search
Back to results

Phase III Study Comparing the Efficacy and Safety of LA-EP2006 and Peg-Filgrastim (PROTECT2)

Primary Purpose

Chemotherapy-induced Neutropenia, Breast Cancer

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
LA-EP2006
Neulasta®
Sponsored by
Sandoz
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Chemotherapy-induced Neutropenia focused on measuring Pegfilgrastim, G-CSF, neutropenia, breast cancer, myelosuppressive chemotherapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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.

Sites / Locations

  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site
  • Sandoz Investigational Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

LA-EP2006

Neulasta®

Arm Description

During each chemotherapy cycle eligible patients receive LA-EP2006 s.c. post chemotherapy application.

During each chemotherapy cycle eligible patients receive Neulasta® s.c. post chemotherapy application.

Outcomes

Primary Outcome Measures

Mean Duration of Severe Neutropenia (DSN) During Cycle 1 of Chemotherapy
Mean duration of severe neutropenia, defined as number of consecutive days with ANC <0.5 × 10^9/l (grade 4 neutropenia).

Secondary Outcome Measures

Incidence of Febrile Neutropenia (FN)
FN was defined as 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.
Number of Patients With at Least One Episode of Fever by Cycle and Across All Cycles
Fever was defined as an oral body temperature of ≥ 38.3°C. Fever episodes were described by maximum oral temperature and the number of patients who had fever at least once.
Depth of ANC Nadir in Cycle 1
The depth of ANC nadir was defined as the patient's lowest ANC (10^9 cells/L) in Cycle 1.
Number of Patients With ANC Nadir Per Day in Cycle 1
Numbers of patients with ANC nadir based per day during Cycle 1 are given.
Time to ANC Recovery in Days in Cycle 1
Time to absolute neutrophil count (ANC) recovery was defined as the time in days from ANC nadir until the patient's ANC had increased to ≥ 2 × 10^9 cells/L after the nadir in Cycle 1.
Frequency of Infections by Cycle and Across All Cycles
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".
Mortality Due to Infection
Number of patients with death due to infections

Full Information

First Posted
January 13, 2012
Last Updated
August 1, 2017
Sponsor
Sandoz
Collaborators
Sandoz GmbH
search

1. Study Identification

Unique Protocol Identification Number
NCT01516736
Brief Title
Phase III Study Comparing the Efficacy and Safety of LA-EP2006 and Peg-Filgrastim
Acronym
PROTECT2
Official Title
Pivotal Study in Breast Cancer Patients Investigating Efficacy and Safety of LA-EP2006 and Neulasta®
Study Type
Interventional

2. Study Status

Record Verification Date
August 2017
Overall Recruitment Status
Completed
Study Start Date
March 2012 (undefined)
Primary Completion Date
August 2013 (Actual)
Study Completion Date
December 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sandoz
Collaborators
Sandoz GmbH

4. Oversight

Data Monitoring Committee
Yes

5. 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.
Detailed Description
The Pegfilgrastim Randomized Oncology (Supportive Care) Trial to Evaluate Comparative Treatment (PROTECT-2) was a confirmatory efficacy and safety study designed to compare the proposed biosimilar LA-EP2006 with the reference pegfilgrastim in woman with early stage breast cancer receiving (neo)-adjuvant myelosuppressive chemotherapy. Patient received TAC (intravenous docetaxel 75mg/m^2, doxorubicin 50 mg/m^2, and cyclophosphamide 500mg/m^2) on day1 of each cycle, for six or more cycles. A total of 308 patients were randomized to LA-EP2006 (n=155) or reference Neulasta® (n=153). Treatment was given subcutaneously on day 2 of each cycle. 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 cells/L). LA-EP2006 was equivalent to the reference product in DSN (difference: -0.16 days; 95% CI [-0.40, 0.08]). Further, LA-EP2006 and the reference pegfilgrastim showed no clinically meaningful differences regarding efficacy and safety.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chemotherapy-induced Neutropenia, Breast Cancer
Keywords
Pegfilgrastim, G-CSF, neutropenia, breast cancer, myelosuppressive chemotherapy

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
308 (Actual)

8. Arms, Groups, and Interventions

Arm Title
LA-EP2006
Arm Type
Experimental
Arm Description
During each chemotherapy cycle eligible patients receive LA-EP2006 s.c. post chemotherapy application.
Arm Title
Neulasta®
Arm Type
Active Comparator
Arm Description
During each chemotherapy cycle eligible patients receive Neulasta® s.c. post chemotherapy application.
Intervention Type
Drug
Intervention Name(s)
LA-EP2006
Other Intervention Name(s)
pegfilgrastim
Intervention Description
Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle LA-EP2006 is injected s.c. post chemotherapy application.
Intervention Type
Drug
Intervention Name(s)
Neulasta®
Other Intervention Name(s)
pegfilgrastim, Neulasta
Intervention Description
Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle Neulasta® is injected s.c. post chemotherapy application.
Primary Outcome Measure Information:
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/l (grade 4 neutropenia).
Time Frame
21 days (Cycle 1 of chemotherapy treatment)
Secondary Outcome Measure Information:
Title
Incidence of Febrile Neutropenia (FN)
Description
FN was defined as 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)
Title
Number of Patients With at Least One Episode of Fever by Cycle and Across All Cycles
Description
Fever was defined as an oral body temperature of ≥ 38.3°C. Fever episodes were described by maximum oral temperature and the number of patients who had fever at least once.
Time Frame
across al cycles (18 weeks)
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.
Time Frame
Cycle 1 (3 weeks)
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)
Title
Time to ANC Recovery in Days in Cycle 1
Description
Time to absolute neutrophil count (ANC) recovery was defined as the time in days from ANC nadir until the patient's ANC had increased to ≥ 2 × 10^9 cells/L after the nadir in Cycle 1.
Time Frame
across Cycle 1 (3 weeks)
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)
Title
Mortality Due to Infection
Description
Number of patients with death due to infections
Time Frame
Study course (19 weeks)

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sandoz Biopharmaceutical Clinical Development
Organizational Affiliation
Sandoz Biopharmaceuticals
Official's Role
Study Chair
Facility Information:
Facility Name
Sandoz Investigational Site
City
Hot Springs
State/Province
Arkansas
ZIP/Postal Code
71913
Country
United States
Facility Name
Sandoz Investigational Site
City
Jonesboro
State/Province
Arkansas
ZIP/Postal Code
72401
Country
United States
Facility Name
Sandoz Investigational Site
City
Corona
State/Province
California
ZIP/Postal Code
92879
Country
United States
Facility Name
Sandoz Investigational Site
City
Wichita
State/Province
Kansas
ZIP/Postal Code
67214
Country
United States
Facility Name
Sandoz Investigational Site
City
Mount Sterling
State/Province
Kentucky
ZIP/Postal Code
40353
Country
United States
Facility Name
Sandoz Investigational Site
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
Sandoz Investigational Site
City
Bismarck
State/Province
North Dakota
ZIP/Postal Code
58501
Country
United States
Facility Name
Sandoz Investigational Site
City
Eugene
State/Province
Oregon
ZIP/Postal Code
97401
Country
United States
Facility Name
Sandoz Investigational Site
City
Germantown
State/Province
Tennessee
ZIP/Postal Code
38138
Country
United States
Facility Name
Sandoz Investigational Site
City
Newport News
State/Province
Virginia
ZIP/Postal Code
23601
Country
United States
Facility Name
Sandoz Investigational Site
City
Tucuman
ZIP/Postal Code
4000
Country
Argentina
Facility Name
Sandoz Investigational Site
City
Temuco
ZIP/Postal Code
4810469
Country
Chile
Facility Name
Sandoz Investigational Site
City
Chennai
ZIP/Postal Code
600031
Country
India
Facility Name
Sandoz Investigational Site
City
Delhi
ZIP/Postal Code
110092
Country
India
Facility Name
Sandoz Investigational Site
City
Gujarat
ZIP/Postal Code
380009
Country
India
Facility Name
Sandoz Investigational Site
City
Hyderabad
ZIP/Postal Code
50024
Country
India
Facility Name
Sandoz Investigational Site
City
Karamsad
ZIP/Postal Code
388325
Country
India
Facility Name
Sandoz Investigational Site
City
Lucknow
ZIP/Postal Code
226003
Country
India
Facility Name
Sandoz Investigational Site
City
Maharashtra
ZIP/Postal Code
422004
Country
India
Facility Name
Sandoz Investigational Site
City
Mangalore
ZIP/Postal Code
575001
Country
India
Facility Name
Sandoz Investigational Site
City
Mumbai
ZIP/Postal Code
400010
Country
India
Facility Name
Sandoz Investigational Site
City
Pradesh
ZIP/Postal Code
520002
Country
India
Facility Name
Sandoz Investigational Site
City
Surat
ZIP/Postal Code
395010
Country
India
Facility Name
Sandoz Investigational Site
City
Vadodara
ZIP/Postal Code
391760
Country
India
Facility Name
Sandoz Investigational Site
City
Vellore
ZIP/Postal Code
632004
Country
India
Facility Name
Sandoz Investigational Site
City
Visakhapatnam
ZIP/Postal Code
530017
Country
India
Facility Name
Sandoz Investigational Site
City
Kelantan
ZIP/Postal Code
16150
Country
Malaysia
Facility Name
Sandoz Investigational Site
City
Nilai
ZIP/Postal Code
71800
Country
Malaysia
Facility Name
Sandoz Investigational Site
City
Penang
ZIP/Postal Code
11200
Country
Malaysia
Facility Name
Sandoz Investigational Site
City
Penang
ZIP/Postal Code
11600
Country
Malaysia
Facility Name
Sandoz Investigational Site
City
San Juan
ZIP/Postal Code
00910
Country
Puerto Rico
Facility Name
Sandoz Investigational Site
City
San Juan
ZIP/Postal Code
00927
Country
Puerto Rico
Facility Name
Sandoz Investigational Site
City
Arkhangelsk
ZIP/Postal Code
163045
Country
Russian Federation
Facility Name
Sandoz Investigational Site
City
Bashkortostan
ZIP/Postal Code
450054
Country
Russian Federation
Facility Name
Sandoz Investigational Site
City
Bryansk
ZIP/Postal Code
241033
Country
Russian Federation
Facility Name
Sandoz Investigational Site
City
Kazan
ZIP/Postal Code
420029
Country
Russian Federation
Facility Name
Sandoz Investigational Site
City
Krasnoyarsk
ZIP/Postal Code
660133
Country
Russian Federation
Facility Name
Sandoz Investigational Site
City
Moscow
ZIP/Postal Code
115478
Country
Russian Federation
Facility Name
Sandoz Investigational Site
City
Omsk
ZIP/Postal Code
644046
Country
Russian Federation
Facility Name
Sandoz Investigational Site
City
Orel
ZIP/Postal Code
302020
Country
Russian Federation
Facility Name
Sandoz Investigational Site
City
Orenburg
ZIP/Postal Code
460021
Country
Russian Federation
Facility Name
Sandoz Investigational Site
City
Rostov-na-Donu
ZIP/Postal Code
344037
Country
Russian Federation
Facility Name
Sandoz Investigational Site
City
St Petersburg
ZIP/Postal Code
197758
Country
Russian Federation
Facility Name
Sandoz Investigational Site
City
St. Petersburg
ZIP/Postal Code
194017
Country
Russian Federation
Facility Name
Sandoz Investigational Site
City
St. Petersburg
ZIP/Postal Code
194044
Country
Russian Federation
Facility Name
Sandoz Investigational Site
City
St. Petersburg
ZIP/Postal Code
195271
Country
Russian Federation
Facility Name
Sandoz Investigational Site
City
St. Petersburg
ZIP/Postal Code
197022
Country
Russian Federation
Facility Name
Sandoz Investigational Site
City
Tomsk
ZIP/Postal Code
634009
Country
Russian Federation
Facility Name
Sandoz Investigational Site
City
Vladimir
ZIP/Postal Code
600021
Country
Russian Federation
Facility Name
Sandoz Investigational Site
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Sandoz Investigational Site
City
Madrid
ZIP/Postal Code
28040
Country
Spain
Facility Name
Sandoz Investigational Site
City
Santiago de Compostela
ZIP/Postal Code
15706
Country
Spain
Facility Name
Sandoz Investigational Site
City
Valencia
ZIP/Postal Code
46014
Country
Spain

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
27091420
Citation
Blackwell K, Donskih R, Jones CM, Nixon A, Vidal MJ, Nakov R, Singh P, Schaffar G, Gascon P, Harbeck N. A Comparison of Proposed Biosimilar LA-EP2006 and Reference Pegfilgrastim for the Prevention of Neutropenia in Patients With Early-Stage Breast Cancer Receiving Myelosuppressive Adjuvant or Neoadjuvant Chemotherapy: Pegfilgrastim Randomized Oncology (Supportive Care) Trial to Evaluate Comparative Treatment (PROTECT-2), a Phase III, Randomized, Double-Blind Trial. Oncologist. 2016 Jul;21(7):789-94. doi: 10.1634/theoncologist.2016-0011. Epub 2016 Apr 18.
Results Reference
background
PubMed Identifier
28637287
Citation
Blackwell K, Gascon P, Jones CM, Nixon A, Krendyukov A, Nakov R, Li Y, Harbeck N. Pooled analysis of two randomized, double-blind trials comparing proposed biosimilar LA-EP2006 with reference pegfilgrastim in breast cancer. Ann Oncol. 2017 Sep 1;28(9):2272-2277. doi: 10.1093/annonc/mdx303.
Results Reference
derived

Learn more about this trial

Phase III Study Comparing the Efficacy and Safety of LA-EP2006 and Peg-Filgrastim

We'll reach out to this number within 24 hrs