Chemotherapy-induced Neutropenia
Conditions
Brief summary
Determination of the effect of neugranin on the duration and severity of severe neutropenia in participants receiving doxorubicin in combination with docetaxel.
Interventions
BIOLOGICALNeugranin
Neugranin will be administered per dose and schedule specified in the arm description.
BIOLOGICALPegfilgrastim
Pegfilgrastim will be administered per dose and schedule specified in the arm description.
DRUGChemotherapy
The chemotherapy regimen for this trial consists of doxorubicin 60 mg/m\^2 and docetaxel 75 mg/m\^2 in combination
Sponsors
Teva Branded Pharmaceutical Products R&D, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Breast cancer participants scheduled to receive the AT regimen (doxorubicin/ docetaxel)
Exclusion criteria
* Participants may have received no more than 1 prior chemotherapy regimen (including adjuvant therapy if given within the last 12 months)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Double-Blind Phase: Duration of Severe Neutropenia in Cycle 1 | Cycle 1 (cycle length = 21 days) | Severe neutropenia was defined as Grade 4 neutropenia (absolute neutrophil count \[ANC\] \<0.5 x 10\^9/liter \[L\]). The duration of severe neutropenia was calculated by cycle as the number of days from the first day in which the ANC fell below 0.5 x 10\^9/L after beginning a chemotherapy cycle until the participant had an ANC ≥0.5 x 10\^9/L within the cycle. |
| Open-Label Phase: Duration of Severe Neutropenia in Cycle 1 | Cycle 1 (cycle length = 21 days) | Severe neutropenia was defined as Grade 4 neutropenia (ANC \<0.5 x 10\^9/L). The duration of severe neutropenia was calculated by cycle as the number of days from the first day in which the ANC fell below 0.5 x 10\^9/L after beginning a chemotherapy cycle until the participant had an ANC ≥0.5 x 10\^9/L within the cycle. There was no planned statistical analysis for the open-label phase arm. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Double-Blind Phase: Number of Participants With Febrile Neutropenia | Cycles 1-4 (each cycle = 21 days) | Febrile neutropenia was defined as an imputed or observed ANC \<0.5 x 10\^9/L and body temperature \>38.5 degrees celsius (°C) occurring on the same day and for more than one hour (axillary measurement). Number of participants with febrile neutropenia over all cycles (Cycles 1 to 4) has been reported. |
| Open-Label Phase: Number of Participants With Febrile Neutropenia | Cycles 1-4 (each cycle = 21 days) | Febrile neutropenia was defined as an imputed or observed ANC \<0.5 x 10\^9/L and body temperature \>38.5 °C occurring on the same day and for more than one hour (axillary measurement). Number of participants with febrile neutropenia over all cycles (Cycles 1 to 4) has been reported. |
Countries
Bulgaria, Romania, Russia, Serbia, Ukraine
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Double-Blind Phase: Pegfilgrastim Participants received pegfilgrastim 6 mg, administered by SC injection once per chemotherapy cycle (approximately 24 hours after chemotherapy administration) for up to 4 cycles (each cycle length = 21 days). The chemotherapy regimen consisted of doxorubicin 60 mg/m\^2 and docetaxel 75 mg/m\^2 administered sequentially by IV infusion on Day 1 of treatment for up to four 21-day cycles. | 151 |
| Double-Blind Phase: Neugranin 40 mg Participants received neugranin 40 mg, administered by SC injection once per chemotherapy cycle (approximately 24 hours after chemotherapy administration) for up to 4 cycles (each cycle length = 21 days). The chemotherapy regimen consisted of doxorubicin 60 mg/m\^2 and docetaxel 75 mg/m\^2 administered sequentially by IV infusion on Day 1 of treatment for up to four 21-day cycles. | 153 |
| Open-Label Phase: Neugranin 40 mg Participants received neugranin 40 mg, administered by SC injection once per chemotherapy cycle (approximately 24 hours after chemotherapy administration) for up to 4 cycles (each cycle length = 21 days). The chemotherapy regimen consisted of doxorubicin 60 mg/m\^2 and docetaxel 75 mg/m\^2 administered sequentially by IV infusion on Day 1 of treatment for up to four 21-day cycles. | 77 |
| Total | 381 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Double-Blind Phase | Adverse Event | 1 | 2 | 0 |
| Double-Blind Phase | Death | 0 | 1 | 0 |
| Double-Blind Phase | Lost to Follow-up | 1 | 3 | 0 |
| Double-Blind Phase | Non-compliance | 1 | 0 | 0 |
| Double-Blind Phase | Request of Investigator | 1 | 0 | 0 |
| Double-Blind Phase | Treatment Failure/Disease Progression | 0 | 4 | 0 |
| Double-Blind Phase | Withdrawal by Subject | 2 | 5 | 0 |
| Open-Label Phase | Adverse Event | 0 | 0 | 4 |
| Open-Label Phase | Death | 0 | 0 | 1 |
| Open-Label Phase | Withdrawal by Subject | 0 | 0 | 6 |
Baseline characteristics
| Characteristic | Double-Blind Phase: Pegfilgrastim | Double-Blind Phase: Neugranin 40 mg | Open-Label Phase: Neugranin 40 mg | Total |
|---|---|---|---|---|
| Age, Continuous | 50.8 years STANDARD_DEVIATION 9.65 | 51.5 years STANDARD_DEVIATION 10.28 | 52.2 years STANDARD_DEVIATION 10.22 | 51.4 years STANDARD_DEVIATION 10 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 151 Participants | 153 Participants | 77 Participants | 381 Participants |
| Sex: Female, Male Female | 151 Participants | 153 Participants | 77 Participants | 381 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 150 | 2 / 153 | 2 / 77 |
| other Total, other adverse events | 134 / 150 | 139 / 153 | 71 / 77 |
| serious Total, serious adverse events | 7 / 150 | 6 / 153 | 6 / 77 |
Outcome results
Primary
Double-Blind Phase: Duration of Severe Neutropenia in Cycle 1
Severe neutropenia was defined as Grade 4 neutropenia (absolute neutrophil count \[ANC\] \<0.5 x 10\^9/liter \[L\]). The duration of severe neutropenia was calculated by cycle as the number of days from the first day in which the ANC fell below 0.5 x 10\^9/L after beginning a chemotherapy cycle until the participant had an ANC ≥0.5 x 10\^9/L within the cycle.
Time frame: Cycle 1 (cycle length = 21 days)
Population: Per protocol (PP) population included all data from randomized participants that were obtained prior to experiencing major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Double-Blind Phase: Pegfilgrastim | Double-Blind Phase: Duration of Severe Neutropenia in Cycle 1 | 1.0 days | Standard Deviation 1.08 |
| Double-Blind Phase: Neugranin 40 mg | Double-Blind Phase: Duration of Severe Neutropenia in Cycle 1 | 1.1 days | Standard Deviation 1.13 |
Comparison: For the primary non-inferiority endpoint of cycle 1 DSN, the 95% confidence interval (CI) for difference in DSN was calculated by stratified bootstrap resampling.95% CI: [-0.13, 0.37]
Primary
Open-Label Phase: Duration of Severe Neutropenia in Cycle 1
Severe neutropenia was defined as Grade 4 neutropenia (ANC \<0.5 x 10\^9/L). The duration of severe neutropenia was calculated by cycle as the number of days from the first day in which the ANC fell below 0.5 x 10\^9/L after beginning a chemotherapy cycle until the participant had an ANC ≥0.5 x 10\^9/L within the cycle. There was no planned statistical analysis for the open-label phase arm.
Time frame: Cycle 1 (cycle length = 21 days)
Population: PP population included all data from randomized participants that were obtained prior to experiencing major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Double-Blind Phase: Pegfilgrastim | Open-Label Phase: Duration of Severe Neutropenia in Cycle 1 | 1.0 days | Standard Deviation 1.03 |
Secondary
Double-Blind Phase: Number of Participants With Febrile Neutropenia
Febrile neutropenia was defined as an imputed or observed ANC \<0.5 x 10\^9/L and body temperature \>38.5 degrees celsius (°C) occurring on the same day and for more than one hour (axillary measurement). Number of participants with febrile neutropenia over all cycles (Cycles 1 to 4) has been reported.
Time frame: Cycles 1-4 (each cycle = 21 days)
Population: PP population included all data from randomized participants that were obtained prior to experiencing major protocol violations.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Double-Blind Phase: Pegfilgrastim | Double-Blind Phase: Number of Participants With Febrile Neutropenia | 4 participants |
| Double-Blind Phase: Neugranin 40 mg | Double-Blind Phase: Number of Participants With Febrile Neutropenia | 2 participants |
Secondary
Open-Label Phase: Number of Participants With Febrile Neutropenia
Febrile neutropenia was defined as an imputed or observed ANC \<0.5 x 10\^9/L and body temperature \>38.5 °C occurring on the same day and for more than one hour (axillary measurement). Number of participants with febrile neutropenia over all cycles (Cycles 1 to 4) has been reported.
Time frame: Cycles 1-4 (each cycle = 21 days)
Population: PP population included all data from randomized participants that were obtained prior to experiencing major protocol violations.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Double-Blind Phase: Pegfilgrastim | Open-Label Phase: Number of Participants With Febrile Neutropenia | 2 participants |