Clinical trial NCT01735175: Phase III Study Comparing the Efficacy and Safety of LA-EP2006 and Neulasta®
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
Overall status: COMPLETED
Phase: PHASE3
Conditions: 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
Lead sponsor: Sandoz
Sponsor class: INDUSTRY
Collaborators: name: Sandoz GmbH
First posted: 2012-11-28
Enrollment: 316
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: 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.

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 (41 weeks)
Other outcomes:
Locations:
city: Ijui
country: Brazil
facility: Sandoz Investigational Site
city: Lajeado
country: Brazil
facility: Sandoz Investigational Site
city: Santo Andre
country: Brazil
facility: Sandoz Investigational Site
city: Andhra Pradesh
country: India
facility: Sandoz Investigational Site
city: Delhi
country: India
facility: Sandoz Investigational Site
city: Madurai
country: India
facility: Sandoz Investigational Site
city: Maharashtra
country: India
facility: Sandoz Investigational Site
city: Maharashtra
country: India
facility: Sandoz Investigational Site
city: Maharashtra
country: India
facility: Sandoz Investigational Site
city: Mumbai
country: India
facility: Sandoz Investigational Site
city: Rajasthan
country: India
facility: Sandoz Investigational Site
city: Aguascalientes
country: Mexico
facility: Sandoz Investigational Site
city: Juchitan
country: Mexico
facility: Sandoz Investigational Site
city: Bucharest
country: Romania
facility: Sandoz Investigational Site
city: Bucharest
country: Romania
facility: Sandoz Investigational Site
city: Iasi
country: Romania
facility: Sandoz Investigational Site
city: Suceava
country: Romania
facility: Sandoz Investigational Site
city: Barnaul
country: Russian Federation
facility: Sandoz Investigational Site
city: Bashkortostan
country: Russian Federation
facility: Sandoz Investigational Site
city: Berdsk
country: Russian Federation
facility: Sandoz Investigational Site
city: Ivanovo
country: Russian Federation
facility: Sandoz Investigational Site
city: Kabardino
country: Russian Federation
facility: Sandoz Investigational Site
city: Kazan
country: Russian Federation
facility: Sandoz Investigational Site
city: Krasnodar
country: Russian Federation
facility: Sandoz Investigational Site
city: Kursk
country: Russian Federation
facility: Sandoz Investigational Site
city: Leningrad
country: Russian Federation
facility: Sandoz Investigational Site
city: Moscow
country: Russian Federation
facility: Sandoz Investigational Site
city: Novgorod
country: Russian Federation
facility: Sandoz Investigational Site
city: Oktyabrskaya
country: Russian Federation
facility: Sandoz Investigational Site
city: Ryazan
country: Russian Federation
facility: Sandoz Investigational Site
city: St. Petersburg
country: Russian Federation
facility: Sandoz Investigational Site
city: Tula
country: Russian Federation
facility: Sandoz Investigational Site
city: Cherkasy
country: Ukraine
facility: Sandoz Investigational Site
city: Chernivtsi
country: Ukraine
facility: Sandoz Investigational Site
city: Dnipropetrovsk
country: Ukraine
facility: Sandoz Investigational Site
city: Kharkiv
country: Ukraine
facility: Sandoz Investigational Site
city: Kriviy Rig
country: Ukraine
facility: Sandoz Investigational Site
city: Lugansk
country: Ukraine
facility: Sandoz Investigational Site
city: Mariupol
country: Ukraine
facility: Sandoz Investigational Site
city: Vinnytsya
country: Ukraine
facility: Sandoz Investigational Site
city: Zaporizhzhia
country: Ukraine
facility: Sandoz Investigational Site
Study officials:
affiliation: Sandoz
name: Sandoz Biopharmaceutical Clinical Development
role: STUDY_CHAIR
References:
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.
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.