SPI-2012 vs Pegfilgrastim in Management of Neutropenia in Breast Cancer Participants With Docetaxel and Cyclophosphamide

• Sponsor: Spectrum Pharmaceuticals, Inc (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02953340
• Collaborator: (none)
• Enrollment: 237
• Locations: 74
• Arms: 2
• Actual Duration (Months): 23.9
• Patients Per Site: 3.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Neutropenia; Breast Cancer	Drug: SPI-2012; Drug: Pegfilgrastim; Drug: Docetaxel; Drug: Cyclophosphamide	Phase 3

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 237 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Randomized, OpEn-Label, Active-ContrOl Trial of SPI-2012 (Eflapegrastim) Versus Pegfilgrastim in the Management of Chemotherapy-Induced Neutropenia in Early-Stage BReast Cancer Patients Receiving Docetaxel and Cyclophosphamide (TC) (RECOVER)
• Actual Study Start Date: May 10, 2017
• Actual Primary Completion Date: Jun 8, 2018
• Actual Study Completion Date: May 6, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: (Arm 1): SPI-2012 and TC At each cycle for 4 cycles, participants received SPI-2012 at a fixed dose of 13.2 milligrams (mg)/0.6 milliliter (mL), [3.6 mg granulocyte colony-stimulating factor {G-CSF}] subcutaneously (SC) approximately 24-26 hours after receiving intravenous (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.	Drug: SPI-2012; Supplied in prefilled single-use syringes for subcutaneous injection, administered on Day 2 of each cycle; Other Names: HM10460A Rolontis® Eflapegrastim ; Drug: Docetaxel; 75mg/m^2 IV infusion administered on Day 1 of each cycle; Other Names: Taxotere ; Drug: Cyclophosphamide; 600mg/m^2 IV infusion administered on Day 1 of each cycle; Other Names: Cytoxan
Experimental: (Arm 2): Pegfilgrastim and TC At each cycle for 4 cycles, participants received pegfilgrastim 6 mg (6 mg/0.6 mL GCSF) 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.	Drug: Pegfilgrastim; Subcutaneous injection administered on Day 2 of each cycle.; Other Names: Neulasta® ; Drug: Docetaxel; 75mg/m^2 IV infusion administered on Day 1 of each cycle; Other Names: Taxotere ; Drug: Cyclophosphamide; 600mg/m^2 IV infusion administered on Day 1 of each cycle; Other Names: Cytoxan

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.

7. 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.

8. 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.

9. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	ACRC/ Arizona Clinical Research Center Inc.	Tucson	Arizona	United States	85715
2	Yuma Regional Cancer Center	Yuma	Arizona	United States	85364
3	Genesis Cancer Center	Hot Springs	Arkansas	United States	71913
4	NEA Baptist Clinic | Fowler Family Center for Cancer Care	Jonesboro	Arkansas	United States	72401
5	Pacific Cancer Medical Center, Inc.	Anaheim	California	United States	92801
6	Compassionate Care Research Group, Inc.	Fountain Valley	California	United States	92708
7	California Cancer Associates for Research and Excellence Inc.	Fresno	California	United States	93720
8	Pacific Shores Medical Group	Long Beach	California	United States	90813
9	Los Angeles Hematology Oncology Medical Group	Los Angeles	California	United States	90017
10	Desert Regional Medical Center	Palm Springs	California	United States	92262
11	Emad Ibrahim, MD, INC.	Redlands	California	United States	92373
12	Innovative Clinical Research Institute/ The Oncology Institute of Hope and Innovation	Whittier	California	United States	90603
13	Denver Health & Hospital Authority	Denver	Colorado	United States	80204
14	Pasco Pinellas Cancer Center	Holiday	Florida	United States	34691
15	Lakes Research, LLC	Miami Lakes	Florida	United States	33014
16	Mid-Florida Hematology and Oncology Centers	Orange City	Florida	United States	32763
17	Millennium Oncology	Pembroke Pines	Florida	United States	33024
18	BRCR Medical Center Inc	Plantation	Florida	United States	33324
19	Pinellas Hematology and Oncology	Saint Petersburg	Florida	United States	33709
20	Bond & Steele Clinic, PA.	Winter Haven	Florida	United States	33880
21	John B. Amos Cancer Center	Columbus	Georgia	United States	31904
22	Cancer Center of Middle Georgia	Dublin	Georgia	United States	31021
23	Dwight D. Eisenhower Army Medical Center	Fort Gordon	Georgia	United States	30905
24	Saint Alphonsus Regional Medical Center	Boise	Idaho	United States	83706
25	Oncology Specialists, SC	Park Ridge	Illinois	United States	60068
26	FPN Oncology and Hematology Specialists	Indianapolis	Indiana	United States	46237
27	Commonwealth Hematology-Oncology, PSC	Danville	Kentucky	United States	40422
28	Pontchartrain Cancer Center	Covington	Louisiana	United States	70433
29	Quest Research Institute	Royal Oak	Michigan	United States	48073
30	Coborn Cancer Center	Saint Cloud	Minnesota	United States	56303
31	Hattiesburg Clinic Hematology/Oncology	Hattiesburg	Mississippi	United States	39401
32	Freeman Health Systems	Joplin	Missouri	United States	64804
33	St. Vincent Frontier Cancer Center	Billings	Montana	United States	59102
34	CHI Health St Francis, St Francis Cancer Treatment Center	Grand Island	Nebraska	United States	68803
35	Waverly Hematology Oncology	Cary	North Carolina	United States	27518
36	Gaston Hematology & Oncology Associates, PC	Gastonia	North Carolina	United States	28054
37	Aultman Hospital	Canton	Ohio	United States	44710
38	The Christ Hospital Cancer Center	Cincinnati	Ohio	United States	45219
39	St. Elizabeth Youngstown Hospital JACBCC/Oncology/ Mercy Health Youngstown LLC	Youngstown	Ohio	United States	44501
40	Carolina Blood and Cancer Care Associates	Rock Hill	South Carolina	United States	29732
41	The West Clinic, PC, d/b/a West Cancer Center	Germantown	Tennessee	United States	38138
42	CHI St Joseph Health Cancer Center	Bryan	Texas	United States	77802
43	Envision Cancer Center, LLC	Laredo	Texas	United States	78041
44	Texas Oncology, PA- McAllen South 2nd Street	McAllen	Texas	United States	78503
45	HOPE Cancer Center of East Texas	Tyler	Texas	United States	75701
46	Delta Hematology/Oncology Associates	Portsmouth	Virginia	United States	23704
47	Providence Regional Center Partnership	Everett	Washington	United States	98201
48	Northwest Medical Specialties, PLLC	Tacoma	Washington	United States	98405
49	West Virginia University	Morgantown	West Virginia	United States	26506
50	CISSS de la Montérégie-Centre	Longueuil	Quebec	Canada	J4V 2H1
51	Jewish General Hospital	Montreal	Quebec	Canada	H3T 1E2
52	Magyar Honvedseg Egeszsegugyi Kozpont, Onkologiai Osztaly	Budapest		Hungary	1062
53	Szent Imre Egyetemi Oktatokorhaz, Klinikai Onkologiai Osztaly	Budapest		Hungary	1115
54	Orszagos Onkologiai Intezet, ""B"" Belgyogyaszati Onkologiai Osztaly	Budapest		Hungary	1122
55	Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi Okato Korhaz, Klinikai Onkologiai es Sugarterapias Centrum	Miskolc		Hungary	3526
56	Szabolcs-Szatmar-Bereg Megyei Korhazak, Egyetemi Oktato Korhaz, Onkoradiologiai Osztaly	Nyíregyháza		Hungary	4400
57	Tolna Megyei Balassa Janos Korhaz, Klinikai Onkologiai Osztaly	Szekszard		Hungary	7100
58	KEM Hospital Research Centre	Pune	Maharashtra	India	411011
59	Christian Medical College	Vellore	Tamil Nadu	India	632004
60	Samsung Medical Center	Irwon-ro	Gangnam-gu Seoul	Korea, Republic of	06351
61	Wonju Severance Christian Hospital	Ilsan-ro	Gangwon-do	Korea, Republic of	26426
62	National Cancer Center	IIsan-ro	Gyeonggi-do	Korea, Republic of	10408
63	Cha Bundang Medical Center	Yatap-ro	Gyeonggi-do	Korea, Republic of	13496
64	Seoul National University Hospital	Daehwa-ro	Jongno-gu Seoul	Korea, Republic of	03080
65	Inha University Hospital	Inhang-ro	Jung-guIncheon	Korea, Republic of	22332
66	Korea University Anam Hospital	Inchon-ro	Seongbuk-guSeoul	Korea, Republic of	02841
67	Severance Hospital	Yonsei-ro	Seoul	Korea, Republic of	03722
68	BIALOSTOCKIE CENTRUM ONKOLOGII im. Marii Sklodowskiej-Curie Oddzial Onkologii Klinicznej im. Ewy Pileckiej z Pododdzialem Chemioterapii dziennej	Bialystok		Poland	15-027
69	Regionalny Szpital Specjalistyczny im. dr Wladyslawa Bieganskiego Oddział Onkologii Klinicznej	Grudziadz		Poland	86-300
70	Instytut Centrum Zdrowia Matki Polki Klinika Chirurgii Onkologicznej i Chorob Piersi z Pododdzialem Onkologii Klinicznej	Lodz		Poland	93-338
71	Pracownia Leku Cytotoksycznego Szpitala Klinicznego Przemienienia Panskiego UM im. Karola Marcinkowskiego w Poznaniu	Poznan		Poland	60-569
72	Szpital Rejonowy im. Dr. Jozefa Rostka w Raciborzu Dzienny Oddzial Chemioterapii	Racibórz		Poland	47-400
73	MrukMed. Lekarz Beata Madej Mruk i Partner. Spolka Partnerska Oddzial nr 1 w Rzeszowie	Rzeszow		Poland	35-021
74	Zachodniopomorskie Centrum Onkologii Osrodek Innowacyjnosci, Rozwoju i Badan Klinicznych	Szczecin		Poland	71-730

Sponsors and Collaborators

• Spectrum Pharmaceuticals, Inc

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Jul 28, 2017
• Statistical Analysis Plan - Aug 6, 2018

More Information

Publications

None provided.

• Responsible Party: Spectrum Pharmaceuticals, Inc
• ClinicalTrials.gov Identifier: NCT02953340
• Other Study ID Numbers: SPI-GCF-302; 2016-003469-24
• First Posted: Nov 2, 2016
• Last Update Posted: Mar 2, 2022
• Last Verified: Jan 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Spectrum Pharmaceuticals, Inc: Neutropenia; Breast Cancer; Long-acting Granulocyte Colony Stimulating Factor; Early Stage Breast Cancer; Docetaxel + Cyclophosphamide (TC) chemotherapy
• Additional relevant MeSH terms: Breast Neoplasms; Neutropenia; Cyclophosphamide; Docetaxel

Study Results

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 Detail	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.

Arm/Group Title	(Arm 1): SPI-2012 and TC	(Arm 2): Pegfilgrastim and TC
Arm/Group Description	At each cycle for 4 cycles, participants received SPI-2012 at a fixed dose of 13.2 milligrams (mg)/0.6 milliliter (mL), [3.6 mg granulocyte colony-stimulating factor {G-CSF}] subcutaneously (SC) approximately 24-26 hours after receiving intravenous (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.	At each cycle for 4 cycles, participants received pegfilgrastim 6 mg (6 mg/0.6 mL GCSF) 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.
Period Title: Overall Study
STARTED	118	119
Safety Population	117	118
Entered Safety Follow-up Period	117	118
COMPLETED	96	85
NOT COMPLETED	22	34

Baseline Characteristics

Arm/Group Title	(Arm 1): SPI-2012 and TC	(Arm 2): Pegfilgrastim and TC	Total
Arm/Group Description	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.	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.	Total of all reporting groups
Overall Participants	118	119	237
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.9 (11.27)	58.1 (12.67)	58.0 (11.97)
Sex: Female, Male (Count of Participants)
Female	118 100%	119 100%	237 100%
Male	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	18 15.3%	15 12.6%	33 13.9%
Not Hispanic or Latino	100 84.7%	104 87.4%	204 86.1%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
White or Caucasian	85 72%	96 80.7%	181 76.4%
Black or African American	11 9.3%	7 5.9%	18 7.6%
Asian	20 16.9%	16 13.4%	36 15.2%
American Indian or Alaska Native	1 0.8%	0 0%	1 0.4%
Other	1 0.8%	0 0%	1 0.4%

Outcome Measures

1. Primary Outcome

Title	Duration of Severe Neutropenia (DSN) in Cycle 1
Description	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)

Outcome Measure Data

Analysis Population Description

ITT population included all participants who were randomized.

Arm/Group Title	(Arm 1): SPI-2012 and TC	(Arm 2): Pegfilgrastim and TC
Arm/Group Description	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.	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.
Measure Participants	118	119
Mean (Standard Deviation) [Days]	0.31 (0.688)	0.39 (0.949)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	(Arm 1): SPI-2012 and TC, (Arm 2): Pegfilgrastim and TC
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	The study used non inferiority margin of 0.62 days for the above comparison. The non-inferiority of SPI-2012 to Pegfilgrastim was declared if the upper bound of 95% confidence interval (CI) of the difference in mean DSN between the treatment arms was <0.62 days.
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	t-statistics
	Comments	The p-values are based on the calculated t-statistics from the bootstrapped sample mean and standard deviation.
Method of Estimation	Estimation Parameter	Mean difference
	Estimated Value	-0.074
	Confidence Interval	(2-Sided) 95%; -0.292 to 0.129
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Time to Absolute Neutrophil Count (ANC) Recovery in Cycle 1
Description	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)

Outcome Measure Data

Analysis Population Description

ITT population included all participants who were randomized.

Arm/Group Title	(Arm 1): SPI-2012 and TC	(Arm 2): Pegfilgrastim and TC
Arm/Group Description	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.	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.
Measure Participants	118	119
Mean (Standard Deviation) [Days]	3.49 (3.723)	3.35 (3.745)

3. Secondary Outcome

Title	Depth of ANC Nadir in Cycle 1
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	(Arm 1): SPI-2012 and TC	(Arm 2): Pegfilgrastim and TC
Arm/Group Description	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.	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.
Measure Participants	115	116
Mean (Standard Deviation) [10^9 cells/L]	2.67 (3.504)	2.06 (2.034)

4. Secondary Outcome

Title	Number of Participants With Febrile Neutropenia (FN) in Cycle 1
Description	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)

Outcome Measure Data

Analysis Population Description

ITT population included all participants who were randomized.

Arm/Group Title	(Arm 1): SPI-2012 and TC	(Arm 2): Pegfilgrastim and TC
Arm/Group Description	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.	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.
Measure Participants	118	119
Count of Participants [Participants]	1 0.8%	4 3.4%

5. Secondary Outcome

Title	Duration of Severe Neutropenia (DSN) in Cycles 2, 3 and 4
Description	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)

Outcome Measure Data

Analysis Population Description

ITT population included all participants who were randomized.

Arm/Group Title	(Arm 1): SPI-2012 and TC	(Arm 2): Pegfilgrastim and TC
Arm/Group Description	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.	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.
Measure Participants	118	119
Cycle 2	0.08 (0.267)	0.09 (0.432)
Cycle 3	0.07 (0.252)	0.07 (0.283)
Cycle 4	0.07 (0.252)	0.08 (0.266)

6. Secondary Outcome

Title	Number of Participants With Neutropenic Complications in Cycle 1
Description	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)

Outcome Measure Data

Analysis Population Description

ITT population included all participants who were randomized.

Arm/Group Title	(Arm 1): SPI-2012 and TC	(Arm 2): Pegfilgrastim and TC
Arm/Group Description	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.	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.
Measure Participants	118	119
Count of Participants [Participants]	1 0.8%	5 4.2%

7. Secondary Outcome

Title	Number of Participants With Febrile Neutropenia in Cycles 2, 3 and 4
Description	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)

Outcome Measure Data

Analysis Population Description

ITT population included all participants who were randomized.

Arm/Group Title	(Arm 1): SPI-2012 and TC	(Arm 2): Pegfilgrastim and TC
Arm/Group Description	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.	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.
Measure Participants	118	119
Cycle 2	0 0%	2 1.7%
Cycle 3	0 0%	0 0%
Cycle 4	0 0%	0 0%

8. Secondary Outcome

Title	Relative Dose Intensity (RDI) of TC Chemotherapy
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	(Arm 1): SPI-2012 and TC	(Arm 2): Pegfilgrastim and TC
Arm/Group Description	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.	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.
Measure Participants	117	118
Docetaxel	96.9 (7.70)	98.4 (7.89)
Cyclophosphamide	98.4 (5.27)	98.8 (6.40)

9. Secondary Outcome

Title	Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs), and Death
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	(Arm 1): SPI-2012 and TC	(Arm 2): Pegfilgrastim and TC	(Arm 1): SPI-2012 and TC: Follow-up Period	Arm 2: Pegfilgrastim and TC: Follow-up Period
Arm/Group Description	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.	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.	In addition to the treatment period, long-term safety follow-up continued for 12 months after last study treatment.	In addition to the treatment period, long-term safety follow-up continued for 12 months after last study treatment
Measure Participants	117	118	117	118
TEAEs	115 97.5%	116 97.5%	33 13.9%	48 NaN
SAEs	12 10.2%	19 16%	2 0.8%	4 NaN
Death	0 0%	1 0.8%	0 0%	0 NaN

10. Secondary Outcome

Title	Number of Participants With Clinically Significant Laboratory Abnormalities
Description	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)

Outcome Measure Data

Analysis Population Description

SAF population included all participants who received at least one dose of any protocol-specified drug (TC or SPI-2012 or pegfilgrastim).

Arm/Group Title	(Arm 1): SPI-2012 and TC	(Arm 2): Pegfilgrastim and TC
Arm/Group Description	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.	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.
Measure Participants	117	118
Hematology: Basophils	0 0%	0 0%
Hematology: Basophils/Leukocytes	0 0%	0 0%
Hematology: Eosinophils	0 0%	0 0%
Hematology: Eosinophils/Leukocytes	0 0%	0 0%
Hematology: Hematocrit	4 3.4%	2 1.7%
Hematology: Hemoglobin	6 5.1%	4 3.4%
Hematology: Lymphocytes	0 0%	0 0%
Hematology: Lymphocytes/Leukocytes	6 5.1%	13 10.9%
Hematology: Monocytes	0 0%	0 0%
Hematology: Monocytes/Leukocytes	0 0%	0 0%
Hematology: Neutrophils	17 14.4%	23 19.3%
Hematology: Neutrophils/Leukocytes	12 10.2%	9 7.6%
Hematology: Platelets	10 8.5%	2 1.7%
Hematology: White Blood Cells	16 13.6%	18 15.1%
Chemistry: Alanine aminotransferase	2 1.7%	1 0.8%
Chemistry: Alkaline phosphatase	0 0%	1 0.8%
Chemistry: Aspartate aminotransferase	1 0.8%	1 0.8%
Chemistry: Bilirubin	0 0%	0 0%
Chemistry: Calcium	1 0.8%	1 0.8%
Chemistry: Cholesterol	0 0%	0 0%
Chemistry: Creatinine	0 0%	0 0%
Chemistry: Potassium	0 0%	1 0.8%
Chemistry: Sodium	0 0%	2 1.7%
Chemistry: Triglycerides	0 0%	0 0%

Adverse 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)
Adverse Event Reporting Description	The Safety Analysis Population included all participants who received at least one dose of any protocol-specified drug (TC or SPI-2012 or pegfilgrastim). Adverse events data was summarized and reported for Treatment and Follow-up period separately for both groups.
Arm/Group Title	(Arm 1): SPI-2012 and TC		(Arm 2): Pegfilgrastim and TC		(Arm 1): SPI-2012 and TC: Follow-up Period		(Arm 2): Pegfilgrastim and TC: Follow-up Period
Arm/Group Description	At each cycle for 4 cycles, participants received SPI-2012 at a fixed dose of 13.2 mg / 0.6 mL, [3.6 mg 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 the last study treatment or patient discontinuation.		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 the last study treatment or patient discontinuation.		In addition to the treatment period, long-term safety follow-up continued for 12 months after last study treatment.		In addition to the treatment period, long-term safety follow-up continued for 12 months after last study treatment.
All Cause Mortality
	(Arm 1): SPI-2012 and TC		(Arm 2): Pegfilgrastim and TC		(Arm 1): SPI-2012 and TC: Follow-up Period		(Arm 2): Pegfilgrastim and TC: Follow-up Period
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/117 (0%)		1/118 (0.8%)		0/117 (0%)		0/118 (0%)
Serious Adverse Events
	(Arm 1): SPI-2012 and TC		(Arm 2): Pegfilgrastim and TC		(Arm 1): SPI-2012 and TC: Follow-up Period		(Arm 2): Pegfilgrastim and TC: Follow-up Period
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/117 (10.3%)		19/118 (16.1%)		2/117 (1.7%)		4/118 (3.4%)
Blood and lymphatic system disorders
Febrile neutropenia	0/117 (0%)		2/118 (1.7%)		0/117 (0%)		0/118 (0%)
Neutropenia	0/117 (0%)		3/118 (2.5%)		0/117 (0%)		0/118 (0%)
Cardiac disorders
Sinus tachycardia	0/117 (0%)		1/118 (0.8%)		0/117 (0%)		0/118 (0%)
Supraventricular tachycardia	1/117 (0.9%)		0/118 (0%)		0/117 (0%)		0/118 (0%)
Cardiac arrest	0/117 (0%)		0/118 (0%)		1/117 (0.9%)		0/118 (0%)
Myocardial infarction	0/117 (0%)		0/118 (0%)		1/117 (0.9%)		0/118 (0%)
Gastrointestinal disorders
Diarrhoea	1/117 (0.9%)		0/118 (0%)		0/117 (0%)		0/118 (0%)
Enterocolitis	0/117 (0%)		1/118 (0.8%)		0/117 (0%)		0/118 (0%)
Nausea	1/117 (0.9%)		0/118 (0%)		0/117 (0%)		0/118 (0%)
Vomiting	1/117 (0.9%)		0/118 (0%)		0/117 (0%)		0/118 (0%)
General disorders
Administration site reaction	0/117 (0%)		1/118 (0.8%)		0/117 (0%)		0/118 (0%)
Chest pain	1/117 (0.9%)		1/118 (0.8%)		0/117 (0%)		0/118 (0%)
Pyrexia	1/117 (0.9%)		1/118 (0.8%)		0/117 (0%)		0/118 (0%)
Infections and infestations
Bronchitis	1/117 (0.9%)		1/118 (0.8%)		0/117 (0%)		0/118 (0%)
Bronchitis viral	0/117 (0%)		1/118 (0.8%)		0/117 (0%)		0/118 (0%)
Cellulitis	0/117 (0%)		1/118 (0.8%)		0/117 (0%)		0/118 (0%)
Chest wall abscess	0/117 (0%)		1/118 (0.8%)		0/117 (0%)		0/118 (0%)
Cystitis	0/117 (0%)		1/118 (0.8%)		0/117 (0%)		0/118 (0%)
Enterocolitis infectious	1/117 (0.9%)		0/118 (0%)		0/117 (0%)		0/118 (0%)
Escherichia bacteraemia	1/117 (0.9%)		0/118 (0%)		0/117 (0%)		0/118 (0%)
Herpes zoster	1/117 (0.9%)		0/118 (0%)		0/117 (0%)		0/118 (0%)
Pneumonia	0/117 (0%)		2/118 (1.7%)		0/117 (0%)		0/118 (0%)
Pyelonephritis	1/117 (0.9%)		0/118 (0%)		0/117 (0%)		0/118 (0%)
Sepsis	1/117 (0.9%)		1/118 (0.8%)		0/117 (0%)		0/118 (0%)
Urinary tract infection	0/117 (0%)		1/118 (0.8%)		0/117 (0%)		0/118 (0%)
Injury, poisoning and procedural complications
Fall	2/117 (1.7%)		0/118 (0%)		0/117 (0%)		0/118 (0%)
Ligament sprain	0/117 (0%)		1/118 (0.8%)		0/117 (0%)		0/118 (0%)
Rib fracture	0/117 (0%)		1/118 (0.8%)		0/117 (0%)		0/118 (0%)
Seroma	0/117 (0%)		0/118 (0%)		0/117 (0%)		1/118 (0.8%)
Investigations
Neutrophil count decreased	0/117 (0%)		1/118 (0.8%)		0/117 (0%)		0/118 (0%)
White blood cell count decreased	0/117 (0%)		1/118 (0.8%)		0/117 (0%)		0/118 (0%)
Metabolism and nutrition disorders
Dehydration	0/117 (0%)		1/118 (0.8%)		0/117 (0%)		0/118 (0%)
Fluid overload	0/117 (0%)		1/118 (0.8%)		0/117 (0%)		0/118 (0%)
Musculoskeletal and connective tissue disorders
Back pain	0/117 (0%)		1/118 (0.8%)		0/117 (0%)		0/118 (0%)
Muscular weakness	0/117 (0%)		0/118 (0%)		0/117 (0%)		1/118 (0.8%)
Nervous system disorders
Syncope	0/117 (0%)		1/118 (0.8%)		0/117 (0%)		0/118 (0%)
Cerebrovascular accident	0/117 (0%)		0/118 (0%)		0/117 (0%)		1/118 (0.8%)
Dizziness	0/117 (0%)		0/118 (0%)		0/117 (0%)		1/118 (0.8%)
Psychiatric disorders
Delirium	0/117 (0%)		1/118 (0.8%)		0/117 (0%)		0/118 (0%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	0/117 (0%)		1/118 (0.8%)		0/117 (0%)		0/118 (0%)
Dyspnoea	0/117 (0%)		2/118 (1.7%)		0/117 (0%)		0/118 (0%)
Skin and subcutaneous tissue disorders
Skin disorder	1/117 (0.9%)		0/118 (0%)		0/117 (0%)		0/118 (0%)
Vascular disorders
Deep vein thrombosis	0/117 (0%)		1/118 (0.8%)		0/117 (0%)		0/118 (0%)
Hypotension	0/117 (0%)		1/118 (0.8%)		0/117 (0%)		0/118 (0%)
Other (Not Including Serious) Adverse Events
	(Arm 1): SPI-2012 and TC		(Arm 2): Pegfilgrastim and TC		(Arm 1): SPI-2012 and TC: Follow-up Period		(Arm 2): Pegfilgrastim and TC: Follow-up Period
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	115/117 (98.3%)		116/118 (98.3%)		33/117 (28.2%)		48/118 (40.7%)
Blood and lymphatic system disorders
Neutropenia	37/117 (31.6%)		37/118 (31.4%)		0/117 (0%)		0/118 (0%)
Anaemia	22/117 (18.8%)		11/118 (9.3%)		1/117 (0.9%)		2/118 (1.7%)
Lymphopenia	10/117 (8.5%)		9/118 (7.6%)		1/117 (0.9%)		0/118 (0%)
Cardiac disorders
Tachycardia	5/117 (4.3%)		6/118 (5.1%)		0/117 (0%)		0/118 (0%)
Eye disorders
Lacrimation increased	2/117 (1.7%)		7/118 (5.9%)		0/117 (0%)		1/118 (0.8%)
Gastrointestinal disorders
Nausea	50/117 (42.7%)		61/118 (51.7%)		1/117 (0.9%)		1/118 (0.8%)
Diarrhoea	38/117 (32.5%)		40/118 (33.9%)		1/117 (0.9%)		3/118 (2.5%)
Constipation	26/117 (22.2%)		24/118 (20.3%)		0/117 (0%)		2/118 (1.7%)
Abdominal pain	14/117 (12%)		20/118 (16.9%)		0/117 (0%)		2/118 (1.7%)
Vomiting	14/117 (12%)		19/118 (16.1%)		1/117 (0.9%)		0/118 (0%)
Dyspepsia	14/117 (12%)		9/118 (7.6%)		1/117 (0.9%)		0/118 (0%)
Stomatitis	9/117 (7.7%)		10/118 (8.5%)		0/117 (0%)		0/118 (0%)
Dry mouth	3/117 (2.6%)		9/118 (7.6%)		0/117 (0%)		0/118 (0%)
General disorders
Fatigue	40/117 (34.2%)		51/118 (43.2%)		0/117 (0%)		0/118 (0%)
Pyrexia	25/117 (21.4%)		26/118 (22%)		1/117 (0.9%)		0/118 (0%)
Oedema peripheral	12/117 (10.3%)		15/118 (12.7%)		2/117 (1.7%)		2/118 (1.7%)
Asthenia	15/117 (12.8%)		11/118 (9.3%)		0/117 (0%)		0/118 (0%)
Pain	5/117 (4.3%)		11/118 (9.3%)		0/117 (0%)		1/118 (0.8%)
Chills	4/117 (3.4%)		6/118 (5.1%)		0/117 (0%)		1/118 (0.8%)
Malaise	3/117 (2.6%)		6/118 (5.1%)		0/117 (0%)		0/118 (0%)
Infections and infestations
Upper respiratory tract infection	5/117 (4.3%)		9/118 (7.6%)		1/117 (0.9%)		2/118 (1.7%)
Nasopharyngitis	3/117 (2.6%)		6/118 (5.1%)		1/117 (0.9%)		0/118 (0%)
Urinary tract infection	3/117 (2.6%)		7/118 (5.9%)		0/117 (0%)		3/118 (2.5%)
Candida infection	1/117 (0.9%)		7/118 (5.9%)		0/117 (0%)		0/118 (0%)
Injury, poisoning and procedural complications
Radiation skin injury	0/117 (0%)		0/118 (0%)		2/117 (1.7%)		6/118 (5.1%)
Investigations
Lymphocyte count decreased	44/117 (37.6%)		54/118 (45.8%)		0/117 (0%)		1/118 (0.8%)
White blood cell count decreased	22/117 (18.8%)		31/118 (26.3%)		1/117 (0.9%)		2/118 (1.7%)
Neutrophil count decreased	16/117 (13.7%)		22/118 (18.6%)		1/117 (0.9%)		0/118 (0%)
Platelet count decreased	12/117 (10.3%)		3/118 (2.5%)		0/117 (0%)		0/118 (0%)
White blood cell count increased	9/117 (7.7%)		3/118 (2.5%)		0/117 (0%)		0/118 (0%)
Metabolism and nutrition disorders
Decreased appetite	23/117 (19.7%)		19/118 (16.1%)		0/117 (0%)		0/118 (0%)
Hypokalaemia	4/117 (3.4%)		8/118 (6.8%)		2/117 (1.7%)		2/118 (1.7%)
Dehydration	3/117 (2.6%)		8/118 (6.8%)		0/117 (0%)		0/118 (0%)
Musculoskeletal and connective tissue disorders
Bone pain	47/117 (40.2%)		51/118 (43.2%)		1/117 (0.9%)		1/118 (0.8%)
Myalgia	26/117 (22.2%)		23/118 (19.5%)		0/117 (0%)		3/118 (2.5%)
Back pain	18/117 (15.4%)		15/118 (12.7%)		2/117 (1.7%)		3/118 (2.5%)
Arthralgia	17/117 (14.5%)		12/118 (10.2%)		4/117 (3.4%)		7/118 (5.9%)
Pain in extremity	14/117 (12%)		11/118 (9.3%)		1/117 (0.9%)		0/118 (0%)
Nervous system disorders
Headache	31/117 (26.5%)		35/118 (29.7%)		0/117 (0%)		1/118 (0.8%)
Dysgeusia	9/117 (7.7%)		16/118 (13.6%)		0/117 (0%)		0/118 (0%)
Neuropathy peripheral	9/117 (7.7%)		14/118 (11.9%)		1/117 (0.9%)		1/118 (0.8%)
Dizziness	6/117 (5.1%)		12/118 (10.2%)		1/117 (0.9%)		1/118 (0.8%)
Psychiatric disorders
Insomnia	18/117 (15.4%)		11/118 (9.3%)		1/117 (0.9%)		1/118 (0.8%)
Anxiety	5/117 (4.3%)		8/118 (6.8%)		0/117 (0%)		0/118 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	8/117 (6.8%)		17/118 (14.4%)		2/117 (1.7%)		0/118 (0%)
Cough	8/117 (6.8%)		14/118 (11.9%)		1/117 (0.9%)		1/118 (0.8%)
Oropharyngeal pain	9/117 (7.7%)		10/118 (8.5%)		0/117 (0%)		0/118 (0%)
Epistaxis	4/117 (3.4%)		7/118 (5.9%)		0/117 (0%)		0/118 (0%)
Skin and subcutaneous tissue disorders
Alopecia	40/117 (34.2%)		43/118 (36.4%)		1/117 (0.9%)		0/118 (0%)
Rash	13/117 (11.1%)		11/118 (9.3%)		0/117 (0%)		1/118 (0.8%)
Pruritus	10/117 (8.5%)		9/118 (7.6%)		0/117 (0%)		2/118 (1.7%)
Erythema	4/117 (3.4%)		6/118 (5.1%)		0/117 (0%)		0/118 (0%)
Vascular disorders
Flushing	9/117 (7.7%)		10/118 (8.5%)		0/117 (0%)		2/118 (1.7%)
Hot flush	10/117 (8.5%)		8/118 (6.8%)		1/117 (0.9%)		3/118 (2.5%)
Hypertension	4/117 (3.4%)		8/118 (6.8%)		1/117 (0.9%)		3/118 (2.5%)
Hypotension	6/117 (5.1%)		3/118 (2.5%)		0/117 (0%)		0/118 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.