PROTECT-1: Phase III Study Comparing the Efficacy and Safety of LA-EP2006 and Neulasta®

• Sponsor: Sandoz (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01735175
• Collaborator: Sandoz GmbH (Industry)
• Enrollment: 316
• Locations: 41
• Arms: 2
• Duration (Months): 20
• Patients Per Site: 7.7
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The study will assess the efficacy of LA-EP2006 compared to Neulasta® with respect to the mean duration of severe neutropenia during treatment with myelosuppressive chemotherapy in breast cancer patients.

Condition or Disease	Intervention/Treatment	Phase
Neutropenic Complications; Breast Neoplasms; Chemotherapy-induced Neutropenia; Chemotherapeutic Toxicity	Drug: LA-EP2006; Drug: Neulasta®	Phase 3

Detailed Description

This randomized, double-blind trial compared the proposed biosimilar LA-EP2006 with the reference Neulasta® in women (≥18 years) receiving chemotherapy for breast cancer. Therefore patients were randomized to receive LA-EP2006 (n = 159) or the reference product (n = 157) for ≤6 cycles of (neo)-adjuvant TAC (docetaxel 75mg/m^{2, doxorubicin 50 mg/m}2, and cyclophosphamide 500mg/m^{2) chemotherapy. The primary end point was the duration of severe neutropenia (DSN) during Cycle 1 (defined as number of consecutive days with absolute neutrophil count <0.5 × 10}9/l). The equivalence was confirmed if 95% CIs were within a ±1 day margin. LA-EP2006 was equivalent to the reference product in DSN (difference: 0.07 days; 95% CI [-0.12, 0.26]). Further, LA-EP2006 and the reference Neulasta® showed no clinically meaningful differences regarding efficacy and safety.

Study Design

• Study Type: Interventional
• Actual Enrollment: 316 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Supportive Care
• Official Title: A Randomized, Double-blind, Parallel-group, Multi-center Phase 3 Comparative Study Investigating Efficacy and Safety of LA-EP2006 and Neulasta® in Breast Cancer Patients Treated With Myelosuppressive Chemotherapy
• Study Start Date: Jun 1, 2012
• Actual Primary Completion Date: May 1, 2013
• Actual Study Completion Date: Feb 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Neulasta® During each chemotherapy cycle eligible patients receive Neulasta® s.c. post chemotherapy application.	Drug: Neulasta®; Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.; Other Names: pegfilgrastim
Experimental: LA-EP2006 During each chemotherapy cycle eligible patients receive LA-EP2006 s.c. post chemotherapy application.	Drug: LA-EP2006; Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.; Other Names: pegfilgrastim

Outcome Measures

Primary Outcome Measures

1. Mean Duration of Severe Neutropenia (DSN) During Cycle 1 of Chemotherapy [21 days (Cycle 1 of chemotherapy treatment)]

   Mean duration of severe neutropenia, defined as number of consecutive days with ANC <0.5 × 10^9 cells/L (grade 4 neutropenia).

Secondary Outcome Measures

1. Incidence of Febrile Neutropenia (FN) [across all cycles (18 weeks)]

   FN was defined as an oral temperature ≥ 38.3°C while having an absolute neutrophil count (ANC) < 0.5 × 10^9 cells/L. Serious treatment-emergent adverse events (TEAEs) were reconciled with the fever and ANC results recorded in the patient diary and CRF and therefore only the serious TEAEs of FN ("febrile neutropenia", "neutropenic sepsis") were taken into account.

2. Number of Patients With at Least One Episode of Fever by Cycle and Across All Cycles [across al cycles (18 weeks)]

   Fever was defined as an oral temperature ≥ 38.3°C. Fever episodes were characterized by maximum oral temperature and the number of patients who had fever at least once.

3. Depth of ANC Nadir in Cycle 1 [Cycle 1 (3 weeks)]

   The depth of ANC nadir was defined as the patient's lowest ANC (10^9 cells/L) in Cycle 1. Only the evaluable patients with a depth of ANC in Cycle 1 are given.

4. Number of Patients With ANC Nadir Per Day in Cycle 1 [Cycle 1 (3 weeks)]

   Numbers of patients with ANC nadir based per day during Cycle 1 are given.

5. Time to ANC Recovery in Days in Cycle 1 [across Cycle 1 (3 weeks)]

   Time to absolute neutrophil count (ANC) recovery in Cycle 1 was defined as the time in days from ANC nadir until the patient's ANC had increased to ≥ 2 × 10^9 cells/L. Only the evaluable patients with a depth of ANC in Cycle 1 and a later increase of ANC ≥ 2 × 10^9 cells/L are given.

6. Frequency of Infections by Cycle and Across All Cycles [across all cycles (18 weeks)]

   The number of patients with infections was recorded for each cycle and across all cycles. Infections were identified by the AE documentation page selecting all events coded with System Organ Class "Infections and Infestations".

7. Mortality Due to Infection [Study course (41 weeks)]

   Number of patients with death due to infections

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• histologically proven breast cancer

• eligible for six cycles of neoadjuvant or adjuvant chemotherapy

Exclusion Criteria:

• concurrent or prior chemotherapy for breast cancer

• concurrent or prior anti-cancer treatment for breast cancer such as endocrine therapy, immunotherapy, monoclonal antibodies, and/or biological therapy

• concurrent prophylactic antibiotics

• previous therapy with any G-CSF (granulocyte-colony stimulating factor) product

Other protocol-defined inclusion/exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sandoz Investigational Site	Ijui		Brazil	98700-000
2	Sandoz Investigational Site	Lajeado		Brazil	95900-000
3	Sandoz Investigational Site	Santo Andre		Brazil	0960-650
4	Sandoz Investigational Site	Andhra Pradesh		India	530002
5	Sandoz Investigational Site	Delhi		India	110095
6	Sandoz Investigational Site	Madurai		India	625107
7	Sandoz Investigational Site	Maharashtra		India	411001
8	Sandoz Investigational Site	Maharashtra		India	416008
9	Sandoz Investigational Site	Maharashtra		India	440010
10	Sandoz Investigational Site	Mumbai		India	422005
11	Sandoz Investigational Site	Rajasthan		India	302013
12	Sandoz Investigational Site	Aguascalientes		Mexico	20230
13	Sandoz Investigational Site	Juchitan		Mexico	70000
14	Sandoz Investigational Site	Bucharest		Romania	11461
15	Sandoz Investigational Site	Bucharest		Romania	23423
16	Sandoz Investigational Site	Iasi		Romania	700106
17	Sandoz Investigational Site	Suceava		Romania	720237
18	Sandoz Investigational Site	Barnaul		Russian Federation	656052
19	Sandoz Investigational Site	Bashkortostan		Russian Federation	450054
20	Sandoz Investigational Site	Berdsk		Russian Federation	633004
21	Sandoz Investigational Site	Ivanovo		Russian Federation	153040
22	Sandoz Investigational Site	Kabardino		Russian Federation	361045
23	Sandoz Investigational Site	Kazan		Russian Federation	420029
24	Sandoz Investigational Site	Krasnodar		Russian Federation	354057
25	Sandoz Investigational Site	Kursk		Russian Federation	305035
26	Sandoz Investigational Site	Leningrad		Russian Federation	188663
27	Sandoz Investigational Site	Moscow		Russian Federation	115478
28	Sandoz Investigational Site	Novgorod		Russian Federation	173016
29	Sandoz Investigational Site	Oktyabrskaya		Russian Federation	355047
30	Sandoz Investigational Site	Ryazan		Russian Federation	390011
31	Sandoz Investigational Site	St. Petersburg		Russian Federation	195067
32	Sandoz Investigational Site	Tula		Russian Federation	300053
33	Sandoz Investigational Site	Cherkasy		Ukraine	18009
34	Sandoz Investigational Site	Chernivtsi		Ukraine	58013
35	Sandoz Investigational Site	Dnipropetrovsk		Ukraine	49102
36	Sandoz Investigational Site	Kharkiv		Ukraine	61176
37	Sandoz Investigational Site	Kriviy Rig		Ukraine	50048
38	Sandoz Investigational Site	Lugansk		Ukraine	91000
39	Sandoz Investigational Site	Mariupol		Ukraine	87500
40	Sandoz Investigational Site	Vinnytsya		Ukraine	21029
41	Sandoz Investigational Site	Zaporizhzhia		Ukraine	69040

Sponsors and Collaborators

• Sandoz
• Sandoz GmbH

Investigators

• Study Chair: Sandoz Biopharmaceutical Clinical Development, Sandoz

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sandoz
• ClinicalTrials.gov Identifier: NCT01735175
• Other Study ID Numbers: LA-EP06-301; 2011-004532-58
• First Posted: Nov 28, 2012
• Last Update Posted: Aug 7, 2017
• Last Verified: Jun 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Keywords provided by Sandoz: biosimilars; Pegfilgrastim,; G-CSF,; neutropenia,; breast cancer,; myelosuppressive chemotherapy,; supportive care; granulocyte-colony-stimulating factor
• Additional relevant MeSH terms: Breast Neoplasms; Neutropenia

Study Results

Participant Flow

Arm/Group Title	LA-EP2006	Neulasta®
Arm/Group Description	During each chemotherapy cycle eligible patients receive LA-EP2006 s.c. post chemotherapy application. LA-EP2006: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.	During each chemotherapy cycle eligible patients receive Neulasta® s.c. post chemotherapy application. Neulasta®: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.
Period Title: Overall Study
STARTED	159	157
Completed All Cycles	141	150
Completed All Treatments as Planned	140	150
Completed the 6-month SFU Visit	120	138
COMPLETED	130	144
NOT COMPLETED	29	13

Baseline Characteristics

Arm/Group Title	LA-EP2006	Neulasta®	Total
Arm/Group Description	During each chemotherapy cycle eligible patients receive LA-EP2006 s.c. post chemotherapy application. LA-EP2006: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.	During each chemotherapy cycle eligible patients receive Neulasta® s.c. post chemotherapy application. Neulasta®: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.	Total of all reporting groups
Overall Participants	159	157	316
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	49.9 (9.53)	50.5 (10.87)	50.2 (10.20)
Sex: Female, Male (Count of Participants)
Female	159 100%	157 100%	316 100%
Male	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	11 6.9%	18 11.5%	29 9.2%
Not Hispanic or Latino	148 93.1%	139 88.5%	287 90.8%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	28 17.6%	26 16.6%	54 17.1%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	129 81.1%	127 80.9%	256 81%
More than one race	2 1.3%	4 2.5%	6 1.9%
Unknown or Not Reported	0 0%	0 0%	0 0%
BMI (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	27.47 (26.76)	27.44 (26.35)	27.45 (26.40)
Time since diagnosis (months) [Median (Full Range) ]
Median (Full Range) [months]	1.35	1.38	1.38
Disease stage (Count of Participants)
I	4 2.5%	3 1.9%	7 2.2%
II	74 46.5%	73 46.5%	147 46.5%
III	81 50.9%	78 49.7%	159 50.3%
IV	0 0%	3 1.9%	3 0.9%
Previous breast cancer surgery (Count of Participants)
Count of Participants [Participants]	149 93.7%	146 93%	295 93.4%
Previous radiotherapy (Count of Participants)
Count of Participants [Participants]	7 4.4%	9 5.7%	16 5.1%
ECOG performance status (Count of Participants)
0 (fully active)	128 80.5%	123 78.3%	251 79.4%
1 (restricted in physically strenuous activity)	31 19.5%	34 21.7%	65 20.6%

Outcome Measures

1. Primary Outcome

Title	Mean Duration of Severe Neutropenia (DSN) During Cycle 1 of Chemotherapy
Description	Mean duration of severe neutropenia, defined as number of consecutive days with ANC <0.5 × 10^9 cells/L (grade 4 neutropenia).
Time Frame	21 days (Cycle 1 of chemotherapy treatment)

Outcome Measure Data

Analysis Population Description

FAS set = full analysis set; PP set = per protocol set

Arm/Group Title	LA-EP2006	Neulasta®
Arm/Group Description	During each chemotherapy cycle eligible patients receive LA-EP2006 s.c. post chemotherapy application. LA-EP2006: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.	During each chemotherapy cycle eligible patients receive Neulasta® s.c. post chemotherapy application. Neulasta®: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.
Measure Participants	159	157
FAS	0.75 (0.878)	0.83 (0.898)
PP	0.75 (0.875)	0.79 (0.872)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LA-EP2006, Neulasta®
	Comments	The hierarchical test procedure aimed to show that LA-EP2006 and Neulasta® are equivalent with respect to DSN duration in Cycle 1 (margin±1 day), and, if so LA-EP2006 is non-inferior to Neulasta® with respect to DSN duration in Cycle 1 (margin of -0.6 days).
	Type of Statistical Test	Equivalence
	Comments	The testing procedure was set up in a hierarchical structure, where first equivalence between LA-EP2006 and Neulasta® was assessed (margin ±1 day) and only if this was successfully established, non-inferiority between the two products was tested using a tighter margin of -0.6 days.
Statistical Test of Hypothesis	p-Value	0.05
	Comments
	Method	ANCOVA
	Comments	The primary endpoints was analyzed with analysis of covariance (ANCOVA).
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.07
	Confidence Interval	(2-Sided) 95%; -0.12 to 0.26
	Parameter Dispersion	Type: Value:
	Estimation Comments	The difference between LA-EP2006 and reference pegfilgrastim was 0.07 days (95% CI [-0.12, 0.26]). 95% CIs were within the predefined margin of ±1 day confirming equivalence.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	LA-EP2006, Neulasta®
	Comments	The hierarchical test procedure aimed to show that LA-EP2006 and Neulasta® are equivalent with respect to DSN duration in Cycle 1 (margin±1 day), and, if so LA-EP2006 is non-inferior to Neulasta® with respect to DSN duration in Cycle 1 (margin of -0.6 days).
	Type of Statistical Test	Non-Inferiority
	Comments	The testing procedure was set up in a hierarchical structure, where first equivalence between LA-EP2006 and Neulasta was assessed (margin ±1 day) and only if this was successfully established, non-inferiority between the two products was tested using a tighter margin of -0.6 days.
Statistical Test of Hypothesis	p-Value	0.05
	Comments
	Method	ANCOVA
	Comments	The primary endpoints was analyzed with analysis of covariance (ANCOVA).
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.07
	Confidence Interval	(2-Sided) 95%; -0.12 to 0.26
	Parameter Dispersion	Type: Value:
	Estimation Comments	LA-EP2006 is non-inferior to Neulasta® because the lower bound of the 95% CI is entirely above the non-inferiority margin of -0.6 days.

2. Secondary Outcome

Title	Incidence of Febrile Neutropenia (FN)
Description	FN was defined as an oral temperature ≥ 38.3°C while having an absolute neutrophil count (ANC) < 0.5 × 10^9 cells/L. Serious treatment-emergent adverse events (TEAEs) were reconciled with the fever and ANC results recorded in the patient diary and CRF and therefore only the serious TEAEs of FN ("febrile neutropenia", "neutropenic sepsis") were taken into account.
Time Frame	across all cycles (18 weeks)

Outcome Measure Data

Analysis Population Description

Number of patients with at least one episode of febrile neutropenia by cycle and across all cycles (FAS set)

Arm/Group Title	LA-EP2006	Neulasta®
Arm/Group Description	During each chemotherapy cycle eligible patients receive LA-EP2006 s.c. post chemotherapy application. LA-EP2006: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.	During each chemotherapy cycle eligible patients receive Neulasta® s.c. post chemotherapy application. Neulasta®: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.
Measure Participants	159	157
Cycle 1	6 3.8%	11 7%
Cycle 2	2 1.3%	1 0.6%
Cycle 3	2 1.3%	1 0.6%
Cycle 4	1 0.6%	0 0%
Cycle 5	2 1.3%	0 0%
Cycle 6	1 0.6%	1 0.6%
All cycles (at least on incidence)	9 5.7%	12 7.6%

3. Secondary Outcome

Title	Number of Patients With at Least One Episode of Fever by Cycle and Across All Cycles
Description	Fever was defined as an oral temperature ≥ 38.3°C. Fever episodes were characterized by maximum oral temperature and the number of patients who had fever at least once.
Time Frame	across al cycles (18 weeks)

Outcome Measure Data

Analysis Population Description

Patients with more than 1 event during the study (overall) are counted only once. FAS set = full analysis set

Arm/Group Title	LA-EP2006	Neulasta®
Arm/Group Description	During each chemotherapy cycle eligible patients receive LA-EP2006 s.c. post chemotherapy application. LA-EP2006: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.	During each chemotherapy cycle eligible patients receive Neulasta® s.c. post chemotherapy application. Neulasta®: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.
Measure Participants	159	157
Cycle 1	9 5.7%	14 8.9%
Cycle 2	6 3.8%	2 1.3%
Cycle 3	7 4.4%	6 3.8%
Cycle 4	5 3.1%	2 1.3%
Cycle 5	7 4.4%	4 2.5%
Cycle 6	5 3.1%	3 1.9%
Overall	26 16.4%	26 16.6%

4. Secondary Outcome

Title	Depth of ANC Nadir in Cycle 1
Description	The depth of ANC nadir was defined as the patient's lowest ANC (10^9 cells/L) in Cycle 1. Only the evaluable patients with a depth of ANC in Cycle 1 are given.
Time Frame	Cycle 1 (3 weeks)

Outcome Measure Data

Analysis Population Description

FAS set = full analysis set

Arm/Group Title	LA-EP2006	Neulasta®
Arm/Group Description	During each chemotherapy cycle eligible patients receive LA-EP2006 s.c. post chemotherapy application. LA-EP2006: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.	During each chemotherapy cycle eligible patients receive Neulasta® s.c. post chemotherapy application. Neulasta®: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.
Measure Participants	156	155
Mean (Standard Deviation) [10^9 cells/L]	1.102 (1.5398)	0.921 (1.1771)

5. Secondary Outcome

Title	Number of Patients With ANC Nadir Per Day in Cycle 1
Description	Numbers of patients with ANC nadir based per day during Cycle 1 are given.
Time Frame	Cycle 1 (3 weeks)

Outcome Measure Data

Analysis Population Description

FAS set = full analysis set

Arm/Group Title	LA-EP2006	Neulasta®
Arm/Group Description	During each chemotherapy cycle eligible patients receive LA-EP2006 s.c. post chemotherapy application. LA-EP2006: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.	During each chemotherapy cycle eligible patients receive Neulasta® s.c. post chemotherapy application. Neulasta®: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.
Measure Participants	159	157
Days 1-5	5 3.1%	5 3.2%
Day 6	7 4.4%	4 2.5%
Day 7	101 63.5%	104 66.2%
Day 8	34 21.4%	25 15.9%
Day 9	1 0.6%	7 4.5%
Days 10-15	8 5%	10 6.4%

6. Secondary Outcome

Title	Time to ANC Recovery in Days in Cycle 1
Description	Time to absolute neutrophil count (ANC) recovery in Cycle 1 was defined as the time in days from ANC nadir until the patient's ANC had increased to ≥ 2 × 10^9 cells/L. Only the evaluable patients with a depth of ANC in Cycle 1 and a later increase of ANC ≥ 2 × 10^9 cells/L are given.
Time Frame	across Cycle 1 (3 weeks)

Outcome Measure Data

Analysis Population Description

FAS set = full analysis set

Arm/Group Title	LA-EP2006	Neulasta®
Arm/Group Description	During each chemotherapy cycle eligible patients receive LA-EP2006 s.c. post chemotherapy application. LA-EP2006: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.	During each chemotherapy cycle eligible patients receive Neulasta® s.c. post chemotherapy application. Neulasta®: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.
Measure Participants	154	154
Mean (Standard Deviation) [days]	1.58 (1.053)	1.72 (1.100)

7. Secondary Outcome

Title	Frequency of Infections by Cycle and Across All Cycles
Description	The number of patients with infections was recorded for each cycle and across all cycles. Infections were identified by the AE documentation page selecting all events coded with System Organ Class "Infections and Infestations".
Time Frame	across all cycles (18 weeks)

Outcome Measure Data

Analysis Population Description

Patients with more than 1 event during the study (overall) are counted only once. FAS set = full analysis set

Arm/Group Title	LA-EP2006	Neulasta®
Arm/Group Description	During each chemotherapy cycle eligible patients receive LA-EP2006 s.c. post chemotherapy application. LA-EP2006: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.	During each chemotherapy cycle eligible patients receive Neulasta® s.c. post chemotherapy application. Neulasta®: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.
Measure Participants	159	157
Cycle 1	7 4.4%	4 2.5%
Cycle 2	6 3.8%	5 3.2%
Cycle 3	3 1.9%	8 5.1%
Cycle 4	2 1.3%	3 1.9%
Cycle 5	11 6.9%	4 2.5%
Cycle 6	5 3.1%	3 1.9%
Overall	22 13.8%	24 15.3%

8. Secondary Outcome

Title	Mortality Due to Infection
Description	Number of patients with death due to infections
Time Frame	Study course (41 weeks)

Outcome Measure Data

Analysis Population Description

FAS set = full analysis set

Arm/Group Title	LA-EP2006	Neulasta®
Arm/Group Description	During each chemotherapy cycle eligible patients receive LA-EP2006 s.c. post chemotherapy application. LA-EP2006: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.	During each chemotherapy cycle eligible patients receive Neulasta® s.c. post chemotherapy application. Neulasta®: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.
Measure Participants	159	157
Yes	0 0%	2 1.3%
No	159 100%	155 98.7%

Adverse Events

Time Frame	Patients were followed for a 6-month safety period from the last administration of pegfilgrastim.
Adverse Event Reporting Description	If not otherwise specified, only treatment-emergent adverse event (TEAEs) (i.e. AEs with a date of onset on or after the date of the first administration of chemotherapy and not later than 30 days after the last dose of chemotherapy) and post-TEAEs (i.e. AEs with a date of onset after the time point of 30 days after the last chemotherapy administration) are reported. SAF set = safety analysis set was used
Arm/Group Title	LA-EP2006		Neulasta®
Arm/Group Description	During each chemotherapy cycle eligible patients receive LA-EP2006 s.c. post chemotherapy application. LA-EP2006: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.		During each chemotherapy cycle eligible patients receive Neulasta® s.c. post chemotherapy application. Neulasta®: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.
All Cause Mortality
	LA-EP2006		Neulasta®
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/159 (2.5%)		2/157 (1.3%)
Serious Adverse Events
	LA-EP2006		Neulasta®
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/159 (10.1%)		21/157 (13.4%)
Blood and lymphatic system disorders
Febrile neutropenia	9/159 (5.7%)		12/157 (7.6%)
Neutropenia	3/159 (1.9%)		6/157 (3.8%)
Anemia	1/159 (0.6%)		2/157 (1.3%)
Leukopenia	0/159 (0%)		1/157 (0.6%)
Pancytopenia	0/159 (0%)		1/157 (0.6%)
Thrombocytopenia	0/159 (0%)		1/157 (0.6%)
Cardiac disorders
Cardio-respiratory arrest	2/159 (1.3%)		0/157 (0%)
Cardiac arrest	1/159 (0.6%)		0/157 (0%)
Gastrointestinal disorders
Diarrhea	0/159 (0%)		1/157 (0.6%)
Gastritis	1/159 (0.6%)		0/157 (0%)
Nausea	1/159 (0.6%)		0/157 (0%)
Vomiting	0/159 (0%)		1/157 (0.6%)
General disorders
Pyrexia	1/159 (0.6%)		1/157 (0.6%)
Asthenia	1/159 (0.6%)		0/157 (0%)
Disease progression	0/159 (0%)		1/157 (0.6%)
Fatigue	0/159 (0%)		1/157 (0.6%)
Infections and infestations
Neutropenic sepsis	2/159 (1.3%)		0/157 (0%)
Cellulitis	1/159 (0.6%)		0/157 (0%)
Diverticulitis	1/159 (0.6%)		0/157 (0%)
Gastroenteritis	1/159 (0.6%)		0/157 (0%)
Lower respiratory tract infection	0/159 (0%)		1/157 (0.6%)
Pneumonia bacterial	0/159 (0%)		1/157 (0.6%)
Metabolism and nutrition disorders
Hypoglycemia	1/159 (0.6%)		0/157 (0%)
Musculoskeletal and connective tissue disorders
Myalgia	1/159 (0.6%)		0/157 (0%)
Nervous system disorders
Dizziness	1/159 (0.6%)		0/157 (0%)
Psychiatric disorders
Delirium febrile	1/159 (0.6%)		0/157 (0%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	0/159 (0%)		1/157 (0.6%)
Vascular disorders
Phlebitis	0/159 (0%)		1/157 (0.6%)
Thrombophlebitis	1/159 (0.6%)		0/157 (0%)
Venous thrombosis	1/159 (0.6%)		0/157 (0%)
Other (Not Including Serious) Adverse Events
	LA-EP2006		Neulasta®
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	140/159 (88.1%)		128/157 (81.5%)
Blood and lymphatic system disorders
Neutropenia	25/159 (15.7%)		30/157 (19.1%)
Anemia	16/159 (10.1%)		17/157 (10.8%)
Leukopenia	11/159 (6.9%)		12/157 (7.6%)
Thrombocytopenia	11/159 (6.9%)		10/157 (6.4%)
Cardiac disorders
Cardiac disorders	1/159 (0.6%)		5/157 (3.2%)
Gastrointestinal disorders
Nausea	64/159 (40.3%)		58/157 (36.9%)
Vomitting	34/159 (21.4%)		32/157 (20.4%)
Diarrhoe	23/159 (14.5%)		31/157 (19.7%)
Stomatitis	8/159 (5%)		13/157 (8.3%)
Constipation	10/159 (6.3%)		9/157 (5.7%)
Abdominal pain	8/159 (5%)		7/157 (4.5%)
General disorders
Asthenia	63/159 (39.6%)		56/157 (35.7%)
Fatigue	18/159 (11.3%)		21/157 (13.4%)
Pyrexia	9/159 (5.7%)		12/157 (7.6%)
Pain	7/159 (4.4%)		10/157 (6.4%)
Odema peripheral	10/159 (6.3%)		5/157 (3.2%)
Infections and infestations
Respiratory tract infection viral	3/159 (1.9%)		9/157 (5.7%)
Respiratory tract infection	5/159 (3.1%)		2/157 (1.3%)
Injury, poisoning and procedural complications
Injury, poisoning and procedural complications	1/159 (0.6%)		5/157 (3.2%)
Investigations
Alanine aminotransferase increased	6/159 (3.8%)		3/157 (1.9%)
Aspatate aminotransferase increased	6/159 (3.8%)		2/157 (1.3%)
Weight decreased	3/159 (1.9%)		5/157 (3.2%)
Gamma-glutamyltransferase increased	2/159 (1.3%)		5/157 (3.2%)
Metabolism and nutrition disorders
Decreased appetite	7/159 (4.4%)		16/157 (10.2%)
Hyperglycaemia	3/159 (1.9%)		8/157 (5.1%)
Musculoskeletal and connective tissue disorders
Arthralgia	10/159 (6.3%)		13/157 (8.3%)
Myalgia	8/159 (5%)		13/157 (8.3%)
Bone pain	7/159 (4.4%)		8/157 (5.1%)
Pain in extremity	6/159 (3.8%)		6/157 (3.8%)
Back pain	1/159 (0.6%)		5/157 (3.2%)
Nervous system disorders
Headache	5/159 (3.1%)		9/157 (5.7%)
Respiratory, thoracic and mediastinal disorders
Cough	4/159 (2.5%)		6/157 (3.8%)
Skin and subcutaneous tissue disorders
Alopecia	82/159 (51.6%)		79/157 (50.3%)
Erythema	14/159 (8.8%)		16/157 (10.2%)
Vascular disorders
Vascular disorders	9/159 (5.7%)		10/157 (6.4%)

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.