A Phase III, Randomized, Multi-Centre, Open-Label, Fixed Dose, Neulasta® Active-Controlled Clinical Trial of F-627 in Women With Breast Cancer Receiving Myelotoxic Chemotherapy
Overview
- Phase
- Phase 3
- Intervention
- Neulasta
- Conditions
- Breast Cancer
- Sponsor
- EVIVE Biotechnology
- Enrollment
- 393
- Locations
- 1
- Primary Endpoint
- Duration in Days of Grade 4 Neutropenia in Chemotherapy Cycle 1
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
This is a randomized, multi-center, single dose, open-label and Neulasta controlled phase 3 study to evaluate the efficacy and safety of F-627 in women with Stage I - III invasive breast cancer receiving chemotherapy treatment.
Detailed Description
This is a Phase III, global, two arm, open label clinical study will randomize approximately 400 female subjects (approximately 200 per arm) with Stage I - III invasive breast cancer who are to receive neoadjuvant or adjuvant myelotoxic TC chemotherapy treatment (docetaxel + cyclophosphamide, 75 and 600 mg/m2, respectively). Subjects in this study will be those who are scheduled to undergo at least four 21-day cycles of chemotherapy treatment. Subjects may be scheduled for more than 4 cycles of chemotherapy; however, study participation will be limited to a subject's first 4 cycles. The primary objective of this study will be to evaluate the efficacy of F-627 given as a single fixed dose (20 mg) pre-filled syringe as compared to Neulasta® standard dosing (6 mg) in the first chemotherapy cycle. The primary endpoint will be the duration of grade 4 (severe) neutropenia - the number of days in which the patient has had an absolute neutrophil count (ANC \<0.5 x 10\^9/L) observed in chemotherapy cycle 1. Approximately 24 hours after chemotherapy completion in each cycle (Day 2 of the cycle), subjects will receive one of the following treatments: Arm 1: F-627, 20 mg fixed dose pre-filled syringe, administered on Day 2 of each of 4 chemotherapy cycles. Arm 2: 6 mg fixed dose Neulasta®, administered on Day 2 of each of 4 chemotherapy cycles Randomization will occur in an equal ratio (1:1) using a central randomization system (IWRS) on Day 1 of the study, the day of chemotherapy administration for the first chemotherapy cycle. This study is open-label, however, study drug injections are to be administered separately by qualified study personnel to allow study investigators to remain blinded and perform study assessments without knowledge of treatment assignment.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Show evidence of a personally signed and dated informed consent document indicating that the patient has been informed of all pertinent aspects of the trial.
- •Females ≥18 years of age.
- •Diagnosed with Stage I-III breast cancer.
- •Subject is scheduled to undergo 4 cycles of neoadjuvant or adjuvant TC chemotherapy (docetaxel, cyclophosphamide, 75, 600 mg/m2, respectively).
- •ECOG Performance status of ≤
- •WBC count ≥4.0 × 109/L, hemoglobin ≥11.5 g/dL and a platelet count ≥150 × 109/L.
- •Demonstrate adequate renal, hepatic, and cardiac function (liver function tests \[alanine aminotransferase {ALT}, aspartate aminotransferase {AST}, alkaline phosphatase, and total bilirubin\]) should be less than 2.5x the upper limits of normal (ULN). Serum creatinine should be less than 1.7x ULN.
- •All subjects must agree to use at least one of the following types of contraception: intrauterine device, implantable progesterone device, progesterone intramuscular injection, or oral contraceptive, which has been started at least one month prior to visit one and will continue for the duration of the trial. The contraceptive patch or condom use with spermicide is also acceptable forms of contraception as long as they will be used continually throughout the duration of the trial.
Exclusion Criteria
- •Subject is \<18 years of age.
- •Disease progression has occurred while receiving a taxane regimen.
- •Subject has undergone radiation therapy within 4 weeks of enrollment.
- •Subject has undergone bone marrow or stem-cell transplantation.
- •Subject has a history of prior malignancy other than breast cancer that is NOT in remission.
- •Subjects that have used G-CSF or any other drug that may potentiate the release of neutrophils (i.e., lithium) within 6 weeks of the screening period are excluded.
- •Subject has had chemotherapy within 180 days of screening.
- •Subject has documented congestive heart failure, cardiomyopathy or myocardial infarction by clinical diagnosis, electrocardiogram (ECG) test, or any other relevant test.
- •History of alcohol or drug abuse that would interfere with the ability to be compliant with the study procedure.
- •Unwillingness to participate in the study.
Arms & Interventions
Neulasta
6 mg fixed dose Neulasta®, administered on Day 2 of each of 4 chemotherapy cycles
Intervention: Neulasta
F-627
F-627, 20 mg fixed dose pre-filled syringe, administered on Day 2 of each of 4 chemotherapy cycles.
Intervention: F-627
Outcomes
Primary Outcomes
Duration in Days of Grade 4 Neutropenia in Chemotherapy Cycle 1
Time Frame: The first of 4, 21-day chemotherapy cycles (average 3 weeks)
Eligible subjects were randomized in a 1:1 ratio. Subjects were dosed with either the F 627 20 mg/dose PFS or Neulasta® 6 mg/dose as the study drug in each chemotherapy cycle. Subjects remained in their assigned treatment arm throughout the study. Subjects were dosed subcutaneously (SC) 24 to 28 hours after receiving TC chemotherapy (75 mg/m2 docetaxel + 600 mg/m2 cyclophosphamide) on Day 2 of each chemotherapy cycle that the subject underwent (up to 4 cycles). Grade 4 (severe) neutropenia was defined as ANC \<0.5 × 109/L within the first 12 days of chemotherapy.
Secondary Outcomes
- The Number of Participants With Febrile Neutropenia Considering All Chemotherapy Cycles.(across all 4 chemotherapy cycles (average 84 days))
- The Number of Participants With Grade 4 Neutropenia for Chemotherapy Cycle 1(The first of 4, 21-day chemotherapy cycles (average 3 weeks))
- Duration in Days of Use of Intravenous Antibiotic(across all 4 chemotherapy cycles (average 84 days))
- Duration in Days of Hospitalization(across all 4 chemotherapy cycles (average 84 days))
- The Number of Participants in Hospitalization for Febrile Neutropenia or Any Infection Considering All Chemotherapy Cycles(across all 4 chemotherapy cycles (average 84 days))
- The Number of Participants With Use of IV Antibiotics Considering All Chemotherapy Cycles.(across all 4 chemotherapy cycles (average 84 days))