus or 48-hour infusion CHOP \[cyclophosphamide 750 mg/m\^2 IV Day 1, doxorubicin 25 mg/m\^2/day IV given bolus or over 48 hours continuous infusion Days 1-2, vincristine 2 mg IV Day 1, prednisone PO 100 mg \* 5 days\]; or (2) Bolus or 48-hour infusion R-CHOP \[Rituximab 375 mg/m\^2 on Day 1 + CHOP as above\].
|
|---|---|---|
|
Cycle 1 (First 21 Days)
STARTED
|
11
|
9
|
|
Cycle 1 (First 21 Days)
COMPLETED
|
10
|
9
|
|
Cycle 1 (First 21 Days)
NOT COMPLETED
|
1
|
0
|
|
Cycle 2 (Second 21 Days)
STARTED
|
10
|
9
|
|
Cycle 2 (Second 21 Days)
COMPLETED
|
10
|
8
|
|
Cycle 2 (Second 21 Days)
NOT COMPLETED
|
0
|
1
|
Reasons for withdrawal
| Measure |
First Aprepitant Cycle 1 Then No Aprepitant Cycle 2
First Aprepitant with CHOP or R-CHOP (CHOP plus Rituximab 375 mg/m\^2 intravenous Day 1) then No Aprepitant in Cycle 2.
Aprepitant 125 mg oral (PO) Day 1 of Cycle 1 followed by 80 mg PO Daily Days 2-3 with CHOP (steroid in CHOP) or R-CHOP plus Rituximab 375 mg/m\^2 intravenous Day 1. CHOP or R-CHOP chemotherapy: (1) bolus or 48-hour infusion CHOP \[cyclophosphamide 750 mg/m\^2 IV Day 1, doxorubicin 25 mg/m\^2/day IV given bolus or over 48 hours continuous infusion Days 1-2, vincristine 2 mg IV Day 1, prednisone PO 100 mg \* 5 days\]; or (2) Bolus or 48-hour infusion R-CHOP \[Rituximab 375 mg/m\^2 on Day 1 + CHOP as above\].
|
First No Aprepritant Cycle 1, Then Aprepitant Cycle 2
First No Aprepitant in Cycle 1, then Aprepitant 125 mg oral (PO) Day 1 of Cycle 2 followed by 80 mg PO Daily Days 2-3 with CHOP (steroid in CHOP) or R-CHOP plus Rituximab 375 mg/m\^2 intravenous Day 1. CHOP or R-CHOP chemotherapy: (1) bolus or 48-hour infusion CHOP \[cyclophosphamide 750 mg/m\^2 IV Day 1, doxorubicin 25 mg/m\^2/day IV given bolus or over 48 hours continuous infusion Days 1-2, vincristine 2 mg IV Day 1, prednisone PO 100 mg \* 5 days\]; or (2) Bolus or 48-hour infusion R-CHOP \[Rituximab 375 mg/m\^2 on Day 1 + CHOP as above\].
|
|---|---|---|
|
Cycle 1 (First 21 Days)
Withdrawal by Subject
|
1
|
0
|
|
Cycle 2 (Second 21 Days)
Not Evaluable
|
0
|
1
|
Baseline Characteristics
Aprepitant's Effect on Drug Metabolism in Multi-Day Combination (CHOP/R-CHOP) Chemotherapy Regimen in Lymphoma Patients
Baseline characteristics by cohort
| Measure |
Entire Study Population
n=20 Participants
Participants randomized to Aprepitant or control (Standard of Care) in Cycle 1 crossover for different treatment in Cycle 2.
|
|---|---|
|
Age Continuous
|
58 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
11 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
9 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
20 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Time points over 24 hours of cyclophosphamide infusion for both cycles (21 day cycle)Population: There were 18 participants eligible for PK analysis, one was excluded from the final analysis due to data issues.
Pharmacokinetic (PK) blood sampling to determine the geometric mean AUC of Cyclophosphamide (CP) during \& post chemotherapy infusion, baseline, at 30, 60, 75, 90 minutes, and 2 , 4, 6, 8, and 24 hours from start of cyclophosphamide infusion. The absence of PK drug interactions was determined if the 90% Confidence Intervals (CI) of the geometric mean AUC ratio between 2 groups is within 0.80 to 1.25. Measurements reported as concentrate times the time, i.e. micrograms (ug)/milliliters (mL) times hour (hr).
Outcome measures
| Measure |
Aprepitant
n=17 Participants
Crossover study where participants received Aprepitant 125 mg oral (PO) Day 1 in Cycle 1 and received standard of care in Cycle 2. Or participants received no Aprepitant in Cycle 1, Aprepitant 125 mg oral (PO) Day 1 in Cycle 2.
|
Control Group
n=17 Participants
Crossover study where participants received Standard of care in cycle 1 or cycle 2.
|
|---|---|---|
|
Geometric Mean Area Under Curve (AUC) of Analyte, Cyclophosphamide (CP), in Aprepitant Treatment and Control Group
|
300 ug/mL*hr
Interval 276.0 to 326.0
|
250 ug/mL*hr
Interval 227.0 to 277.0
|
PRIMARY outcome
Timeframe: Time points over 24 hours of cyclophosphamide infusion for both cycles (21 day cycle)Population: There were 18 participants eligible for PK analysis, one was excluded from the final analysis due to data issues.
Pharmacokinetic (PK) blood sampling to determine the geometric mean AUC of 2-deCI-CP, during \& post chemotherapy infusion, baseline, at 30, 60, 75, 90 minutes, and 2 , 4, 6, 8, and 24 hours from start of cyclophosphamide infusion. The absence of PK drug interactions was determined if the 90% Confidence Intervals (CI) of the geometric mean AUC ratio between 2 groups is within 0.80 to 1.25. Measurements reported as concentrate times the time, i.e. micrograms (ug)/milliliters (mL) times hour (hr).
Outcome measures
| Measure |
Aprepitant
n=17 Participants
Crossover study where participants received Aprepitant 125 mg oral (PO) Day 1 in Cycle 1 and received standard of care in Cycle 2. Or participants received no Aprepitant in Cycle 1, Aprepitant 125 mg oral (PO) Day 1 in Cycle 2.
|
Control Group
n=17 Participants
Crossover study where participants received Standard of care in cycle 1 or cycle 2.
|
|---|---|---|
|
Geometric Mean Area Under Curve (AUC) of Analyte, 2-dechloro-cyclophosphamide(2-deCI-CP), in Aprepitant Treatment and Control Group
|
4.5 ug/mL*hr
Interval 3.7 to 5.4
|
6.0 ug/mL*hr
Interval 4.8 to 7.5
|
PRIMARY outcome
Timeframe: Time points over 24 hours of cyclophosphamide infusion for both cycles (21 day cycle)Population: There were 18 participants eligible for PK analysis, one was excluded from the final analysis due to data issues.
Pharmacokinetic (PK) blood sampling to determine the geometric mean AUC of 4-hydroxy-cyclophosphamide (4-OH-CP), during \& post chemotherapy infusion, baseline, at 30, 60, 75, 90 minutes, and 2 , 4, 6, 8, and 24 hours from start of cyclophosphamide infusion. The absence of PK drug interactions was determined if the 90% Confidence Intervals (CI) of the geometric mean AUC ratio between 2 groups is within 0.80 to 1.25. Measurements reported as concentrate times the time, i.e. micrograms (ug)/milliliters (mL) times hour (hr).
Outcome measures
| Measure |
Aprepitant
n=17 Participants
Crossover study where participants received Aprepitant 125 mg oral (PO) Day 1 in Cycle 1 and received standard of care in Cycle 2. Or participants received no Aprepitant in Cycle 1, Aprepitant 125 mg oral (PO) Day 1 in Cycle 2.
|
Control Group
n=17 Participants
Crossover study where participants received Standard of care in cycle 1 or cycle 2.
|
|---|---|---|
|
Geometric Mean Area Under Curve (AUC) of Analyte, 4-hydroxy-cyclophosphamide (4-OH-CP), in Aprepitant Treatment and Control Group
|
3.9 ug/mL*hr
Interval 3.4 to 4.4
|
4.0 ug/mL*hr
Interval 3.4 to 4.7
|
PRIMARY outcome
Timeframe: Time points over 24 hours of cyclophosphamide infusion for both cycles (21 day cycle)Population: There were 18 patients eligible for PK analysis, two participants were excluded from the analysis due to data issues.
Pharmacokinetic (PK) blood sampling to determine the geometric mean AUC of VC, during \& post chemotherapy infusion, baseline, at 30, 60, 75, 90 minutes, and 2 , 4, 6, 8, and 24 hours from start of cyclophosphamide infusion. The absence of PK drug interactions was determined if the 90% Confidence Intervals (CI) of the geometric mean AUC ratio between 2 groups is within 0.80 to 1.25. Measurements reported as concentrate times the time, i.e. nanograms (ng)/milliliters (mL) times hour (hr).
Outcome measures
| Measure |
Aprepitant
n=16 Participants
Crossover study where participants received Aprepitant 125 mg oral (PO) Day 1 in Cycle 1 and received standard of care in Cycle 2. Or participants received no Aprepitant in Cycle 1, Aprepitant 125 mg oral (PO) Day 1 in Cycle 2.
|
Control Group
n=16 Participants
Crossover study where participants received Standard of care in cycle 1 or cycle 2.
|
|---|---|---|
|
Geometric Mean Area Under Curve (AUC) of Analyte, Vincristine (VC), in Aprepitant Treatment and Control Group
|
41 ng/mL*hr
Interval 34.0 to 49.0
|
39 ng/mL*hr
Interval 34.0 to 46.0
|
PRIMARY outcome
Timeframe: Time points over 8 hours of cyclophosphamide infusion for both cycles (21 day cycle)Population: Per protocol, 18 participants were eligible for PK analysis.
Pharmacokinetic (PK) blood sampling to determine the geometric mean AUC of PR, during \& post chemotherapy infusion, baseline, at 30, 60, 75, 90 minutes, and 2 , 4, 6, 8, and 24 hours from start of cyclophosphamide infusion. The absence of PK drug interactions was determined if the 90% Confidence Intervals (CI) of the geometric mean AUC ratio between 2 groups is within 0.80 to 1.25. Measurements reported as concentrate times the time, i.e. nanograms (ng)/milliliters (mL) times hour (hr).
Outcome measures
| Measure |
Aprepitant
n=18 Participants
Crossover study where participants received Aprepitant 125 mg oral (PO) Day 1 in Cycle 1 and received standard of care in Cycle 2. Or participants received no Aprepitant in Cycle 1, Aprepitant 125 mg oral (PO) Day 1 in Cycle 2.
|
Control Group
n=18 Participants
Crossover study where participants received Standard of care in cycle 1 or cycle 2.
|
|---|---|---|
|
Geometric Mean Area Under Curve (AUC) of Analyte,Prednisone (PR), in Aprepitant Treatment and Control Group
|
287 ng/mL*hr
Interval 262.0 to 315.0
|
265 ng/mL*hr
Interval 243.0 to 289.0
|
PRIMARY outcome
Timeframe: Time points over 8 hours of cyclophosphamide infusion for both cycles (21 day cycle)Population: Per protocol, 18 participants were eligible for PK analysis.
Pharmacokinetic (PK) blood sampling to determine the geometric mean AUC of PL, during \& post chemotherapy infusion, baseline, at 30, 60, 75, 90 minutes, and 2 , 4, 6, 8, and 24 hours from start of cyclophosphamide infusion. The absence of PK drug interactions was determined if the 90% Confidence Intervals (CI) of the geometric mean AUC ratio between 2 groups is within 0.80 to 1.25. Measurements reported as concentrate times the time, i.e. nanograms (ng)/milliliters (mL) times hour (hr).
Outcome measures
| Measure |
Aprepitant
n=18 Participants
Crossover study where participants received Aprepitant 125 mg oral (PO) Day 1 in Cycle 1 and received standard of care in Cycle 2. Or participants received no Aprepitant in Cycle 1, Aprepitant 125 mg oral (PO) Day 1 in Cycle 2.
|
Control Group
n=18 Participants
Crossover study where participants received Standard of care in cycle 1 or cycle 2.
|
|---|---|---|
|
Geometric Mean Area Under Curve (AUC) of Analyte, Prednisolone (PL), in Aprepitant Treatment and Control Group
|
4416 ng/mL*hr
Interval 4027.0 to 4842.0
|
3817 ng/mL*hr
Interval 3324.0 to 4382.0
|
Adverse Events
Aprepitant
Control
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Aprepitant
n=20 participants at risk
Aprepitant 125 mg oral (PO) Day 1 (Cycle 1 or Cycle 2) to include treated study population.
|
Control
n=20 participants at risk
Standard of Care
|
|---|---|---|
|
General disorders
Headache
|
30.0%
6/20 • Number of events 6 • 1 year, 11 months
|
0.00%
0/20 • 1 year, 11 months
|
|
General disorders
Fatigue
|
15.0%
3/20 • Number of events 3 • 1 year, 11 months
|
5.0%
1/20 • Number of events 1 • 1 year, 11 months
|
|
Gastrointestinal disorders
Constipation
|
15.0%
3/20 • Number of events 3 • 1 year, 11 months
|
5.0%
1/20 • Number of events 1 • 1 year, 11 months
|
Additional Information
Saroj Vadhan-Raj, MD / Professor
University of Texas MD Anderson Cancer Center
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place