Back to resultsRandomized Phase 2, Dose-finding Efficacy, Safety Study of ANF-RHO™ Versus Neulasta® in Chemotherapy-Induced Neutropenia
Primary Purpose
Chemotherapy-induced Neutropenia
Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
ANF-RHO™
Neulasta®
Sponsored by
About this trial
This is an interventional treatment trial for Chemotherapy-induced Neutropenia
Eligibility Criteria
Inclusion Criteria:
- Adult female patients, 18 years of age or older
- Signed and dated written consent/assent by the patient or legally authorized representative
- Histologically confirmed non-metastatic breast cancer
- ECOG performance status ≤ 2
- Myelosuppressive chemotherapy naive
Scheduled to receive and anticipated to complete the following chemotherapy regimen
- FEC (fluorouracil/epirubicin (100) / cyclophosphamide) (3 cycles);
- Docetaxel (3 cycles) chemotherapy
- 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)
- Adequate cardiac function (e.g. LVEF > 50% as determined by standard care) and adequate hepatic function (e.g. liver transaminases < 2.5 x ULN)
- 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:
- Known hypersensitivity to E.coli derived products or polyethylene glycol
- 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
- Evidence of myelodysplasia, aplastic anemia, myelofibrosis, rheumatoid arthritis, systemic lupus erythematosus, or sickle cell disease
- 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
- Previous exposure to filgrastim, perfilgrastim or lipegfilgrastim within 30 days before randomization
- Treatment with systemically active antibiotics within 72 hours before chemotherapy
- Chronic use of oral corticosteroids
- Participation in a pharmacological clinical trial within 30 days before randomization
- Clinical diagnosis of drug abuse or substance abuse within 30 days prior to screening
- Documented alcohol abuse within 30 days prior to screening
- Unwilling and/or not capable of ensuring compliance with the provisions of the study protocol
- 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
- Other serious medical condition that would prevent individual from receiving protocol treatment
Sites / Locations
- Hôpital Saint Louis - Center des Maladies du Sein
- Institut de cancérologie Jean Godinot
- Strasbourg Oncologie Libérale
- CHU de Tours
- Erasmus Medical Center
- Ikazia Ziekenhuis
- Maasstad Ziekenhuis
- Franciscus Gasthuis & Vlietland
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
ANF-RHO™
Neulasta®
Arm Description
Subjects will receive the ANF-RHO™ dose with a volume equivalent to 10 µg/kg, 20 µg/kg and 30 µg/kg as a subcutaneous injection.
Neulasta® will be administered to the subjects at a dose of 6.0 mg in 0.6 ml as a subcutaneous injection.
Outcomes
Primary Outcome Measures
Duration of neutropenia grade 1 or worse (absolute neutrophil count [ANC] ≤ 2.0 x 10^9/L) in the first cycle of chemotherapy (FE100C).
Secondary Outcome Measures
Duration of neutropenia grade 1 or worse (absolute neutrophil count [ANC] ≤ 2.0 x 10^9/L) in the fourth cycle of chemotherapy (docetaxel).
Duration of severe neutropenia (ANC < 0.5 x 10^9/L) during the first chemotherapy cycle (21-day cycle FE100C)
Duration of severe neutropenia (ANC < 0.5 x 10^9/L) during the fourth chemotherapy cycle (21-day cycle docetaxel)
Incidence of severe neutropenia (ANC < 0.5 x 10^9/L) during all chemotherapy cycles
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
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
Incidence and duration of infection and infection-related events based on use of antibiotics during all chemotherapy cycles
Incidence and duration of infection and infection-related events based on the need for hospitalization during all chemotherapy cycles
Incidence and duration of moderate (ANC ≥ 50 x 10^9/L) leukocytosis during all chemotherapy cycles
Incidence and duration of severe (ANC ≥ 100 x 10^9/L) leukocytosis during all chemotherapy cycles
Clinically meaningful changes in vital signs during all chemotherapy cycles - Assessment of Blood pressure
Assessment of Blood pressure (systolic and diastolic) helps determine the safety of the medications under study - ANF-RHO and Neulasta
Clinically meaningful changes in vital signs during all chemotherapy cycles - Assessment of Heart rate
Assessment of Heart rate helps determine the safety of the medications under study - ANF-RHO and Neulasta
Clinically meaningful changes in vital signs during all chemotherapy cycles - Assessment of Respiratory rate
Assessment of Respiratory rate helps determine the safety of the medications under study - ANF-RHO and Neulasta
Clinically meaningful changes in vital signs during all chemotherapy cycles - Assessment of Body Temperature
Assessment of Respiratory rate helps determine the safety of the medications under study - ANF-RHO and Neulasta
Incidence of bone pain, determined by a numerical rating scale, as well as other reported adverse events
Duration of bone pain, determined by a numerical rating scale, as well as other reported adverse events
Severity of bone pain, determined by a numerical rating scale, as well as other reported adverse events
Site of bone pain, determined by a numerical rating scale, as well as other reported adverse events
Pharmacokinetic profile of ANF-RHO and Neulasta - Measurement of Maximum Plasma Concentration (Cmax)
Cmax is the maximum concentration of the drug (either ANF-RHO or Neulasta) that is achieved after administration of a dose
Pharmacokinetic profile of ANF-RHO and Neulasta - Measurement of Time taken to reach the maximum concentration (Tmax)
Tmax is the time taken to reach the maximum concentration (Cmax) after administration of a dose.
Pharmacokinetic profile of ANF-RHO and Neulasta - Measurement of half-life (T1/2)
T1/2 is the time taken for ANF-RHO and Neulasta to reach half the value of their initial concentrations. T1/2 determination helps in understanding the duration for which ANF-RHO or Neulasta would be active upon administration.
Pharmacokinetic profile of ANF-RHO and Neulasta - Area Under the Curve (AUC[0-t])
AUC[0-t] is an important parameter for determining as to how much of the drug is available in the body after administration of a drug formulation, in this case ANF-RHO vs Neulasta. Understanding the AUC for both these drug formulations will help us to determine the efficacy and safety profiles of these medicines.
Pharmacokinetic profile of ANF-RHO and Neulasta - Area Under the Curve (AUC[0-∞])
Similar to AUC[0-t] which is estimated till time 't', in AUC[0-∞], the estimation is done on the concentration of the drug to an infinite time. Calculation of the AUC[0-∞], helps understand how much of the drug is available in the body at extremely low concentrations, beyond the limits of measurable concentrations.
Pharmacokinetic profile of ANF-RHO and Neulasta - Area Under the Curve (AUC[0-t]/AUC[0-∞])
The parameter AUC[0-t]/AUC[0-∞] is useful to calculate the fraction of the Total AUC that was added due to the extrapolated AUC (AUC[0-∞]). It helps understand if the methods employed for determining the total AUC and drug's availability in the body are correct.
Incidence of anti-drug antibodies to ANF-RHO and Neulasta
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03559387
Brief Title
Randomized Phase 2, Dose-finding Efficacy, Safety Study of ANF-RHO™ Versus Neulasta® in Chemotherapy-Induced Neutropenia
Official Title
A Randomized and Open-label Dose-finding, Ph. 2, Efficacy, Safety, and Pharmacokinetic Study of Once-per-cycle Prophylactic Injections of ANF-RHO™ Versus Pegfilgrastim (Neulasta®) in Non-metastatic Breast Cancer Patients at High-risk of Chemotherapy-induced Neutropenia
Study Type
Interventional
2. Study Status
Record Verification Date
June 2018
Overall Recruitment Status
Terminated
Why Stopped
Study redesign
Study Start Date
August 3, 2017 (Actual)
Primary Completion Date
April 18, 2018 (Actual)
Study Completion Date
May 22, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Prolong Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No
5. Study Description
Brief Summary
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
Detailed Description
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)
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chemotherapy-induced Neutropenia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
9 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ANF-RHO™
Arm Type
Experimental
Arm Description
Subjects will receive the ANF-RHO™ dose with a volume equivalent to 10 µg/kg, 20 µg/kg and 30 µg/kg as a subcutaneous injection.
Arm Title
Neulasta®
Arm Type
Active Comparator
Arm Description
Neulasta® will be administered to the subjects at a dose of 6.0 mg in 0.6 ml as a subcutaneous injection.
Intervention Type
Drug
Intervention Name(s)
ANF-RHO™
Other Intervention Name(s)
Pegylated Granulocyte Colony-Stimulating Factor (PEG-GCSF)
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Neulasta®
Other Intervention Name(s)
Pegylated Granulocyte Colony-Stimulating Factor (PEG-GCSF)
Intervention Description
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.
Primary Outcome Measure Information:
Title
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 Outcome Measure Information:
Title
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
Title
Duration of severe neutropenia (ANC < 0.5 x 10^9/L) during the first chemotherapy cycle (21-day cycle FE100C)
Time Frame
21 days
Title
Duration of severe neutropenia (ANC < 0.5 x 10^9/L) during the fourth chemotherapy cycle (21-day cycle docetaxel)
Time Frame
21 days
Title
Incidence of severe neutropenia (ANC < 0.5 x 10^9/L) during all chemotherapy cycles
Time Frame
~ 128 ± 2 days
Title
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
Title
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
Title
Incidence and duration of infection and infection-related events based on use of antibiotics during all chemotherapy cycles
Time Frame
~ 128 ± 2 days
Title
Incidence and duration of infection and infection-related events based on the need for hospitalization during all chemotherapy cycles
Time Frame
~ 128 ± 2 days
Title
Incidence and duration of moderate (ANC ≥ 50 x 10^9/L) leukocytosis during all chemotherapy cycles
Time Frame
~ 128 ± 2 days
Title
Incidence and duration of severe (ANC ≥ 100 x 10^9/L) leukocytosis during all chemotherapy cycles
Time Frame
~ 128 ± 2 days
Title
Clinically meaningful changes in vital signs during all chemotherapy cycles - Assessment of Blood pressure
Description
Assessment of Blood pressure (systolic and diastolic) helps determine the safety of the medications under study - ANF-RHO and Neulasta
Time Frame
~ 128 ± 2 days
Title
Clinically meaningful changes in vital signs during all chemotherapy cycles - Assessment of Heart rate
Description
Assessment of Heart rate helps determine the safety of the medications under study - ANF-RHO and Neulasta
Time Frame
~ 128 ± 2 days
Title
Clinically meaningful changes in vital signs during all chemotherapy cycles - Assessment of Respiratory rate
Description
Assessment of Respiratory rate helps determine the safety of the medications under study - ANF-RHO and Neulasta
Time Frame
~ 128 ± 2 days
Title
Clinically meaningful changes in vital signs during all chemotherapy cycles - Assessment of Body Temperature
Description
Assessment of Respiratory rate helps determine the safety of the medications under study - ANF-RHO and Neulasta
Time Frame
~ 128 ± 2 days
Title
Incidence of bone pain, determined by a numerical rating scale, as well as other reported adverse events
Time Frame
~ 128 ± 2 days
Title
Duration of bone pain, determined by a numerical rating scale, as well as other reported adverse events
Time Frame
~ 128 ± 2 days
Title
Severity of bone pain, determined by a numerical rating scale, as well as other reported adverse events
Time Frame
~ 128 ± 2 days
Title
Site of bone pain, determined by a numerical rating scale, as well as other reported adverse events
Time Frame
~ 128 ± 2 days
Title
Pharmacokinetic profile of ANF-RHO and Neulasta - Measurement of Maximum Plasma Concentration (Cmax)
Description
Cmax is the maximum concentration of the drug (either ANF-RHO or Neulasta) that is achieved after administration of a dose
Time Frame
~ 128 ± 2 days
Title
Pharmacokinetic profile of ANF-RHO and Neulasta - Measurement of Time taken to reach the maximum concentration (Tmax)
Description
Tmax is the time taken to reach the maximum concentration (Cmax) after administration of a dose.
Time Frame
~ 128 ± 2 days
Title
Pharmacokinetic profile of ANF-RHO and Neulasta - Measurement of half-life (T1/2)
Description
T1/2 is the time taken for ANF-RHO and Neulasta to reach half the value of their initial concentrations. T1/2 determination helps in understanding the duration for which ANF-RHO or Neulasta would be active upon administration.
Time Frame
~ 128 ± 2 days
Title
Pharmacokinetic profile of ANF-RHO and Neulasta - Area Under the Curve (AUC[0-t])
Description
AUC[0-t] is an important parameter for determining as to how much of the drug is available in the body after administration of a drug formulation, in this case ANF-RHO vs Neulasta. Understanding the AUC for both these drug formulations will help us to determine the efficacy and safety profiles of these medicines.
Time Frame
~ 128 ± 2 days
Title
Pharmacokinetic profile of ANF-RHO and Neulasta - Area Under the Curve (AUC[0-∞])
Description
Similar to AUC[0-t] which is estimated till time 't', in AUC[0-∞], the estimation is done on the concentration of the drug to an infinite time. Calculation of the AUC[0-∞], helps understand how much of the drug is available in the body at extremely low concentrations, beyond the limits of measurable concentrations.
Time Frame
~ 128 ± 2 days
Title
Pharmacokinetic profile of ANF-RHO and Neulasta - Area Under the Curve (AUC[0-t]/AUC[0-∞])
Description
The parameter AUC[0-t]/AUC[0-∞] is useful to calculate the fraction of the Total AUC that was added due to the extrapolated AUC (AUC[0-∞]). It helps understand if the methods employed for determining the total AUC and drug's availability in the body are correct.
Time Frame
~ 128 ± 2 days
Title
Incidence of anti-drug antibodies to ANF-RHO and Neulasta
Time Frame
~ 128 ± 2 days
10. Eligibility
Sex
Female
Gender Based
Yes
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Adult female patients, 18 years of age or older
Signed and dated written consent/assent by the patient or legally authorized representative
Histologically confirmed non-metastatic breast cancer
ECOG performance status ≤ 2
Myelosuppressive chemotherapy naive
Scheduled to receive and anticipated to complete the following chemotherapy regimen
FEC (fluorouracil/epirubicin (100) / cyclophosphamide) (3 cycles);
Docetaxel (3 cycles) chemotherapy
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)
Adequate cardiac function (e.g. LVEF > 50% as determined by standard care) and adequate hepatic function (e.g. liver transaminases < 2.5 x ULN)
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:
Known hypersensitivity to E.coli derived products or polyethylene glycol
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
Evidence of myelodysplasia, aplastic anemia, myelofibrosis, rheumatoid arthritis, systemic lupus erythematosus, or sickle cell disease
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
Previous exposure to filgrastim, perfilgrastim or lipegfilgrastim within 30 days before randomization
Treatment with systemically active antibiotics within 72 hours before chemotherapy
Chronic use of oral corticosteroids
Participation in a pharmacological clinical trial within 30 days before randomization
Clinical diagnosis of drug abuse or substance abuse within 30 days prior to screening
Documented alcohol abuse within 30 days prior to screening
Unwilling and/or not capable of ensuring compliance with the provisions of the study protocol
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
Other serious medical condition that would prevent individual from receiving protocol treatment
Facility Information:
Facility Name
Hôpital Saint Louis - Center des Maladies du Sein
City
Paris
ZIP/Postal Code
75475
Country
France
Facility Name
Institut de cancérologie Jean Godinot
City
Reims
ZIP/Postal Code
51100
Country
France
Facility Name
Strasbourg Oncologie Libérale
City
Strasbourg
ZIP/Postal Code
67000
Country
France
Facility Name
CHU de Tours
City
Tours
ZIP/Postal Code
37044
Country
France
Facility Name
Erasmus Medical Center
City
Rotterdam
ZIP/Postal Code
3008
Country
Netherlands
Facility Name
Ikazia Ziekenhuis
City
Rotterdam
ZIP/Postal Code
3038
Country
Netherlands
Facility Name
Maasstad Ziekenhuis
City
Rotterdam
ZIP/Postal Code
3079
Country
Netherlands
Facility Name
Franciscus Gasthuis & Vlietland
City
Schiedam
ZIP/Postal Code
3118
Country
Netherlands
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Randomized Phase 2, Dose-finding Efficacy, Safety Study of ANF-RHO™ Versus Neulasta® in Chemotherapy-Induced Neutropenia
We'll reach out to this number within 24 hrs