Study of safety and efficacy of USV Pegfilgrastim and Neulasta® licensed/authorized in EU in patients with breast cancer

• Register: EUCTR
• Last refreshed on: 3 July 2017
• Main ID: EUCTR2015-000266-64-HU
• Date of registration: 04/05/2015
• Prospective Registration: Yes
• Primary sponsor: USV Limited
• Public title: Study of safety and efficacy of USV Pegfilgrastim and Neulasta® licensed/authorized in EU in patients with breast cancer
• Scientific title: A Randomised, Multi-Centre, Assessor-Blinded, Active-Controlled, Parallel Group, Equivalence Phase III Study Comparing the Safety and Efficacy of USV Pegfilgrastim and Neulasta® in Breast Cancer Patients Undergoing Myelosuppressive Chemotherapy
• Date of first enrolment: 18/06/2015
• Target sample size: 255
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-000266-64
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: yes Double blind: no Parallel group: yes Cross over: no Other: yes Other trial design description: Assessor-blinded If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Bosnia and Herzegovina, Bulgaria, Egypt, Georgia, Hungary, Poland, Romania, Russian Federation, Serbia, Turkey, Ukraine

Contacts

• Name: Clinical Trials Info
• Affiliation: Accelsiors CRO and Consultancy Services Ltd

• Name: Clinical Trials Info
• Affiliation: Accelsiors CRO and Consultancy Services Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
1. Written and informed consent before any study procedure is started;
2. Women = 18 years of age;
3. Body weight within 40 and 120 kg;
4. Chemotherapy-naïve subjects with histologically proven breast cancer (Stage IIA, IIB, or IIIA) eligible for six chemotherapy cycles with TAC regimen as an adjuvant treatment;
5. Subjects within 60 days of complete surgical resection of the primary breast tumour: either lumpectomy or mastectomy with sentinel lymph node biopsy or axillary dissection, with clear margins for both invasive and ductal carcinoma in situ (DCIS);
6. Baseline bilateral mammography or other scan to exclude cancer on the contralateral breast;
7. Estimated life expectancy of more than six months;
8. Eastern cooperative oncology group (ECOG) performance status = 2;
9. Normal cardiac function evidenced by a left ventricle ejection fraction (LVEF) >=50% on echocardiogram performed within 60 days from surgery;
10. Adequate bone marrow function prior to chemotherapy administration as indicated by:
a. Leukocyte count < 50 × 109/L,
b. ANC = 1.5 × 109/L,
c. Platelet count = 100 × 109/L, and
d. Haemoglobin (Hb) = 10 g/dL.
11. Appropriate liver and renal functions:
a. Serum bilirubin =< ULN, AST =< 1.5X ULN and, ALT =< 1.5 X ULN concomitant with alkaline phosphatase =< 2.5 X ULN
b. Serum creatinine =< 1.5 ULN
12. All women of childbearing potential, should have a negative serum pregnancy test within one week prior to randomisation and should be using or willing to use a highly effective method of birth control diaphragm, condom (by the partner), copper intrauterine device (or hormonal), sponge, or spermicide, and hormonal contraceptives. Appropriate hormonal contraceptives will include any registered and marketed contraceptive agent that contains an estrogen and/or a progestational agent (including oral, s.c., intrauterine, or intramuscular agents). Reliable contraception should be maintained from four weeks prior to first dose and throughout the whole study.
13. Willing and able to undergo procedures required by this protocol.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 220
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 35

Exclusion criteria:
1. Subjects with distant metastasis;
2. Subjects with severe chronic neutropenia (congenital, cyclic, or idiopathic);
3. History of chronic myeloid leukaemia or myelodysplastic syndrome;
4. History of sickle cell disease;
5. Subjects with active infections (including positive serology for human immunodeficiency virus [HIV] and active hepatitis B and C infection). Subjects with infections bacterial or fungal not controlled by antibiotic therapy; or history of uncontrolled seizures, or diabetes, or central nervous system disorders should be excluded as per the clinical judgement of the investigator precluding informed consent;
6. Previous or concurrent malignancy except non-invasive skin cancer (excluding melanoma), in situ carcinoma of the cervix, or other solid tumour treated with curative intent with no recurrence within two years prior to study entry;
7. Hormonal therapy (e.g. tamoxifen or aromatase inhibitors), immunotherapy and monoclonal antibodies or biological therapy concurrent or within 30 days of screening;
8. Significant neurologic or psychiatric disorders that would prohibit the understanding and giving of the informed consent;
9. Previous therapy with any recombinant human granulocyte colony stimulating factor (rhG-CSF) product, Lipegfilgrastim, or Pegfilgrastim preparation;
10. Concurrent radiotherapy;
11. Clinically significant cardiac dysfunction at the time of screening, history of myocardial infarction, heart failure, uncontrolled hypertension, severe valvular heart disease, unstable angina pectoris, pericardial disease, electrocardiographic evidence of acute ischemic changes or unstable arrhythmia within six months preceding the first treatment cycle;
12. History of pulmonary infiltrates or pneumonia within two years of study entry;
13. Known hypersensitivity to any of the chemotherapy drugs used in TAC regime or Escherichia coli (E. coli) proteins or any of the excipients used in the IMP;
14. Major organ allograft or condition requiring chronic immunosuppression (i.e. kidney, liver, lung, heart, bone marrow transplant, or autoimmune diseases). Subjects who received corneal transplants or cadaver skin or bone transplants are eligible;
15. Peripheral neuropathy >Grade 1;
16. Ongoing drug abuse and/or alcohol addiction and/or chronic alcoholism;
17. Participation in any other clinical study using an IMP within three months prior to the screening visit;
18. Pregnancy or breast feeding;
19. Any condition that by consideration of the investigators might affect the safety of the subject or interfere with the efficacy assessments of this study.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: no

Health Condition(s) or Problem(s) studied

Duration of Sever Neutropenia and incidence of febrile neutropenia
MedDRA version: 18.0 Level: PT Classification code 10029354 Term: Neutropenia System Organ Class: 10005329 - Blood and lymphatic system disorders
MedDRA version: 18.0 Level: PT Classification code 10016288 Term: Febrile neutropenia System Organ Class: 10005329 - Blood and lymphatic system disorders

Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

Intervention(s)

Product Name: USV Pegfilgrastim
Product Code: USV Pegfilgrastim
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: PEGFILGRASTIM
CAS Number: 208265-92-3
Current Sponsor code: USV Pegfilgrastim
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Trade Name: Neulasta
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: PEGFILGRASTIM
CAS Number: 208265-92-3
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Primary Outcome(s)

Main Objective: To assess the efficacy of USV Pegfilgrastim compared to Neulasta® with respect to the mean duration of severe neutropenia (DSN) defined as the mean number of days with Grade 4 neutropenia [absolute neutrophil count (ANC) less than 0.5 × 109/L], during Cycle 1 of the chemotherapy treatment.

Primary end point(s): Mean duration of severe neutropenia (Grade 4), defined as the number of days in which the subject has an ANC < 0.5 × 109/L during Cycle 1 of chemotherapy.

Secondary Objective: To further compare USV Pegfilgrastim and Neulasta® with respect to the efficacy, safety, and immunogenicity of both products.

Timepoint(s) of evaluation of this end point: Cycle 1

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Cycles 1-6 and six months follow up period

Secondary end point(s): Secondary efficacy endpoints:
•Mean duration of severe neutropenia (DSN) during cycles 2 to 6;
•Depth of ANC nadir, defined as the subject’s lowest ANC in Cycles 1 to 6;
•The number and proportion of subjects with febrile neutropenia episodes defined as single temperature: =38,3°C measured orally or =38,0°C for over 1 hour; neutropenia: ANC <0,5 X 109/L or <1 X 109/L and a predicted decline to =0,5 X 109/L over the next 48 hours (ANC and temperature measured on the same day) in all cycles;
•Time to neutrophil recovery, defined as the time in days from the chemotherapy administration until the subject’s ANC increases to > 2.0 × 109/L after the nadir in Cycle 1;
•The number and proportion of subjects hospitalised, duration of hospitalisations and time in intensive care unit (ICU) due to neutropenia complications by cycle;
•The number and proportion of subjects with clinically documented infections by cycle;
•Use of intravenous (i.v.) antibiotics during each cycle.
Safety Endpoints:
•Probability of occurrence, and severity of the most common adverse events (AEs) associated with Pegfilgrastim treatment;
•Bone pain;
•Probability of occurrence, and severity of other AEs including mortality during treatment for any cause;
•Assessment of local tolerability at the injection site(s);
•Systemic tolerance (physical examination, vital signs, and laboratory assessments of safety parameters);
•Immunogenicity assessments up to six months after the last dose of the IMP.

Secondary ID(s)

PEGF/USV/P3/003

Source(s) of Monetary Support

USV Limited