Randomized Phase 2, Dose-finding Efficacy, Safety Study of ANF-RHO™ Versus Neulasta® in Chemotherapy-Induced Neutropenia

Phase 2TerminatedNCT03559387

Prolong Pharmaceuticals9 enrolled

Overview

Randomized, Open-Label study to determine the dose, efficacy, safety and pharmacokinetic profile of ANF-RHO™ with once-per-cycle injection in comparison with Neulasta in Breast Cancer patients at high risk of developing Chemotherapy-Induced Neutropenia

Forty Eight (48) adult female, chemotherapy treatment-naïve, stage I to III, breast cancer patients scheduled to receive FEC100 (3 cycles)/docetaxel (3 cycles) myelosuppressive chemotherapy will be enrolled into the study after they meet all the inclusion/exclusion criteria. Four (4) Cohorts of 12 patients each will be studied; they will be randomized either in the ANF-RHO™ treatment arm at different doses (10 μg/kg, 20 μg/kg, or 30 μg/kg, for the cohorts 1-3, respectively) or Neulasta® (6 mg / 0.6 ml SC injection, for cohort 4). For the cohorts 1-3, 12 patients from each of the respective ANF-RHO™ cohorts will be randomized with four patients from cohort 4 (Neulasta®). Patients in the ANF-RHO™ cohorts will receive study drug on Day 1 of each Chemotherapy cycle. Patients in the Neulasta® cohort will receive study drug on Day 2 of each Chemotherapy cycle. Doses of ANF-RHO™/Neulasta® will be provided for a total of 6 cycles (21 days each). The total duration of the study 129 ± 2 days (126 Days of treatment period followed by end of study visit)

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Chemotherapy-induced Neutropenia

Interventions

ANF-RHO™DRUG

Subjects randomized to the ANF-RHO™ treatment arm will receive the investigational product on Day 1(day of chemotherapy treatment) of each Chemotherapy cycle. ANF-RHO™ will be administered to the subjects as a subcutaneous injection. Subjects will receive the ANF-RHO™ dose with a volume equivalent to 10 µg/kg, 20 µg/kg and 30 µg/kg. ANF-RHO™ is provided as a single-use glass vial containing 1.0 ml of solution at a concentration of 5 mg/ml

Neulasta®DRUG

Subjects randomized to the Neulasta® treatment arm will receive the comparator drug on Day 2(day after chemotherapy treatment) of each Chemotherapy cycle. Neulasta® will be administered to the subjects at a standard dose of 6.0 mg in 0.6 ml as a subcutaneous injection. Neulasta® is also provided as a single-use pre-filled syringe.

Eligibility

Sex: FEMALEMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Adult female patients, 18 years of age or older 2. Signed and dated written consent/assent by the patient or legally authorized representative 3. Histologically confirmed non-metastatic breast cancer 4. ECOG performance status ≤ 2 5. Myelosuppressive chemotherapy naive 6. Scheduled to receive and anticipated to complete the following chemotherapy regimen 1. FEC (fluorouracil/epirubicin (100) / cyclophosphamide) (3 cycles); 2. Docetaxel (3 cycles) chemotherapy 7. White blood cells (WBC) ≥ 3 × 10\^9/L; Absolute neutrophil count (ANC) ≥ 2.0 × 10\^9/L; platelet count ≥ 100 × 10\^9/L; and hemoglobin ≥ 10 g/dL (6.2 mmol/L) 8. Adequate cardiac function (e.g. LVEF \> 50% as determined by standard care) and adequate hepatic function (e.g. liver transaminases \< 2.5 x ULN) 9. Women of childbearing potential with a negative serum pregnancy test and using a highly effective method of birth control (i.e. one that results in a less than 1% per year failure rate when used consistently and correctly, such as implants, injectables, combined oral contraceptives and intrauterine devices (IUDs)). Periodic abstinence is not an acceptable contraceptive method during the study period. Exclusion Criteria: A subject will not be enrolled if any they meet any of the following criteria: 1. Known hypersensitivity to E.coli derived products or polyethylene glycol 2. No other malignancy except carcinoma in situ and basal-cell and squamous cell carcinoma of the skin, unless the other malignancy was treated ≥ 5 years ago with curative intent 3. Evidence of myelodysplasia, aplastic anemia, myelofibrosis, rheumatoid arthritis, systemic lupus erythematosus, or sickle cell disease 4. Clinical diagnosis or history of chronic infection such as hepatitis B virus (HBV), hepatitis C virus (HCV) or Human immunodeficiency virus (HIV) or history of tuberculosis 5. Previous exposure to filgrastim, perfilgrastim or lipegfilgrastim within 30 days before randomization 6. Treatment with systemically active antibiotics within 72 hours before chemotherapy 7. Chronic use of oral corticosteroids 8. Participation in a pharmacological clinical trial within 30 days before randomization 9. Clinical diagnosis of drug abuse or substance abuse within 30 days prior to screening 10. Documented alcohol abuse within 30 days prior to screening 11. Unwilling and/or not capable of ensuring compliance with the provisions of the study protocol 12. Pregnant or breastfeeding women where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive serum HCG laboratory test 13. Other serious medical condition that would prevent individual from receiving protocol treatment

Locations (8)

Hôpital Saint Louis - Center des Maladies du Sein

Paris, France

Institut de cancérologie Jean Godinot

Reims, France

Strasbourg Oncologie Libérale

Strasbourg, France

CHU de Tours

Tours, France

Outcomes

Primary Outcomes

Duration of neutropenia grade 1 or worse (absolute neutrophil count [ANC] ≤ 2.0 x 10^9/L) in the first cycle of chemotherapy (FE100C).

Time frame: 21 days

Secondary Outcomes

Duration of neutropenia grade 1 or worse (absolute neutrophil count [ANC] ≤ 2.0 x 10^9/L) in the fourth cycle of chemotherapy (docetaxel).

Time frame: 21 days

Duration of severe neutropenia (ANC < 0.5 x 10^9/L) during the first chemotherapy cycle (21-day cycle FE100C)

Time frame: 21 days

Duration of severe neutropenia (ANC < 0.5 x 10^9/L) during the fourth chemotherapy cycle (21-day cycle docetaxel)

Time frame: 21 days

Incidence of severe neutropenia (ANC < 0.5 x 10^9/L) during all chemotherapy cycles

Time frame: ~ 128 ± 2 days

Incidence and duration of febrile neutropenia defined as peak temperature ≥38.5°C and ANC < 0.5 x 10^9/L, during all chemotherapy cycles

Time frame: ~ 128 ± 2 days

Incidence and duration of febrile neutropenia defined as peak temperature ≥38.0°C for two readings over two hours and ANC < 0.5 x 10^9/L, during all chemotherapy cycles

Time frame: ~ 128 ± 2 days

Incidence and duration of infection and infection-related events based on use of antibiotics during all chemotherapy cycles

Time frame: ~ 128 ± 2 days

Incidence and duration of infection and infection-related events based on the need for hospitalization during all chemotherapy cycles

Data from ClinicalTrials.gov

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