Breast Cancer, Neutropenia
Conditions
Keywords
Neutropenia, Breast Cancer, Long-acting Granulocyte Colony Stimulating Factor, Early Stage Breast Cancer, Docetaxel + Cyclophosphamide (TC) chemotherapy
Brief summary
The purpose of this study is to compare the efficacy of SPI-2012 versus pegfilgrastim in participants with early-stage breast cancer receiving docetaxel and cyclophosphamide (TC) as measured by the duration of severe neutropenia (DSN).
Detailed description
This is a Phase 3, randomized, open-label, active-controlled, multicenter study to compare the efficacy and safety of SPI-2012 versus pegfilgrastim in participants with early-stage breast cancer treated with TC chemotherapy as measured by the duration of severe neutropenia (DSN). Each cycle was 21 days. Four cycles were evaluated for this study. On Day 1 of each cycle, participants received TC chemotherapy. On Day 2 of each cycle, participants received study drug (SPI-2012 or pegfilgrastim). After cycle 1, as applicable, participants who received at least one dose of study drug will be followed for safety for 12 months after the last dose of study treatment.
Interventions
DRUGSPI-2012
Supplied in prefilled single-use syringes for subcutaneous injection, administered on Day 2 of each cycle
DRUGPegfilgrastim
Subcutaneous injection administered on Day 2 of each cycle.
DRUGDocetaxel
75mg/m\^2 IV infusion administered on Day 1 of each cycle
DRUGCyclophosphamide
600mg/m\^2 IV infusion administered on Day 1 of each cycle
Sponsors
Spectrum Pharmaceuticals, Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * New diagnosis of histologically confirmed early-stage breast cancer (ESBC), defined as operable Stage I to Stage IIIA breast cancer * Candidate for adjuvant or neo-adjuvant TC chemotherapy * Eastern Cooperative Oncology Group (ECOG) performance status \<= 2 * Absolute neutrophil count (ANC) \>=1.5×10\^9/L * Platelet count \>=100×10\^9/L * Hemoglobin \>9 g/dL * Calculated creatinine clearance \> 50 mL/min * Total bilirubin \<=1.5 mg/dL * Aspartate aminotransferase (AST) / Serum glutamic oxaloacetic transaminase (SGOT) and Alanine aminotransferase (ALT)/Serum glutamic pyruvic transaminase (SGPT) \<=2.5×ULN (upper limit of normal) * Alkaline phosphatase \<=2.0×ULN Key
Exclusion criteria
* Active concurrent malignancy (except non melanoma skin cancer or carcinoma in situ of the cervix) or life-threatening disease * Locally recurrent/metastatic breast cancer * Known sensitivity to E. coli-derived products * Concurrent adjuvant cancer therapy * Previous exposure to filgrastim, pegfilgrastim, or other G-CSF products in clinical development within 12 months prior to the administration of study drug * Active infection, receiving anti-infectives, or any underlying medical condition that would impair ability to receive protocol treatment * Prior bone marrow or stem cell transplant * Used any investigational drugs, biologics, or devices within 30 days prior to study treatment or plans to use any of these during the course of the study• Radiation therapy within 30 days prior to enrollment * Major surgery within 30 days prior to enrollment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Severe Neutropenia (DSN) in Cycle 1 | Day 1 and daily on Days 4-15 in Cycle 1 (each cycle = 21 days) | DSN was defined as the number of days of severe neutropenia (absolute neutrophil count \[ANC\] \<0.5×10\^9 per liter \[L\]) from the first occurrence of ANC below the threshold. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Depth of ANC Nadir in Cycle 1 | Day 1 and daily on Days 4-15 in Cycle 1 (each cycle = 21 days) | The depth of ANC Nadir was defined as the lowest ANC value after administration of study drug (SPI-2012 or pegfilgrastim) in Cycle 1. |
| Number of Participants With Febrile Neutropenia (FN) in Cycle 1 | Day 1 and daily on Days 4-15 in Cycle 1 (each cycle = 21 days) | FN was defined as an oral temperature \>38.3 degree Celsius (°C) (101.0 degrees Fahrenheit \[°F\]) or two consecutive readings of \>38.0°C (100.4°F) for 2 hours and ANC \<1.0×10\^9/L. |
| Duration of Severe Neutropenia (DSN) in Cycles 2, 3 and 4 | Days 1, 4, 7, 10, and 15 of Cycles 2, 3, and 4 (each cycle = 21 days) | DSN was defined as the number of days of severe neutropenia (ANC \<0.5×10\^9/L) from the first occurrence of ANC below the threshold. |
| Number of Participants With Neutropenic Complications in Cycle 1 | Day 1 and daily on Days 4-15 in Cycle 1 (each cycle = 21 days) | Neutropenic complications refer to hospitalizations due to neutropenic events and/or the use of anti-infectives due to neutropenia. |
| Time to Absolute Neutrophil Count (ANC) Recovery in Cycle 1 | Day 1 and daily on Days 4-15 in Cycle 1 (each cycle = 21 days) | Time to ANC recovery was defined as the time from chemotherapy administration until the participants ANC increased to \>=1.5×10\^9/L after the expected nadir. For participants with ANC value \>=1.5×10\^9/L at all times, time to ANC Recovery was assigned a value of 0. |
| Relative Dose Intensity (RDI) of TC Chemotherapy | Cycles 1, 2, 3 and 4 (each cycle = 21 days) | RDI was defined as the percentage of the planned dose of TC chemotherapy that each participant actually received during the study, and is expressed as the total dose received, divided by total dose planned multiplied by 100. The planned dose was defined as the dose that would be given if no doses were missed and/or no dose reductions were made for the number of cycles started. The total planned dose was the sum of planned doses over all cycles. |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs), and Death | Up to 4 cycles (each cycle = 21 days) plus a 12-month follow-up from the last dose (up to 15 months) | An adverse event (AE) is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product or study procedure, whether or not considered related to the medicinal product. A TEAE is any AE that occurred from the first dose of study treatment through 12 months after the last dose of study treatment or 35 (±5) days after date of participant early discontinuation. SAE is defined as any AE which meets any of the following criteria: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in a persistent or significant disability/incapacity, results in a congenital anomaly/birth defect, includes important medical events. |
| Number of Participants With Clinically Significant Laboratory Abnormalities | Up to 4 cycles (each cycle = 21 days) plus a 12-month follow-up from the last dose (up to 15 months) | The number of participants with clinically significant hematology (including basophils, basophils/leukocytes, eosinophils, eosinophils/leukocytes, hematocrit, hemoglobin, lymphocytes, lymphocytes/leukocytes, monocytes, monocytes/leukocytes, neutrophils, neutrophils/leukocytes, platelets, and white blood cells) and serum chemistry (including alanine aminotransferase \[ALT\], alkaline phosphatase \[ALP\], aspartate aminotransferase \[AST\], bilirubin, calcium, cholesterol, creatinine, potassium, sodium, and triglycerides) laboratory abnormalities were reported. Clinically significant findings in laboratory parameters were based on investigator's discretion according to Common Technical Criteria for Adverse Events (CTCAE) Version 4.03. |
| Number of Participants With Febrile Neutropenia in Cycles 2, 3 and 4 | Days 1, 4, 7, 10, and 15 of Cycles 2, 3, and 4 (each cycle = 21 days) | FN was defined as an oral temperature \>38.3°C (101.0°F) or two consecutive readings of \>38.0°C (100.4°F) for 2 hours and ANC \<1.0×10\^9/L. |
Countries
Canada, Hungary, India, Poland, South Korea, United States
Participant flow
Recruitment details
This study was conducted at 74 sites in the United States, Canada, Hungary, Poland, India, Korea from 10 May 2017 to 06 May 2019. The study was conducted in two periods: treatment period (first dose of TC until 35 (± 5) days after last dose of treatment) and safety follow-up period (End of Treatment Visit through 12 months after last dose of study treatment).
Pre-assignment details
A total of 237 participants were randomized into study, 118 participants in Arm 1 (SPI-2012 and TC) and 119 participants in Arm 2 (Pegfilgrastim and TC). 235 participants were treated, out of which 181 participants completed the study. All participants who received at least one dose of study drug (treatment period) entered the safety follow-up period.
Participants by arm
| Arm | Count |
|---|---|
| (Arm 1): SPI-2012 and TC At each cycle for 4 cycles, participants received SPI-2012 at a fixed dose of 13.2 mg/0.6 mL, \[3.6 mg granulocyte colony-stimulating factor {G-CSF}\] SC approximately 24-26 hours after receiving IV infusion of docetaxel 75 mg/m\^2 and cyclophosphamide 600 mg/m\^2 IV infusion per institute's standard of care. All participants were followed for 35 (±5) days after last study treatment or patient discontinuation and long-term safety follow-up continued for 12 months after last dose of study treatment. | 118 |
| (Arm 2): Pegfilgrastim and TC At each cycle for 4 cycles, participants received pegfilgrastim 6 mg (6 mg/0.6 mL G-CSF) SC approximately 24-26 hours after receiving IV infusion of docetaxel 75 mg/m\^2 and cyclophosphamide 600 mg/m\^2 IV infusion per institute's standard of care. All participants were followed for 35 (±5) days after last study treatment or patient discontinuation and long-term safety follow-up continued for 12 months after last dose of study treatment. | 119 |
| Total | 237 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 0 | 1 |
| Overall Study | Initiated Non-Protocol Therapy | 5 | 14 |
| Overall Study | Investigator Decision | 3 | 3 |
| Overall Study | Lost to Follow-up | 3 | 2 |
| Overall Study | Myeloid Growth Factors Treatment | 0 | 1 |
| Overall Study | Reason not specified | 2 | 2 |
| Overall Study | Sponsor decision | 0 | 2 |
| Overall Study | Withdrawal by Subject | 9 | 9 |
Baseline characteristics
| Characteristic | (Arm 1): SPI-2012 and TC | (Arm 2): Pegfilgrastim and TC | Total |
|---|---|---|---|
| Age, Continuous | 57.9 years STANDARD_DEVIATION 11.27 | 58.1 years STANDARD_DEVIATION 12.67 | 58.0 years STANDARD_DEVIATION 11.97 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 18 Participants | 15 Participants | 33 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 100 Participants | 104 Participants | 204 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 20 Participants | 16 Participants | 36 Participants |
| Race/Ethnicity, Customized Black or African American | 11 Participants | 7 Participants | 18 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White or Caucasian | 85 Participants | 96 Participants | 181 Participants |
| Sex: Female, Male Female | 118 Participants | 119 Participants | 237 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 117 | 1 / 118 | 0 / 117 | 0 / 118 |
| other Total, other adverse events | 115 / 117 | 116 / 118 | 33 / 117 | 48 / 118 |
| serious Total, serious adverse events | 12 / 117 | 19 / 118 | 2 / 117 | 4 / 118 |
Outcome results
Primary
Duration of Severe Neutropenia (DSN) in Cycle 1
DSN was defined as the number of days of severe neutropenia (absolute neutrophil count \[ANC\] \<0.5×10\^9 per liter \[L\]) from the first occurrence of ANC below the threshold.
Time frame: Day 1 and daily on Days 4-15 in Cycle 1 (each cycle = 21 days)
Population: ITT population included all participants who were randomized.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| (Arm 1): SPI-2012 and TC | Duration of Severe Neutropenia (DSN) in Cycle 1 | 0.31 Days | Standard Deviation 0.688 |
| (Arm 2): Pegfilgrastim and TC | Duration of Severe Neutropenia (DSN) in Cycle 1 | 0.39 Days | Standard Deviation 0.949 |
p-value: <0.000195% CI: [-0.292, 0.129]t-statistics
Secondary
Depth of ANC Nadir in Cycle 1
The depth of ANC Nadir was defined as the lowest ANC value after administration of study drug (SPI-2012 or pegfilgrastim) in Cycle 1.
Time frame: Day 1 and daily on Days 4-15 in Cycle 1 (each cycle = 21 days)
Population: ITT population included all participants who were randomized. Here 'N' (number of participants analyzed) signifies the number of participants evaluable for this outcome measure at the specified timepoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| (Arm 1): SPI-2012 and TC | Depth of ANC Nadir in Cycle 1 | 2.67 10^9 cells/L | Standard Deviation 3.504 |
| (Arm 2): Pegfilgrastim and TC | Depth of ANC Nadir in Cycle 1 | 2.06 10^9 cells/L | Standard Deviation 2.034 |
Secondary
Duration of Severe Neutropenia (DSN) in Cycles 2, 3 and 4
DSN was defined as the number of days of severe neutropenia (ANC \<0.5×10\^9/L) from the first occurrence of ANC below the threshold.
Time frame: Days 1, 4, 7, 10, and 15 of Cycles 2, 3, and 4 (each cycle = 21 days)
Population: ITT population included all participants who were randomized.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| (Arm 1): SPI-2012 and TC | Duration of Severe Neutropenia (DSN) in Cycles 2, 3 and 4 | Cycle 3 | 0.07 Days | Standard Deviation 0.252 |
| (Arm 1): SPI-2012 and TC | Duration of Severe Neutropenia (DSN) in Cycles 2, 3 and 4 | Cycle 2 | 0.08 Days | Standard Deviation 0.267 |
| (Arm 1): SPI-2012 and TC | Duration of Severe Neutropenia (DSN) in Cycles 2, 3 and 4 | Cycle 4 | 0.07 Days | Standard Deviation 0.252 |
| (Arm 2): Pegfilgrastim and TC | Duration of Severe Neutropenia (DSN) in Cycles 2, 3 and 4 | Cycle 3 | 0.07 Days | Standard Deviation 0.283 |
| (Arm 2): Pegfilgrastim and TC | Duration of Severe Neutropenia (DSN) in Cycles 2, 3 and 4 | Cycle 2 | 0.09 Days | Standard Deviation 0.432 |
| (Arm 2): Pegfilgrastim and TC | Duration of Severe Neutropenia (DSN) in Cycles 2, 3 and 4 | Cycle 4 | 0.08 Days | Standard Deviation 0.266 |
Secondary
Number of Participants With Clinically Significant Laboratory Abnormalities
The number of participants with clinically significant hematology (including basophils, basophils/leukocytes, eosinophils, eosinophils/leukocytes, hematocrit, hemoglobin, lymphocytes, lymphocytes/leukocytes, monocytes, monocytes/leukocytes, neutrophils, neutrophils/leukocytes, platelets, and white blood cells) and serum chemistry (including alanine aminotransferase \[ALT\], alkaline phosphatase \[ALP\], aspartate aminotransferase \[AST\], bilirubin, calcium, cholesterol, creatinine, potassium, sodium, and triglycerides) laboratory abnormalities were reported. Clinically significant findings in laboratory parameters were based on investigator's discretion according to Common Technical Criteria for Adverse Events (CTCAE) Version 4.03.
Time frame: Up to 4 cycles (each cycle = 21 days) plus a 12-month follow-up from the last dose (up to 15 months)
Population: SAF population included all participants who received at least one dose of any protocol-specified drug (TC or SPI-2012 or pegfilgrastim).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| (Arm 1): SPI-2012 and TC | Number of Participants With Clinically Significant Laboratory Abnormalities | Hematology: Lymphocytes | 0 Participants |
| (Arm 1): SPI-2012 and TC | Number of Participants With Clinically Significant Laboratory Abnormalities | Hematology: Basophils/Leukocytes | 0 Participants |
| (Arm 1): SPI-2012 and TC | Number of Participants With Clinically Significant Laboratory Abnormalities | Hematology: Eosinophils | 0 Participants |
| (Arm 1): SPI-2012 and TC | Number of Participants With Clinically Significant Laboratory Abnormalities | Hematology: Eosinophils/Leukocytes | 0 Participants |
| (Arm 1): SPI-2012 and TC | Number of Participants With Clinically Significant Laboratory Abnormalities | Hematology: Hematocrit | 4 Participants |
| (Arm 1): SPI-2012 and TC | Number of Participants With Clinically Significant Laboratory Abnormalities | Hematology: Hemoglobin | 6 Participants |
| (Arm 1): SPI-2012 and TC | Number of Participants With Clinically Significant Laboratory Abnormalities | Hematology: Basophils | 0 Participants |
| (Arm 1): SPI-2012 and TC | Number of Participants With Clinically Significant Laboratory Abnormalities | Hematology: Lymphocytes/Leukocytes | 6 Participants |
| (Arm 1): SPI-2012 and TC | Number of Participants With Clinically Significant Laboratory Abnormalities | Hematology: Monocytes | 0 Participants |
| (Arm 1): SPI-2012 and TC | Number of Participants With Clinically Significant Laboratory Abnormalities | Hematology: Monocytes/Leukocytes | 0 Participants |
| (Arm 1): SPI-2012 and TC | Number of Participants With Clinically Significant Laboratory Abnormalities | Hematology: Neutrophils | 17 Participants |
| (Arm 1): SPI-2012 and TC | Number of Participants With Clinically Significant Laboratory Abnormalities | Hematology: Neutrophils/Leukocytes | 12 Participants |
| (Arm 1): SPI-2012 and TC | Number of Participants With Clinically Significant Laboratory Abnormalities | Hematology: Platelets | 10 Participants |
| (Arm 1): SPI-2012 and TC | Number of Participants With Clinically Significant Laboratory Abnormalities | Hematology: White Blood Cells | 16 Participants |
| (Arm 1): SPI-2012 and TC | Number of Participants With Clinically Significant Laboratory Abnormalities | Chemistry: Alanine aminotransferase | 2 Participants |
| (Arm 1): SPI-2012 and TC | Number of Participants With Clinically Significant Laboratory Abnormalities | Chemistry: Alkaline phosphatase | 0 Participants |
| (Arm 1): SPI-2012 and TC | Number of Participants With Clinically Significant Laboratory Abnormalities | Chemistry: Aspartate aminotransferase | 1 Participants |
| (Arm 1): SPI-2012 and TC | Number of Participants With Clinically Significant Laboratory Abnormalities | Chemistry: Bilirubin | 0 Participants |
| (Arm 1): SPI-2012 and TC | Number of Participants With Clinically Significant Laboratory Abnormalities | Chemistry: Calcium | 1 Participants |
| (Arm 1): SPI-2012 and TC | Number of Participants With Clinically Significant Laboratory Abnormalities | Chemistry: Cholesterol | 0 Participants |
| (Arm 1): SPI-2012 and TC | Number of Participants With Clinically Significant Laboratory Abnormalities | Chemistry: Creatinine | 0 Participants |
| (Arm 1): SPI-2012 and TC | Number of Participants With Clinically Significant Laboratory Abnormalities | Chemistry: Potassium | 0 Participants |
| (Arm 1): SPI-2012 and TC | Number of Participants With Clinically Significant Laboratory Abnormalities | Chemistry: Sodium | 0 Participants |
| (Arm 1): SPI-2012 and TC | Number of Participants With Clinically Significant Laboratory Abnormalities | Chemistry: Triglycerides | 0 Participants |
| (Arm 2): Pegfilgrastim and TC | Number of Participants With Clinically Significant Laboratory Abnormalities | Chemistry: Sodium | 2 Participants |
| (Arm 2): Pegfilgrastim and TC | Number of Participants With Clinically Significant Laboratory Abnormalities | Hematology: Basophils | 0 Participants |
| (Arm 2): Pegfilgrastim and TC | Number of Participants With Clinically Significant Laboratory Abnormalities | Hematology: Platelets | 2 Participants |
| (Arm 2): Pegfilgrastim and TC | Number of Participants With Clinically Significant Laboratory Abnormalities | Hematology: Basophils/Leukocytes | 0 Participants |
| (Arm 2): Pegfilgrastim and TC | Number of Participants With Clinically Significant Laboratory Abnormalities | Chemistry: Calcium | 1 Participants |
| (Arm 2): Pegfilgrastim and TC | Number of Participants With Clinically Significant Laboratory Abnormalities | Hematology: Eosinophils | 0 Participants |
| (Arm 2): Pegfilgrastim and TC | Number of Participants With Clinically Significant Laboratory Abnormalities | Hematology: White Blood Cells | 18 Participants |
| (Arm 2): Pegfilgrastim and TC | Number of Participants With Clinically Significant Laboratory Abnormalities | Hematology: Eosinophils/Leukocytes | 0 Participants |
| (Arm 2): Pegfilgrastim and TC | Number of Participants With Clinically Significant Laboratory Abnormalities | Chemistry: Potassium | 1 Participants |
| (Arm 2): Pegfilgrastim and TC | Number of Participants With Clinically Significant Laboratory Abnormalities | Hematology: Hematocrit | 2 Participants |
| (Arm 2): Pegfilgrastim and TC | Number of Participants With Clinically Significant Laboratory Abnormalities | Chemistry: Alanine aminotransferase | 1 Participants |
| (Arm 2): Pegfilgrastim and TC | Number of Participants With Clinically Significant Laboratory Abnormalities | Hematology: Hemoglobin | 4 Participants |
| (Arm 2): Pegfilgrastim and TC | Number of Participants With Clinically Significant Laboratory Abnormalities | Chemistry: Cholesterol | 0 Participants |
| (Arm 2): Pegfilgrastim and TC | Number of Participants With Clinically Significant Laboratory Abnormalities | Hematology: Lymphocytes | 0 Participants |
| (Arm 2): Pegfilgrastim and TC | Number of Participants With Clinically Significant Laboratory Abnormalities | Chemistry: Alkaline phosphatase | 1 Participants |
| (Arm 2): Pegfilgrastim and TC | Number of Participants With Clinically Significant Laboratory Abnormalities | Hematology: Lymphocytes/Leukocytes | 13 Participants |
| (Arm 2): Pegfilgrastim and TC | Number of Participants With Clinically Significant Laboratory Abnormalities | Chemistry: Triglycerides | 0 Participants |
| (Arm 2): Pegfilgrastim and TC | Number of Participants With Clinically Significant Laboratory Abnormalities | Hematology: Monocytes | 0 Participants |
| (Arm 2): Pegfilgrastim and TC | Number of Participants With Clinically Significant Laboratory Abnormalities | Chemistry: Aspartate aminotransferase | 1 Participants |
| (Arm 2): Pegfilgrastim and TC | Number of Participants With Clinically Significant Laboratory Abnormalities | Hematology: Monocytes/Leukocytes | 0 Participants |
| (Arm 2): Pegfilgrastim and TC | Number of Participants With Clinically Significant Laboratory Abnormalities | Chemistry: Creatinine | 0 Participants |
| (Arm 2): Pegfilgrastim and TC | Number of Participants With Clinically Significant Laboratory Abnormalities | Hematology: Neutrophils | 23 Participants |
| (Arm 2): Pegfilgrastim and TC | Number of Participants With Clinically Significant Laboratory Abnormalities | Chemistry: Bilirubin | 0 Participants |
| (Arm 2): Pegfilgrastim and TC | Number of Participants With Clinically Significant Laboratory Abnormalities | Hematology: Neutrophils/Leukocytes | 9 Participants |
Secondary
Number of Participants With Febrile Neutropenia (FN) in Cycle 1
FN was defined as an oral temperature \>38.3 degree Celsius (°C) (101.0 degrees Fahrenheit \[°F\]) or two consecutive readings of \>38.0°C (100.4°F) for 2 hours and ANC \<1.0×10\^9/L.
Time frame: Day 1 and daily on Days 4-15 in Cycle 1 (each cycle = 21 days)
Population: ITT population included all participants who were randomized.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| (Arm 1): SPI-2012 and TC | Number of Participants With Febrile Neutropenia (FN) in Cycle 1 | 1 Participants |
| (Arm 2): Pegfilgrastim and TC | Number of Participants With Febrile Neutropenia (FN) in Cycle 1 | 4 Participants |
Secondary
Number of Participants With Febrile Neutropenia in Cycles 2, 3 and 4
FN was defined as an oral temperature \>38.3°C (101.0°F) or two consecutive readings of \>38.0°C (100.4°F) for 2 hours and ANC \<1.0×10\^9/L.
Time frame: Days 1, 4, 7, 10, and 15 of Cycles 2, 3, and 4 (each cycle = 21 days)
Population: ITT population included all participants who were randomized.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| (Arm 1): SPI-2012 and TC | Number of Participants With Febrile Neutropenia in Cycles 2, 3 and 4 | Cycle 2 | 0 Participants |
| (Arm 1): SPI-2012 and TC | Number of Participants With Febrile Neutropenia in Cycles 2, 3 and 4 | Cycle 3 | 0 Participants |
| (Arm 1): SPI-2012 and TC | Number of Participants With Febrile Neutropenia in Cycles 2, 3 and 4 | Cycle 4 | 0 Participants |
| (Arm 2): Pegfilgrastim and TC | Number of Participants With Febrile Neutropenia in Cycles 2, 3 and 4 | Cycle 2 | 2 Participants |
| (Arm 2): Pegfilgrastim and TC | Number of Participants With Febrile Neutropenia in Cycles 2, 3 and 4 | Cycle 3 | 0 Participants |
| (Arm 2): Pegfilgrastim and TC | Number of Participants With Febrile Neutropenia in Cycles 2, 3 and 4 | Cycle 4 | 0 Participants |
Secondary
Number of Participants With Neutropenic Complications in Cycle 1
Neutropenic complications refer to hospitalizations due to neutropenic events and/or the use of anti-infectives due to neutropenia.
Time frame: Day 1 and daily on Days 4-15 in Cycle 1 (each cycle = 21 days)
Population: ITT population included all participants who were randomized.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| (Arm 1): SPI-2012 and TC | Number of Participants With Neutropenic Complications in Cycle 1 | 1 Participants |
| (Arm 2): Pegfilgrastim and TC | Number of Participants With Neutropenic Complications in Cycle 1 | 5 Participants |
Secondary
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs), and Death
An adverse event (AE) is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product or study procedure, whether or not considered related to the medicinal product. A TEAE is any AE that occurred from the first dose of study treatment through 12 months after the last dose of study treatment or 35 (±5) days after date of participant early discontinuation. SAE is defined as any AE which meets any of the following criteria: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in a persistent or significant disability/incapacity, results in a congenital anomaly/birth defect, includes important medical events.
Time frame: Up to 4 cycles (each cycle = 21 days) plus a 12-month follow-up from the last dose (up to 15 months)
Population: SAF population included all participants who received at least one dose of any protocol-specified drug (TC or SPI-2012 or pegfilgrastim). Data was summarized and reported for Treatment and Follow-up period separately for both groups.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| (Arm 1): SPI-2012 and TC | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs), and Death | TEAEs | 115 Participants |
| (Arm 1): SPI-2012 and TC | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs), and Death | Death | 0 Participants |
| (Arm 1): SPI-2012 and TC | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs), and Death | SAEs | 12 Participants |
| (Arm 2): Pegfilgrastim and TC | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs), and Death | TEAEs | 116 Participants |
| (Arm 2): Pegfilgrastim and TC | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs), and Death | Death | 1 Participants |
| (Arm 2): Pegfilgrastim and TC | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs), and Death | SAEs | 19 Participants |
| (Arm 1): SPI-2012 and TC: Follow-up Period | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs), and Death | SAEs | 2 Participants |
| (Arm 1): SPI-2012 and TC: Follow-up Period | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs), and Death | TEAEs | 33 Participants |
| (Arm 1): SPI-2012 and TC: Follow-up Period | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs), and Death | Death | 0 Participants |
| Arm 2: Pegfilgrastim and TC: Follow-up Period | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs), and Death | TEAEs | 48 Participants |
| Arm 2: Pegfilgrastim and TC: Follow-up Period | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs), and Death | Death | 0 Participants |
| Arm 2: Pegfilgrastim and TC: Follow-up Period | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs), and Death | SAEs | 4 Participants |
Secondary
Relative Dose Intensity (RDI) of TC Chemotherapy
RDI was defined as the percentage of the planned dose of TC chemotherapy that each participant actually received during the study, and is expressed as the total dose received, divided by total dose planned multiplied by 100. The planned dose was defined as the dose that would be given if no doses were missed and/or no dose reductions were made for the number of cycles started. The total planned dose was the sum of planned doses over all cycles.
Time frame: Cycles 1, 2, 3 and 4 (each cycle = 21 days)
Population: Safety analysis (SAF) population included all participants who received at least one dose of any protocol-specified drug (TC or SPI-2012 or pegfilgrastim).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| (Arm 1): SPI-2012 and TC | Relative Dose Intensity (RDI) of TC Chemotherapy | Docetaxel | 96.9 Percentage of planned dose | Standard Deviation 7.7 |
| (Arm 1): SPI-2012 and TC | Relative Dose Intensity (RDI) of TC Chemotherapy | Cyclophosphamide | 98.4 Percentage of planned dose | Standard Deviation 5.27 |
| (Arm 2): Pegfilgrastim and TC | Relative Dose Intensity (RDI) of TC Chemotherapy | Docetaxel | 98.4 Percentage of planned dose | Standard Deviation 7.89 |
| (Arm 2): Pegfilgrastim and TC | Relative Dose Intensity (RDI) of TC Chemotherapy | Cyclophosphamide | 98.8 Percentage of planned dose | Standard Deviation 6.4 |
Secondary
Time to Absolute Neutrophil Count (ANC) Recovery in Cycle 1
Time to ANC recovery was defined as the time from chemotherapy administration until the participants ANC increased to \>=1.5×10\^9/L after the expected nadir. For participants with ANC value \>=1.5×10\^9/L at all times, time to ANC Recovery was assigned a value of 0.
Time frame: Day 1 and daily on Days 4-15 in Cycle 1 (each cycle = 21 days)
Population: ITT population included all participants who were randomized.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| (Arm 1): SPI-2012 and TC | Time to Absolute Neutrophil Count (ANC) Recovery in Cycle 1 | 3.49 Days | Standard Deviation 3.723 |
| (Arm 2): Pegfilgrastim and TC | Time to Absolute Neutrophil Count (ANC) Recovery in Cycle 1 | 3.35 Days | Standard Deviation 3.745 |