Neutropenic ComplicationsPhase 3PROTECT-1NCT01735175

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

A Phase 3 study testing LA-EP2006 and Neulasta® in people with Neutropenic Complications and Breast Neoplasms, run by Sandoz at 41 sites in 6 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 years and older, women only
Conditions the study is for: Neutropenic Complications, Breast Neoplasms, Chemotherapy-induced Neutropenia
What is being tested?: LA-EP2006 and Neulasta®
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 316 participants
Where: 41 sitesin 6 countries
Study dates: Jun 2012to Feb 2014
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
Women only
No healthy volunteers
Adult, Older adult

Who may be able to join

histologically proven breast cancer
eligible for six cycles of neoadjuvant or adjuvant chemotherapy

Who cannot join

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.

Trial locations and contacts

41 sites in 6 countries.

Country

City, postcode or hospital

41 sites in 6 countries

Russia15 sites

Sandoz Investigational Site
Barnaul, 656052
Sandoz Investigational Site
Bashkortostan, 450054
Sandoz Investigational Site
Berdsk, 633004
Sandoz Investigational Site
Ivanovo, 153040
Sandoz Investigational Site
Kabardino, 361045
Sandoz Investigational Site
Kazan', 420029
Sandoz Investigational Site
Krasnodar, 354057
Sandoz Investigational Site
Kursk, 305035
Sandoz Investigational Site
Moscow, 115478
Sandoz Investigational Site
Oktyabrskaya, 355047
Sandoz Investigational Site
Ryazan, 390011
Sandoz Investigational Site
Saint Petersburg, 188663
Sandoz Investigational Site
Saint Petersburg, 195067
Sandoz Investigational Site
Tula, 300053
Sandoz Investigational Site
Velikiy Novgorod, 173016

Other trials in Russia

Ukraine9 sites

Sandoz Investigational Site
Cherkasy, 18009
Sandoz Investigational Site
Chernivtsi, 58013
Sandoz Investigational Site
Dnipropetrovsk, 49102
Sandoz Investigational Site
Kharkiv, 61176
Sandoz Investigational Site
Kryvyi Rih, 50048
Sandoz Investigational Site
Luhansk, 91000
Sandoz Investigational Site
Mariupol, 87500
Sandoz Investigational Site
Vinnytsia, 21029
Sandoz Investigational Site
Zaporizhzhya, 69040

Other trials in Ukraine

India8 sites

Sandoz Investigational Site
Andhra Pradesh, 530002
Sandoz Investigational Site
Delhi, 110095
Sandoz Investigational Site
Madurai, 625107
Sandoz Investigational Site
Maharashtra, 411001
Sandoz Investigational Site
Maharashtra, 416008
Sandoz Investigational Site
Maharashtra, 440010
Sandoz Investigational Site
Mumbai, 422005
Sandoz Investigational Site
Rajasthan, 302013

Other trials in India

Romania4 sites

Sandoz Investigational Site
Bucharest, 11461
Sandoz Investigational Site
Bucharest, 23423
Sandoz Investigational Site
Iași, 700106
Sandoz Investigational Site
Suceava, 720237

Other trials in Romania

Brazil3 sites

Sandoz Investigational Site
Ijuí, 98700-000
Sandoz Investigational Site
Lajeado, 95900-000
Sandoz Investigational Site
Santo André, 0960-650

Other trials in Brazil

Mexico2 sites

Sandoz Investigational Site
Aguascalientes, 20230
Sandoz Investigational Site
Juchitán, 70000

Other trials in Mexico

About this study

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

Read the 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.

Conditions: Neutropenic Complications, Breast Neoplasms, Chemotherapy-induced Neutropenia, Chemotherapeutic Toxicity
Being tested: LA-EP2006, Neulasta®
Keywords: biosimilars, Pegfilgrastim,, G-CSF,, neutropenia,, breast cancer,, myelosuppressive chemotherapy,, supportive care, granulocyte-colony-stimulating factor
Medical subject headings: Breast Neoplasms, Neutropenia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

LA-EP2006Drug
Also called pegfilgrastim
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.
Neulasta®Drug
Also called pegfilgrastim
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.

Study groups in NCT01735175
Study group	Role	What they receive
Neulasta®	Active comparator	During each chemotherapy cycle eligible patients receive Neulasta® s.c. post chemotherapy application. Receives: Drug: Neulasta®
LA-EP2006	Experimental	During each chemotherapy cycle eligible patients receive LA-EP2006 s.c. post chemotherapy application. Receives: Drug: LA-EP2006

What is being measured

The primary outcome is the main question the study is designed to answer.

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).
Measured: 21 days (Cycle 1 of chemotherapy treatment)

Secondary outcomes (7)

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.
Measured: across all cycles (18 weeks)
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.
Measured: across al cycles (18 weeks)
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.
Measured: Cycle 1 (3 weeks)
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.
Measured: Cycle 1 (3 weeks)
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.
Measured: across Cycle 1 (3 weeks)
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".
Measured: across all cycles (18 weeks)
Mortality Due to Infection
Number of patients with death due to infections
Measured: Study course (41 weeks)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jun 2012Feb 2014

First posted28 Nov 2012 (estimated)
Study startJun 2012
Primary completionMay 2013
Study completionFeb 2014

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Neutropenic ComplicationsStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Supportive care
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 316 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01735175
Sponsor's protocol ID: LA-EP06-301
Other IDs: 2011-004532-58
Acronym: PROTECT-1
Status last verified: Jun 2017
First submitted: 22 Nov 2012
Last updated: 7 Aug 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: Undecided

Publications

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.
PubMed 27020170
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.
PubMed 28637287

Study at a glance

From the registry record, last updated by the sponsor on 7 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT01735175
Acronym / sponsor ID: PROTECT-1 / LA-EP06-301
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
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 316 participants (actual)
Lead sponsor: SandozIndustry (pharma, biotech, devices)
Collaborators: Sandoz GmbH
Study start: Jun 2012
Primary completion: May 2013 (actual)
Study completion: Feb 2014 (actual)
First posted: 28 Nov 2012 (estimated)
Results: Posted 15 Jun 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Supportive care
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Neulasta®	Active comparator	Drug: Neulasta®During each chemotherapy cycle eligible patients receive Neulasta® s.c. post chemotherapy application.
LA-EP2006	Experimental	Drug: LA-EP2006During each chemotherapy cycle eligible patients receive LA-EP2006 s.c. post chemotherapy application.

Who may qualify

Ages: 18 years and older
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (2 listed)

histologically proven breast cancer
eligible for six cycles of neoadjuvant or adjuvant chemotherapy

Key exclusion criteria (5 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
LA-EP2006Also: pegfilgrastimEligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.	Drug	LA-EP2006
Neulasta®Also: pegfilgrastimEligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.	Drug	Neulasta®

Primary outcome

Mean Duration of Severe Neutropenia (DSN) During Cycle 1 of Chemotherapy
Time frame: 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).

7 secondary outcomes

Incidence of Febrile Neutropenia (FN)
Time frame: across all cycles (18 weeks)
Number of Patients With at Least One Episode of Fever by Cycle and Across All Cycles
Time frame: across al cycles (18 weeks)
Depth of ANC Nadir in Cycle 1
Time frame: Cycle 1 (3 weeks)
Number of Patients With ANC Nadir Per Day in Cycle 1
Time frame: Cycle 1 (3 weeks)
Time to ANC Recovery in Days in Cycle 1
Time frame: across Cycle 1 (3 weeks)
Frequency of Infections by Cycle and Across All Cycles
Time frame: across all cycles (18 weeks)
Mortality Due to Infection
Time frame: Study course (41 weeks)

Results and safety

Results posted to the registry on 15 Jun 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
LA-EP2006	159	130
Neulasta®	157	144

Primary outcome: Mean Duration of Severe Neutropenia (DSN) During Cycle 1 of Chemotherapy

Time frame: 21 days (Cycle 1 of chemotherapy treatment). Mean (Standard Deviation). Unit: days

Measure	LA-EP2006 n = 159	Neulasta® n = 157
FAS	0.75 (0.878)	0.83 (0.898)
PP	0.75 (0.875)	0.79 (0.872)

LA-EP2006 vs Neulasta®: Mean Difference (Net): 0.07 (95% CI -0.12 to 0.26), p = 0.05, ANCOVA
LA-EP2006 vs Neulasta®: Mean Difference (Net): 0.07 (95% CI -0.12 to 0.26), p = 0.05, ANCOVA

Population analysed: FAS set = full analysis set; PP set = per protocol set

7 secondary outcomes are reported in the full results.

Adverse events

Time frame: Patients were followed for a 6-month safety period from the last administration of pegfilgrastim.. Other adverse events reported at 3% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
LA-EP2006	16 of 159 (10.1%)	140 of 159 (88.1%)	4 of 159
Neulasta®	21 of 157 (13.4%)	128 of 157 (81.5%)	2 of 157

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 27020170Harbeck 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.
Derived from this study: PubMed 28637287Blackwell 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.
Individual participant dataSharing planned: Undecided

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Sandoz Biopharmaceutical Clinical Development study chair

Sandoz

41 sites in 6 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing LA-EP2006 and Neulasta® in people with Neutropenic Complications and Breast Neoplasms, run by Sandoz at 41 sites in 6 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 41 sites in Russia, Ukraine, India, Romania, Brazil and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Jun 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mean Duration of Severe Neutropenia (DSN) During Cycle 1 of Chemotherapy (time frame: 21 days (Cycle 1 of chemotherapy treatment)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01735175, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Aug 2017.