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

Primary Purpose

Neutropenic Complications, Breast Neoplasms, Chemotherapy-induced Neutropenia

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 Neutropenic Complications focused on measuring biosimilars, Pegfilgrastim,, G-CSF,, neutropenia,, breast cancer,, myelosuppressive chemotherapy,, supportive care, granulocyte-colony-stimulating factor

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

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Neulasta®

LA-EP2006

Arm Description

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

During each chemotherapy cycle eligible patients receive LA-EP2006 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 cells/L (grade 4 neutropenia).

Secondary Outcome Measures

Incidence of Febrile Neutropenia (FN)
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.
Number of Patients With at Least One Episode of Fever by Cycle and Across All Cycles
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.
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. Only the evaluable patients with a depth of ANC in Cycle 1 are given.
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 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.
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
November 22, 2012
Last Updated
June 29, 2017
Sponsor
Sandoz
Collaborators
Sandoz GmbH
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1. Study Identification

Unique Protocol Identification Number
NCT01735175
Brief Title
Phase III Study Comparing the Efficacy and Safety of LA-EP2006 and Neulasta®
Acronym
PROTECT-1
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 Type
Interventional

2. Study Status

Record Verification Date
June 2017
Overall Recruitment Status
Completed
Study Start Date
June 2012 (undefined)
Primary Completion Date
May 2013 (Actual)
Study Completion Date
February 2014 (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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neutropenic Complications, Breast Neoplasms, Chemotherapy-induced Neutropenia, Chemotherapeutic Toxicity
Keywords
biosimilars, Pegfilgrastim,, G-CSF,, neutropenia,, breast cancer,, myelosuppressive chemotherapy,, supportive care, granulocyte-colony-stimulating factor

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
Neulasta®
Arm Type
Active Comparator
Arm Description
During each chemotherapy cycle eligible patients receive Neulasta® s.c. post chemotherapy application.
Arm Title
LA-EP2006
Arm Type
Experimental
Arm Description
During each chemotherapy cycle eligible patients receive LA-EP2006 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 pegfilgrastim is injected s.c. post chemotherapy application.
Intervention Type
Drug
Intervention Name(s)
Neulasta®
Other Intervention Name(s)
pegfilgrastim
Intervention Description
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.
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 cells/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 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)
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)
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)
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 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)
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 (41 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
Official's Role
Study Chair
Facility Information:
Facility Name
Sandoz Investigational Site
City
Ijui
ZIP/Postal Code
98700-000
Country
Brazil
Facility Name
Sandoz Investigational Site
City
Lajeado
ZIP/Postal Code
95900-000
Country
Brazil
Facility Name
Sandoz Investigational Site
City
Santo Andre
ZIP/Postal Code
0960-650
Country
Brazil
Facility Name
Sandoz Investigational Site
City
Andhra Pradesh
ZIP/Postal Code
530002
Country
India
Facility Name
Sandoz Investigational Site
City
Delhi
ZIP/Postal Code
110095
Country
India
Facility Name
Sandoz Investigational Site
City
Madurai
ZIP/Postal Code
625107
Country
India
Facility Name
Sandoz Investigational Site
City
Maharashtra
ZIP/Postal Code
411001
Country
India
Facility Name
Sandoz Investigational Site
City
Maharashtra
ZIP/Postal Code
416008
Country
India
Facility Name
Sandoz Investigational Site
City
Maharashtra
ZIP/Postal Code
440010
Country
India
Facility Name
Sandoz Investigational Site
City
Mumbai
ZIP/Postal Code
422005
Country
India
Facility Name
Sandoz Investigational Site
City
Rajasthan
ZIP/Postal Code
302013
Country
India
Facility Name
Sandoz Investigational Site
City
Aguascalientes
ZIP/Postal Code
20230
Country
Mexico
Facility Name
Sandoz Investigational Site
City
Juchitan
ZIP/Postal Code
70000
Country
Mexico
Facility Name
Sandoz Investigational Site
City
Bucharest
ZIP/Postal Code
11461
Country
Romania
Facility Name
Sandoz Investigational Site
City
Bucharest
ZIP/Postal Code
23423
Country
Romania
Facility Name
Sandoz Investigational Site
City
Iasi
ZIP/Postal Code
700106
Country
Romania
Facility Name
Sandoz Investigational Site
City
Suceava
ZIP/Postal Code
720237
Country
Romania
Facility Name
Sandoz Investigational Site
City
Barnaul
ZIP/Postal Code
656052
Country
Russian Federation
Facility Name
Sandoz Investigational Site
City
Bashkortostan
ZIP/Postal Code
450054
Country
Russian Federation
Facility Name
Sandoz Investigational Site
City
Berdsk
ZIP/Postal Code
633004
Country
Russian Federation
Facility Name
Sandoz Investigational Site
City
Ivanovo
ZIP/Postal Code
153040
Country
Russian Federation
Facility Name
Sandoz Investigational Site
City
Kabardino
ZIP/Postal Code
361045
Country
Russian Federation
Facility Name
Sandoz Investigational Site
City
Kazan
ZIP/Postal Code
420029
Country
Russian Federation
Facility Name
Sandoz Investigational Site
City
Krasnodar
ZIP/Postal Code
354057
Country
Russian Federation
Facility Name
Sandoz Investigational Site
City
Kursk
ZIP/Postal Code
305035
Country
Russian Federation
Facility Name
Sandoz Investigational Site
City
Leningrad
ZIP/Postal Code
188663
Country
Russian Federation
Facility Name
Sandoz Investigational Site
City
Moscow
ZIP/Postal Code
115478
Country
Russian Federation
Facility Name
Sandoz Investigational Site
City
Novgorod
ZIP/Postal Code
173016
Country
Russian Federation
Facility Name
Sandoz Investigational Site
City
Oktyabrskaya
ZIP/Postal Code
355047
Country
Russian Federation
Facility Name
Sandoz Investigational Site
City
Ryazan
ZIP/Postal Code
390011
Country
Russian Federation
Facility Name
Sandoz Investigational Site
City
St. Petersburg
ZIP/Postal Code
195067
Country
Russian Federation
Facility Name
Sandoz Investigational Site
City
Tula
ZIP/Postal Code
300053
Country
Russian Federation
Facility Name
Sandoz Investigational Site
City
Cherkasy
ZIP/Postal Code
18009
Country
Ukraine
Facility Name
Sandoz Investigational Site
City
Chernivtsi
ZIP/Postal Code
58013
Country
Ukraine
Facility Name
Sandoz Investigational Site
City
Dnipropetrovsk
ZIP/Postal Code
49102
Country
Ukraine
Facility Name
Sandoz Investigational Site
City
Kharkiv
ZIP/Postal Code
61176
Country
Ukraine
Facility Name
Sandoz Investigational Site
City
Kriviy Rig
ZIP/Postal Code
50048
Country
Ukraine
Facility Name
Sandoz Investigational Site
City
Lugansk
ZIP/Postal Code
91000
Country
Ukraine
Facility Name
Sandoz Investigational Site
City
Mariupol
ZIP/Postal Code
87500
Country
Ukraine
Facility Name
Sandoz Investigational Site
City
Vinnytsya
ZIP/Postal Code
21029
Country
Ukraine
Facility Name
Sandoz Investigational Site
City
Zaporizhzhia
ZIP/Postal Code
69040
Country
Ukraine

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
27020170
Citation
Harbeck N, Lipatov O, Frolova M, Udovitsa D, Topuzov E, Ganea-Motan DE, Nakov R, Singh P, Rudy A, Blackwell K. Randomized, double-blind study comparing proposed biosimilar LA-EP2006 with reference pegfilgrastim in breast cancer. Future Oncol. 2016 Jun;12(11):1359-67. doi: 10.2217/fon-2016-0016. Epub 2016 Mar 29.
Results Reference
result
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 Neulasta®

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