Clinical trial NCT01516736: Phase III Study Comparing the Efficacy and Safety of LA-EP2006 and Peg-Filgrastim
Official title: Pivotal Study in Breast Cancer Patients Investigating Efficacy and Safety of LA-EP2006 and Neulasta®
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chemotherapy-induced Neutropenia
Breast Cancer
Keywords: Pegfilgrastim
G-CSF
neutropenia
breast cancer
myelosuppressive chemotherapy
Lead sponsor: Sandoz
Sponsor class: INDUSTRY
Collaborators: name: Sandoz GmbH
First posted: 2012-01-25
Enrollment: 308
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.

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.

Primary outcomes:
measure: Mean Duration of Severe Neutropenia (DSN) During Cycle 1 of Chemotherapy
timeFrame: 21 days (Cycle 1 of chemotherapy treatment)
Secondary outcomes:
measure: Incidence of Febrile Neutropenia (FN)
timeFrame: across all cycles (18 weeks)
measure: Number of Patients With at Least One Episode of Fever by Cycle and Across All Cycles
timeFrame: across al cycles (18 weeks)
measure: Depth of ANC Nadir in Cycle 1
timeFrame: Cycle 1 (3 weeks)
measure: Number of Patients With ANC Nadir Per Day in Cycle 1
timeFrame: Cycle 1 (3 weeks)
measure: Time to ANC Recovery in Days in Cycle 1
timeFrame: across Cycle 1 (3 weeks)
measure: Frequency of Infections by Cycle and Across All Cycles
timeFrame: across all cycles (18 weeks)
measure: Mortality Due to Infection
timeFrame: Study course (19 weeks)
Other outcomes:
Locations:
city: Hot Springs
country: United States
facility: Sandoz Investigational Site
state: Arkansas
city: Jonesboro
country: United States
facility: Sandoz Investigational Site
state: Arkansas
city: Corona
country: United States
facility: Sandoz Investigational Site
state: California
city: Wichita
country: United States
facility: Sandoz Investigational Site
state: Kansas
city: Mount Sterling
country: United States
facility: Sandoz Investigational Site
state: Kentucky
city: Detroit
country: United States
facility: Sandoz Investigational Site
state: Michigan
city: Bismarck
country: United States
facility: Sandoz Investigational Site
state: North Dakota
city: Eugene
country: United States
facility: Sandoz Investigational Site
state: Oregon
city: Germantown
country: United States
facility: Sandoz Investigational Site
state: Tennessee
city: Newport News
country: United States
facility: Sandoz Investigational Site
state: Virginia
city: Tucuman
country: Argentina
facility: Sandoz Investigational Site
city: Temuco
country: Chile
facility: Sandoz Investigational Site
city: Chennai
country: India
facility: Sandoz Investigational Site
city: Delhi
country: India
facility: Sandoz Investigational Site
city: Gujarat
country: India
facility: Sandoz Investigational Site
city: Hyderabad
country: India
facility: Sandoz Investigational Site
city: Karamsad
country: India
facility: Sandoz Investigational Site
city: Lucknow
country: India
facility: Sandoz Investigational Site
city: Maharashtra
country: India
facility: Sandoz Investigational Site
city: Mangalore
country: India
facility: Sandoz Investigational Site
city: Mumbai
country: India
facility: Sandoz Investigational Site
city: Pradesh
country: India
facility: Sandoz Investigational Site
city: Surat
country: India
facility: Sandoz Investigational Site
city: Vadodara
country: India
facility: Sandoz Investigational Site
city: Vellore
country: India
facility: Sandoz Investigational Site
city: Visakhapatnam
country: India
facility: Sandoz Investigational Site
city: Kelantan
country: Malaysia
facility: Sandoz Investigational Site
city: Nilai
country: Malaysia
facility: Sandoz Investigational Site
city: Penang
country: Malaysia
facility: Sandoz Investigational Site
city: Penang
country: Malaysia
facility: Sandoz Investigational Site
city: San Juan
country: Puerto Rico
facility: Sandoz Investigational Site
city: San Juan
country: Puerto Rico
facility: Sandoz Investigational Site
city: Arkhangelsk
country: Russian Federation
facility: Sandoz Investigational Site
city: Bashkortostan
country: Russian Federation
facility: Sandoz Investigational Site
city: Bryansk
country: Russian Federation
facility: Sandoz Investigational Site
city: Kazan
country: Russian Federation
facility: Sandoz Investigational Site
city: Krasnoyarsk
country: Russian Federation
facility: Sandoz Investigational Site
city: Moscow
country: Russian Federation
facility: Sandoz Investigational Site
city: Omsk
country: Russian Federation
facility: Sandoz Investigational Site
city: Orel
country: Russian Federation
facility: Sandoz Investigational Site
city: Orenburg
country: Russian Federation
facility: Sandoz Investigational Site
city: Rostov-na-Donu
country: Russian Federation
facility: Sandoz Investigational Site
city: St Petersburg
country: Russian Federation
facility: Sandoz Investigational Site
city: St. Petersburg
country: Russian Federation
facility: Sandoz Investigational Site
city: St. Petersburg
country: Russian Federation
facility: Sandoz Investigational Site
city: St. Petersburg
country: Russian Federation
facility: Sandoz Investigational Site
city: St. Petersburg
country: Russian Federation
facility: Sandoz Investigational Site
city: Tomsk
country: Russian Federation
facility: Sandoz Investigational Site
city: Vladimir
country: Russian Federation
facility: Sandoz Investigational Site
city: Barcelona
country: Spain
facility: Sandoz Investigational Site
city: Madrid
country: Spain
facility: Sandoz Investigational Site
city: Santiago de Compostela
country: Spain
facility: Sandoz Investigational Site
city: Valencia
country: Spain
facility: Sandoz Investigational Site
Study officials:
affiliation: Sandoz Biopharmaceuticals
name: Sandoz Biopharmaceutical Clinical Development
role: STUDY_CHAIR
References:
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.
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.