Phase 2 Study of SPI-2012 or Pegfilgrastim for the Manage... | NCT01724866

ID	Type	Description	Link
2013-003094-10	EudraCT Number

Label	Type	Description	Intervention Names
Arm 1: SPI-2012 45 µg/kg and Docetaxel + Cyclophosphamide (TC)	Experimental	Participants received SPI-2012 45 microgram/kilogram (µg/kg), subcutaneously (SC) once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows: Docetaxel 75 milligram/ square metre (mg/m^2) intravenous (IV) infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.	Drug: SPI-2012 Drug: Docetaxel Drug: Cyclophosphamide
Arm 2: SPI-2012 135 µg/kg and Docetaxel + Cyclophosphamide (TC)	Experimental	Participants received SPI-2012 135 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows: Docetaxel 75 mg/m^2 intravenous (IV) infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.	Drug: SPI-2012 Drug: Docetaxel Drug: Cyclophosphamide
Arm 3: SPI-2012 270 µg/kg and Docetaxel + Cyclophosphamide (TC)	Experimental	Participants received SPI-2012 270 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows: Docetaxel 75 mg/m^2 intravenous (IV) infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.	Drug: SPI-2012 Drug: Docetaxel Drug: Cyclophosphamide

Name	Type	Description	Arm Group Labels	Other Names
SPI-2012	Drug	SPI-2012 SC injection.	Arm 1: SPI-2012 45 µg/kg and Docetaxel + Cyclophosphamide (TC) Arm 2: SPI-2012 135 µg/kg and Docetaxel + Cyclophosphamide (TC)

Measure	Description	Time Frame
Duration of Severe Neutropenia (DSN) in Cycle 1	DSN was defined as the interval from the day of first observation of severe neutropenia (ANC <0.510^9/L, Grade 4 neutropenia per NCI CTCAE) to the first ANC recovery to => 2.010^9/L in Cycle 1.	Cycle 1 (each cycle was 21 days)

Measure	Description	Time Frame
Duration of DSN in Cycle 2	DSN was defined as the interval from the day of first observation of severe neutropenia (ANC <0.510^9/L, Grade 4 neutropenia per NCI CTCAE) to the first ANC recovery to => 2.010^9/L in Cycle 2.	Cycle 2 (each cycle was 21 days)
Duration of DSN in Cycle 3

Facility	Status	City	State	ZIP	Country	Contacts
Arizona Center for Cancer Care		Glendale	Arizona	85306	United States
Desert Springs Cancer Care

PubMed Identifier	Type	Citation	Retractions
29573207	Derived	Vacirca JL, Chan A, Mezei K, Adoo CS, Papai Z, McGregor K, Okera M, Horvath Z, Landherr L, Hanslik J, Hager SJ, Ibrahim EN, Rostom M, Bhat G, Choi MR, Reddy G, Tedesco KL, Agajanian R, Lang I, Schwartzberg LS. An open-label, dose-ranging study of Rolontis, a novel long-acting myeloid growth factor, in breast cancer. Cancer Med. 2018 May;7(5):1660-1669. doi: 10.1002/cam4.1388. Epub 2018 Mar 23.

ID	Title	Description
FG000	Arm 1: SPI-2012 45 µg/kg and Docetaxel + Cyclophosphamide (TC)	Participants received SPI-2012 45 µg/kg, subcutaneously (SC) once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows: Docetaxel 75 mg/m^2 intravenous (IV) infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Duration of Severe Neutropenia (DSN) in Cycle 1

DSN was defined as the interval from the day of first observation of severe neutropenia (ANC <0.5*10^9/L, Grade 4 neutropenia per NCI CTCAE) to the first ANC recovery to => 2.0*10^9/L in Cycle 1.

The Evaluable Population included all randomized participants who had received either SPI-2012 or pegfilgrastim and had completed Cycle 1.

Posted

Mean

Standard Deviation

days

Cycle 1 (each cycle was 21 days)

ID	Title	Description
OG000	Arm 1: SPI-2012 45 µg/kg and TC	Participants received SPI-2012 45 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows: Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.
OG001	Arm 2: SPI-2012 135 µg/kg and TC	Participants received SPI-2012 135 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows: Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.
OG002	Arm 3: SPI-2012 270 µg/kg and TC	Participants received SPI-2012 270 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows: Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.
OG003	Arm 4: Pegfilgrastim and TC	Participants received Pegfilgrastim 6 mg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows: Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.

Units	Counts
Participants	OG00039 OG00136 OG00236 OG003

Title

Denominators

Categories

Title	Measurements
	OG0001.03± 1.547 OG0010.44± 1.275 OG0020.03± 0.167 OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG003	A 2-sided 95% confidence interval (CI) for the difference in mean DSN between any 2 arms was calculated. Non-inferiority p-value was calculated as two times the proportion of treatment difference greater than 1 in the resampling.	Bootstrap method		0.296		Mean Difference (Final Values)	0.72			2-Sided	95	0.19	1.27					Non-Inferiority	Non-inferiority was demonstrated if the upper CI was < 1 day.

Secondary

Duration of DSN in Cycle 2

DSN was defined as the interval from the day of first observation of severe neutropenia (ANC <0.5*10^9/L, Grade 4 neutropenia per NCI CTCAE) to the first ANC recovery to => 2.0*10^9/L in Cycle 2.

Posted

Mean

Standard Deviation

days

Cycle 2 (each cycle was 21 days)

ID	Title	Description
OG000	Arm 1: SPI-2012 45 µg/kg and TC	Participants received SPI-2012 45 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows: Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.
OG001	Arm 2: SPI-2012 135 µg/kg and TC	Participants received SPI-2012 135 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows: Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.

Secondary

Duration of DSN in Cycle 3

DSN was defined as the interval from the day of first observation of severe neutropenia (ANC <0.5*10^9/L, Grade 4 neutropenia per NCI CTCAE) to the first ANC recovery to => 2.0*10^9/L in Cycle 3.

Posted

Mean

Standard Deviation

days

Cycle 3 (each cycle was 21 days)

ID	Title	Description
OG000	Arm 1: SPI-2012 45 µg/kg and TC	Participants received SPI-2012 45 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows: Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.
OG001	Arm 2: SPI-2012 135 µg/kg and TC	Participants received SPI-2012 135 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows: Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.

Secondary

Duration of DSN in Cycle 4

DSN was defined as the interval from the day of first observation of severe neutropenia (ANC <0.5*10^9/L, Grade 4 neutropenia per NCI CTCAE) to the first ANC recovery to => 2.0*10^9/L in Cycle 4.

Posted

Mean

Standard Deviation

days

Cycle 4 (each cycle was 21 days)

ID	Title	Description
OG000	Arm 1: SPI-2012 45 µg/kg and TC	Participants received SPI-2012 45 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows: Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.
OG001	Arm 2: SPI-2012 135 µg/kg and TC	Participants received SPI-2012 135 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows: Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.

Secondary

Time to ANC Recovery in Cycle 1

Time to ANC recovery was defined as the time from chemotherapy administration until ANC increased to ≥ 2×10^9/L after the expected nadir within Cycle 1. Time to ANC recovery was not calculated for participants whose ANC value didn't drop below 2 x10^9/L within Cycle 1.

Posted

Median

95% Confidence Interval

days

Cycle 1 (each cycle was 21 days)

ID	Title	Description
OG000	Arm 1: SPI-2012 45 µg/kg and TC	Participants received SPI-2012 45 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows: Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.
OG001	Arm 2: SPI-2012 135 µg/kg and TC	Participants received SPI-2012 135 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows: Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.

Secondary

Time to ANC Recovery in Cycle 2

Time to ANC recovery was defined as the time from chemotherapy administration until ANC increased to ≥2×10^9/L after the expected nadir within Cycle 2. Time to ANC recovery was not calculated for participants whose ANC value didn't drop below 2 x10^9/L within Cycle 2.

Posted

Median

95% Confidence Interval

days

Cycle 2 (each cycle was 21 days)

ID	Title	Description
OG000	Arm 1: SPI-2012 45 µg/kg and TC	Participants received SPI-2012 45 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows: Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.
OG001	Arm 2: SPI-2012 135 µg/kg and TC	Participants received SPI-2012 135 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows: Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.

Secondary

Time to ANC Recovery in Cycle 3

Time to ANC recovery was defined as the time from chemotherapy administration until ANC increased to ≥2×10^9/L after the expected nadir within Cycle 3. Time to ANC recovery was not calculated for participants whose ANC value didn't drop below 2 x10^9/L within Cycle 3.

Posted

Median

95% Confidence Interval

days

Cycle 3 (each cycle was 21 days)

ID	Title	Description
OG000	Arm 1: SPI-2012 45 µg/kg and TC	Participants received SPI-2012 45 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows: Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.
OG001	Arm 2: SPI-2012 135 µg/kg and TC	Participants received SPI-2012 135 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows: Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.

Secondary

Time to ANC Recovery in Cycle 4

Time to ANC recovery was defined as the time from chemotherapy administration until ANC increased to ≥2×10^9/L after the expected nadir within Cycle 4. Time to ANC recovery was not calculated for participants whose ANC value didn't drop below 2 x10^9/L within Cycle 4.

Posted

Median

95% Confidence Interval

days

Cycle 4 (each cycle was 21 days)

ID	Title	Description
OG000	Arm 1: SPI-2012 45 µg/kg and TC	Participants received SPI-2012 45 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows: Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.
OG001	Arm 2: SPI-2012 135 µg/kg and TC	Participants received SPI-2012 135 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows: Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.

Secondary

Absolute Neutrophil Count (ANC) Nadir Overtime in Cycle 1

Mean ANC nadir was defined as the mean of the lowest ANC value (*10^9/L) after administration of the study drug (SPI-2012 or pegfilgrastim) on any day in Days 1-3 of Cycle 1.

The Evaluable Population included all randomized participants who had received either SPI-2012 or pegfilgrastim and had completed Cycle 1.

Posted

Mean

Standard Deviation

10^9 ANC per liter

Cycle 1 (each cycle was 21 days)

ID	Title	Description
OG000	Arm 1: SPI-2012 45 µg/kg and TC	Participants received SPI-2012 45 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows: Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.
OG001	Arm 2: SPI-2012 135 µg/kg and TC	Participants received SPI-2012 135 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows: Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.
OG002

Secondary

Absolute ANC Nadir Overtime in Cycle 2

Mean ANC nadir was defined as the mean of the lowest ANC value (*10^9/L) after administration of the study drug (SPI-2012 or pegfilgrastim) on any day in Days 1-3 of Cycle 2.

Posted

Mean

Standard Deviation

10^9 ANC/L

Cycle 2 (each cycle was 21 days)

ID	Title	Description
OG000	Arm 1: SPI-2012 45 µg/kg and TC	Participants received SPI-2012 45 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows: Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.
OG001	Arm 2: SPI-2012 135 µg/kg and TC	Participants received SPI-2012 135 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows: Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.

Secondary

Absolute ANC Nadir Overtime in Cycle 3

Mean ANC nadir was defined as the mean of the lowest ANC value (*10^9/L) after administration of the study drug (SPI-2012 or pegfilgrastim) on any day in Days 1-3 of Cycle 3.

Posted

Mean

Standard Deviation

10^9 ANC/L

Cycle 3 (each cycle was 21 days)

ID	Title	Description
OG000	Arm 1: SPI-2012 45 µg/kg and TC	Participants received SPI-2012 45 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows: Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.
OG001	Arm 2: SPI-2012 135 µg/kg and TC	Participants received SPI-2012 135 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows: Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.

Secondary

Absolute ANC Nadir Overtime in Cycle 4

Mean ANC nadir was defined as the mean of the lowest ANC value (*10^9/L) after administration of the study drug (SPI-2012 or pegfilgrastim) on any day in Days 1-3 of Cycle 4.

Posted

Mean

Standard Deviation

10^9 ANC/L

Cycle 4 (each cycle was 21 days)

ID	Title	Description
OG000	Arm 1: SPI-2012 45 µg/kg and TC	Participants received SPI-2012 45 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows: Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.
OG001	Arm 2: SPI-2012 135 µg/kg and TC	Participants received SPI-2012 135 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows: Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.

Secondary

Depth of ANC Nadir in Cycle 1

Depth of ANC nadir was defined as the lowest Median ANC value (*10^9/L) after administration of the study drug (SPI-2012 or pegfilgrastim) on any day in Days 1-3 of Cycle 1.

The Evaluable Population included all randomized participants who had received either SPI-2012 or pegfilgrastim and had completed Cycle 1.

Posted

Median

Full Range

10^9 ANC/L

Cycle 1 (each cycle was 21 days)

ID	Title	Description
OG000	Arm 1: SPI-2012 45 µg/kg and TC	Participants received SPI-2012 45 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows: Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.
OG001	Arm 2: SPI-2012 135 µg/kg and TC	Participants received SPI-2012 135 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows: Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.
OG002	Arm 3: SPI-2012 270 µg/kg and TC

Secondary

Depth of ANC Nadir in Cycle 2

Depth of ANC nadir was defined as the lowest Median ANC value (*10^9/L) after administration of the study drug (SPI-2012 or pegfilgrastim) on any day in Days 1-3 of Cycle 2.

Posted

Median

95% Confidence Interval

10^9 ANC/L

Cycle 2 (each cycle was 21 days)

ID	Title	Description
OG000	Arm 1: SPI-2012 45 µg/kg and TC	Participants received SPI-2012 45 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows: Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.
OG001	Arm 2: SPI-2012 135 µg/kg and TC	Participants received SPI-2012 135 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows: Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.

Secondary

Depth of ANC Nadir in Cycle 3

Depth of ANC nadir was defined as the lowest Median ANC value (*10^9/L) after administration of the study drug (SPI-2012 or pegfilgrastim) on any day in Days 1-3 of Cycle 3.

Posted

Median

Full Range

10^9 ANC/L

Cycle 3 (each cycle was 21 days)

ID	Title	Description
OG000	Arm 1: SPI-2012 45 µg/kg and TC	Participants received SPI-2012 45 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows: Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.
OG001	Arm 2: SPI-2012 135 µg/kg and TC	Participants received SPI-2012 135 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows: Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.

Secondary

Depth of ANC Nadir in Cycle 4

Depth of ANC nadir was defined as the lowest Median ANC value (*10^9/L) after administration of the study drug (SPI-2012 or pegfilgrastim) on any day in Days 1-3 of Cycle 4.

Posted

Median

Full Range

10^9 ANC/L

Cycle 4 (each cycle was 21 days)

ID	Title	Description
OG000	Arm 1: SPI-2012 45 µg/kg and TC	Participants received SPI-2012 45 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows: Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.
OG001	Arm 2: SPI-2012 135 µg/kg and TC	Participants received SPI-2012 135 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows: Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.

Secondary

Time to ANC Nadir in Cycle 1

Time to ANC nadir was defined as the time from chemotherapy administration until the occurrence of the ANC nadir.

The Evaluable Population included all randomized participants who had received either SPI-2012 or pegfilgrastim and had completed Cycle 1.

Posted

Median

95% Confidence Interval

Days

Cycle 1 (each cycle was 21 days)

ID	Title	Description
OG000	Arm 1: SPI-2012 45 µg/kg and TC	Participants received SPI-2012 45 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows: Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.
OG001	Arm 2: SPI-2012 135 µg/kg and TC	Participants received SPI-2012 135 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows: Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.
OG002	Arm 3: SPI-2012 270 µg/kg and TC

Secondary

Time to ANC Nadir in Cycle 2

Time to ANC nadir was defined as the time from chemotherapy administration until the occurrence of the ANC nadir.

Posted

Median

95% Confidence Interval

days

Cycle 2 (each cycle was 21 days)

ID	Title	Description
OG000	Arm 1: SPI-2012 45 µg/kg and TC	Participants received SPI-2012 45 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows: Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.
OG001	Arm 2: SPI-2012 135 µg/kg and TC	Participants received SPI-2012 135 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows: Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.
OG002

Secondary

Time to ANC Nadir in Cycle 3

Time to ANC nadir was defined as the time from chemotherapy administration until the occurrence of the ANC nadir.

Posted

Median

95% Confidence Interval

days

Cycle 3 (each cycle was 21 days)

ID	Title	Description
OG000	Arm 1: SPI-2012 45 µg/kg and TC	Participants received SPI-2012 45 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows: Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.
OG001	Arm 2: SPI-2012 135 µg/kg and TC	Participants received SPI-2012 135 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows: Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.
OG002

Secondary

Time to ANC Nadir in Cycle 4

Time to ANC nadir was defined as the time from chemotherapy administration until the occurrence of the ANC nadir.

Posted

Median

95% Confidence Interval

days

Cycle 4 (each cycle was 21 days)

ID	Title	Description
OG000	Arm 1: SPI-2012 45 µg/kg and TC	Participants received SPI-2012 45 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows: Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.
OG001	Arm 2: SPI-2012 135 µg/kg and TC	Participants received SPI-2012 135 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows: Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.
OG002

Secondary

Percentage of Participants With Febrile Neutropenia (FN) Across All Cycles From Cycle 1 to Cycle 4

FN was defined as a temperature of more than 38.2 degree Celsius (°C) concurrent with an ANC greater than 0.5×10^9/L..

The Evaluable Population included all randomized participants who had received either SPI-2012 or pegfilgrastim and had completed Cycle 1.

Posted

Number

percentage of participants

Cycle 1 to Cycle 4 (each cycle was 21 days)

ID	Title	Description
OG000	Arm 1: SPI-2012 45 µg/kg and TC	Participants received SPI-2012 45 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows: Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.
OG001	Arm 2: SPI-2012 135 µg/kg and TC	Participants received SPI-2012 135 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows: Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.
OG002	Arm 3: SPI-2012 270 µg/kg and TC

Secondary

Number of Participants With Worst Grade Adverse Events (AEs), Deaths, Other Serious Adverse Events (SAEs), and Other AEs Leading to Discontinuation From Study Therapy, and Worst Grade Laboratory Abnormalities

An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. An SAE was an AE resulting in any of following outcomes or deemed significant for any other reason: death, initial or prolonged inpatient hospitalization, life-threatening experience (immediate risk of dying), persistent or significant disability or incapacity, congenital anomaly. Participants with SAE other than death were reported.AE and Laboratory Abnormalities ("Hematology and Chemistry") were collected and graded as per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03, where Grade 3 refers to severe or medically significant but not immediately life threatening; hospitalization or prolongation of hospitalization indicated and Grade 4 refers to life-threatening consequences; urgent intervention indicated.

The Safety Population included all randomized participants who had received at least one dose of any protocol specified drug (i.e., docetaxel, cyclophosphamide, SPI-2012 or pegfilgrastim).

Posted

Count of Participants

Participants

From the first dose up to 30 days post last dose of study drug (up to 4 months)

ID	Title	Description
OG000	Arm 1: SPI-2012 45 µg/kg and TC	Participants received SPI-2012 45 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows: Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.

Secondary

Percentage of Participants With Hospitalization Across All Cycles From Cycle 1 to Cycle 4

The Evaluable Population included all randomized participants who had received either SPI-2012 or pegfilgrastim and had completed Cycle 1.

Posted

Number

percentage of participants

All cycles from Cycle 1 to Cycle 4 (each cycle was 21 days)

ID	Title	Description
OG000	Arm 1: SPI-2012 45 µg/kg and TC	Participants received SPI-2012 45 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows: Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.
OG001	Arm 2: SPI-2012 135 µg/kg and TC	Participants received SPI-2012 135 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows: Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.
OG002	Arm 3: SPI-2012 270 µg/kg and TC	Participants received SPI-2012 270 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows: Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.

Secondary

Number of Participants With Positive Antibodies for SPI-2012

Serum samples were to be tested in a screening assay for antibodies binding to SPI-2012 using a validated enzyme-linked immunosorbent assay (ELISA). Any serum samples positive for the antibody were to be tested in a confirmatory competitive inhibition assay using two antigens, SPI-2012 or granulocyte colony-stimulating factor (G-CSF), to confirm the presence of antibodies binding to SPI-2012 and to identify samples that were positive for antibodies binding to G-CSF.

The Evaluable Population included all randomized participants who had received either SPI-2012 or pegfilgrastim and had completed Cycle 1. Overall number of participants analyzed included participants who were treated with SPI-2012 and had post-treatment samples collected, and excluded participants who tested positive before being treated with SPI-2012. Data was collected and analyzed only for the "SPI-2012" reporting arms as per the planned analysis.

Posted

Count of Participants

Participants

Up to the end of the study (Approximately 3.5 months)

ID	Title	Description
OG000	Arm 1: SPI-2012 45 µg/kg and TC	Participants received SPI-2012 45 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows: Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.
OG001	Arm 2: SPI-2012 135 µg/kg and TC

Secondary

Time to Reach Maximum Concentration of SPI-2012 (Tmax)

Blood samples were collected at specific time points to determine the serum concentrations of SPI-2012 and to derive pharmacokinetic (PK) parameters.

The PK Population included subset of participants who had received at least one dose of SPI-2012 in Arms 1 to 3 and have sufficient number of blood samples. Overall number of participants analyzed signifies the number of participants who were evaluable for this outcome measure.

Posted

Median

Full Range

hours (hrs)

Pre-dose and at 1, 3, 6, 8, 10, 24, 48, 72, 144, 192, and 312 hours post-dose in Cycle 1 (each cycle was 21 days)

ID	Title	Description
OG000	Arm 1: SPI-2012 45 µg/kg and TC	Participants received SPI-2012 45 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows: Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.
OG001	Arm 2: SPI-2012 135 µg/kg and TC	Participants received SPI-2012 135 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows: Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.

Secondary

Maximum Concentration of SPI-2012 (Cmax)

Blood samples were collected at specific time points to determine the serum concentrations of SPI-2012 and to derive PK parameters.

The PK Population included subset of participants who had received at least one dose of SPI-2012 in Arms 1 to 3 and had sufficient number of blood samples. Overall number of participants analyzed signifies the number of participants who were evaluable for this outcome measure.

Posted

Mean

Standard Deviation

nanograms per milliliter (ng/mL)

Pre-dose and at 1, 3, 6, 8, 10, 24, 48, 72, 144, 192, and 312 hours post-dose in Cycle 1 (each cycle was 21 days)

ID	Title	Description
OG000	Arm 1: SPI-2012 45 µg/kg and TC	Participants received SPI-2012 45 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows: Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.
OG001	Arm 2: SPI-2012 135 µg/kg and TC	Participants received SPI-2012 135 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows: Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.

Secondary

Area Under the Serum Concentration-Time Curve From Time Zero to 312 Hours Post-Dose (AUC0-312)

AUC(0-312) is the area under the serum concentration-time curve from time zero to 312 hour post dose calculated by the linear trapezoidal rule. Blood samples were collected at specific time points to determine the serum concentrations of SPI-2012 and to derive PK parameters.

The PK Population included subset of participants who had received at least one dose of SPI-2012 in Arms 1 to 3 and have sufficient number of blood samples to estimate AUC. The AUC0-312 was not calculated for the 45 µg/kg dose due to insufficient data in the serum concentration profiles. Overall number of participants analyzed signifies the number of participants who were evaluable for this outcome measure.

Posted

Mean

Standard Deviation

nanogram*hour per milliliter (ng*hr/mL)

Pre-dose and at 1, 3, 6, 8, 10, 24, 48, 72, 144, 192, and 312 hours post-dose in Cycle 1 (each cycle was 21 days)

ID	Title	Description
OG000	Arm 1: SPI-2012 45 µg/kg and TC	Participants received SPI-2012 45 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows: Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.
OG001	Arm 2: SPI-2012 135 µg/kg and TC	Participants received SPI-2012 135 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows: Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.

Secondary

Half-life of SPI-2012 (t1/2)

t1/2 data were calculated and reported as harmonic mean and pseudo standard deviation (SD). Blood samples were collected at specific time points to determine the serum concentrations of SPI-2012 and to derive PK parameters.

The PK Population included subset of participants who had received at least one dose of SPI-2012 in Arms 1 to 3 and had sufficient number of blood samples to estimate AUC. The t1/2 was not calculated for the 45 µg/kg arm because there were insufficient data in terminal phase of serum concentration profiles. Overall number of participants analyzed signifies the number of participants who were evaluable for this outcome measure.

Posted

Mean

Standard Deviation

hrs

Pre-dose and at 1, 3, 6, 8, 10, 24, 48, 72, 144, 192, and 312 hours post-dose in Cycle 1 (each cycle was 21 days)

ID	Title	Description
OG000	Arm 1: SPI-2012 45 µg/kg and TC	Participants received SPI-2012 45 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows: Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.
OG001	Arm 2: SPI-2012 135 µg/kg and TC	Participants received SPI-2012 135 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows: Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA (13.1)	Systematic Assessment	EG0002 affected39 at risk EG0011 affected37 at risk EG0021 affected36 at risk EG0031 affected36 at risk
Angina pectoris	Cardiac disorders	MedDRA (13.1)	Systematic Assessment	EG0001 affected39 at risk EG0010 affected37 at risk EG0020 affected36 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA (13.1)	Systematic Assessment	EG0000 affected39 at risk EG0010 affected37 at risk EG0020 affected36 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA (13.1)	Systematic Assessment	EG0001 affected39 at risk EG0010 affected37 at risk EG0020 affected36 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA (13.1)	Systematic Assessment	EG0001 affected39 at risk EG0010 affected37 at risk EG0020 affected36 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA (13.1)	Systematic Assessment	EG0001 affected39 at risk EG0010 affected37 at risk EG0020 affected36 at risk EG003
Non-cardiac chest pain	General disorders	MedDRA (13.1)	Systematic Assessment	EG0000 affected39 at risk EG0011 affected37 at risk EG0020 affected36 at risk EG003
Pyrexia	General disorders	MedDRA (13.1)	Systematic Assessment	EG0000 affected39 at risk EG0010 affected37 at risk EG0020 affected36 at risk EG003
Bacteraemia	Infections and infestations	MedDRA (13.1)	Systematic Assessment	EG0001 affected39 at risk EG0010 affected37 at risk EG0020 affected36 at risk EG003
Diverticulitis	Infections and infestations	MedDRA (13.1)	Systematic Assessment	EG0001 affected39 at risk EG0010 affected37 at risk EG0021 affected36 at risk EG003
Gastritis viral	Infections and infestations	MedDRA (13.1)	Systematic Assessment	EG0000 affected39 at risk EG0011 affected37 at risk EG0020 affected36 at risk EG003
Pneumonia	Infections and infestations	MedDRA (13.1)	Systematic Assessment	EG0000 affected39 at risk EG0011 affected37 at risk EG0020 affected36 at risk EG003
Road traffic accident	Injury, poisoning and procedural complications	MedDRA (13.1)	Systematic Assessment	EG0001 affected39 at risk EG0010 affected37 at risk EG0020 affected36 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA (13.1)	Systematic Assessment	EG0001 affected39 at risk EG0010 affected37 at risk EG0020 affected36 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (13.1)	Systematic Assessment	EG0000 affected39 at risk EG0010 affected37 at risk EG0020 affected36 at risk EG003
Renal failure acute	Renal and urinary disorders	MedDRA (13.1)	Systematic Assessment	EG0001 affected39 at risk EG0010 affected37 at risk EG0020 affected36 at risk EG003
Vaginal haemorrhage	Reproductive system and breast disorders	MedDRA (13.1)	Systematic Assessment	EG0000 affected39 at risk EG0010 affected37 at risk EG0020 affected36 at risk EG003
Urticaria	Skin and subcutaneous tissue disorders	MedDRA (13.1)	Systematic Assessment	EG0000 affected39 at risk EG0010 affected37 at risk EG0020 affected36 at risk EG003
Cellulitis	Infections and infestations	MedDRA (13.1)	Systematic Assessment	EG0000 affected39 at risk EG0010 affected37 at risk EG0020 affected36 at risk EG003

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhoea	Gastrointestinal disorders	MedDRA (13.1)	Systematic Assessment	EG00017 affected39 at risk EG0017 affected37 at risk EG00214 affected36 at risk EG00315 affected36 at risk
Nausea	Gastrointestinal disorders	MedDRA (13.1)	Systematic Assessment	EG00019 affected39 at risk EG00112 affected37 at risk EG00215 affected36 at risk EG003
Asthenia	General disorders	MedDRA (13.1)	Systematic Assessment	EG0005 affected39 at risk EG0012 affected37 at risk EG0025 affected36 at risk EG003
Fatigue	General disorders	MedDRA (13.1)	Systematic Assessment	EG00024 affected39 at risk EG00111 affected37 at risk EG00219 affected36 at risk EG003
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA (13.1)	Systematic Assessment	EG0009 affected39 at risk EG00110 affected37 at risk EG00212 affected36 at risk EG003
Headache	Nervous system disorders	MedDRA (13.1)	Systematic Assessment	EG00012 affected39 at risk EG0015 affected37 at risk EG0028 affected36 at risk EG003
Alopecia	Skin and subcutaneous tissue disorders	MedDRA (13.1)	Systematic Assessment	EG00021 affected39 at risk EG00118 affected37 at risk EG00212 affected36 at risk EG003
Insomnia	Psychiatric disorders	MedDRA (13.1)	Systematic Assessment	EG0003 affected39 at risk EG0015 affected37 at risk EG0025 affected36 at risk EG003

ID	Term
D000380	Agranulocytosis
D007970	Leukopenia
D000095542	Cytopenia
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases
D007960	Leukocyte Disorders

ID	Term
D043823	Taxoids
D043822	Cyclodecanes
D003516	Cycloparaffins
D006840	Hydrocarbons, Alicyclic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D009930	Organic Chemicals
D004224	Diterpenes
D013729	Terpenes
D010752	Phosphoramide Mustards
D009588	Nitrogen Mustard Compounds
D009150	Mustard Compounds
D006846	Hydrocarbons, Halogenated
D063088	Phosphoramides
D009943	Organophosphorus Compounds

ID	Title	Description
BG000	Arm 1: SPI-2012 45 µg/kg and TC	Participants received SPI-2012 45 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows: Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.
BG001	Arm 2: SPI-2012 135 µg/kg and TC	Participants received SPI-2012 135 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows: Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.
BG002	Arm 3: SPI-2012 270 µg/kg and TC	Participants received SPI-2012 270 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows: Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.
BG003	Arm 4: Pegfilgrastim and TC	Participants received Pegfilgrastim 6 mg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows: Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.
BG004	Total	Total of all reporting groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Arm 1: SPI-2012 45 µg/kg and TC	Participants received SPI-2012 45 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows: Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.	39	5	39	36	39
EG001	Arm 2: SPI-2012 135 µg/kg and TC	Participants received SPI-2012 135 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows: Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.	37	4	37	33	37
EG002	Arm 3: SPI-2012 270 µg/kg and TC	Participants received SPI-2012 270 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows: Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.	36	2	36	33	36
EG003	Arm 4: Pegfilgrastim and TC	Participants received Pegfilgrastim 6 mg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows: Docetaxel 75 mg/m^2 IV infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes.	36	8	36	35	36

ID	Term
C583329	eflapegrastim
C455861	pegfilgrastim
D000077143	Docetaxel
D003520	Cyclophosphamide