Open-Label, Phase 1 Study to Evaluate Duration of Severe Neutropenia After Same-Day Dosing of Eflapegrastim in Patients With Breast-Cancer
- Conditions
- NeutropeniaBreast Cancer
- Interventions
- Registration Number
- NCT04187898
- Lead Sponsor
- Spectrum Pharmaceuticals, Inc
- Brief Summary
The purpose of this study is to compare the effect of Eflapegrastim on duration of neutropenia in patients with early-stage breast cancer when administered at varying intervals following Docetaxel and Cyclophosphamide administration.
- Detailed Description
This is a Phase 1, randomized, open label, actively-controlled study to evaluate the same day dosing of Eflapegrastim on duration of neutropenia when administered at varying intervals following Docetaxel and Cyclophosphamide (TC) chemotherapy in patients with early-stage breast cancer.
The study will be conducted in two phases: Early Phase and Expansion Phase.
1. In the Early Phase, approximately 45 patients were enrolled and randomized in a 1:1:1 ratio to 3 dosing time schedule arms. Each cycle was of 21 days. Total 4 cycles were evaluated for this phase. On Day 1 of Cycle 1, patients received Docetaxel and Cyclophosphamide (TC) chemotherapy followed by administration of Eflapegrastim at 1 of 3-time schedules post-TC (30 minutes \[mins\], 3 hours or 5 hours). During Cycles 2-4, patients received Eflapegrastim 24 hours after TC administration (on Day 2).
2. In the Expansion Phase, additional 45 patients will be enrolled in Cycles 1-4, who will receive fixed dose of Eflapegrastim 30 mins after TC administration (on Day 1).
Safety evaluations will be conducted once the first 3 patients (for Early Phase) and the first 6 patients (for Expansion Phase) have completed Cycle 1 to determine if it is safe for patients to continue in that particular treatment arm.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 50
- Willing and capable of giving written Informed Consent and able to adhere to study drug dosing time and blood draw schedules
- New diagnosis of histologically confirmed early-stage breast cancer (ESBC), defined as operable Stage I to Stage IIIA breast cancer
- Candidate to receive adjuvant or neoadjuvant TC chemotherapy
- Age must be at least 18 years for the Early Phase, and between 18 to ≤55 years for the Expansion Phase
- ANC ≥1.5×10^9/liter (L).
- Platelet count ≥100×10^9/liter (L).
- Hemoglobin >10 grams per deciliter (g/dL).
- Calculated creatinine clearance >50 milliliter per minute (mL/min).
- Total bilirubin ≤1.5 milligrams per deciliter (mg/dL).
- Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) ≤2.5×upper limit of normal (ULN).
- Alkaline phosphatase ≤2.0×ULN.
- Eastern Cooperative Oncology Group (ECOG) ≤2
- Willing to practice 2 forms of contraceptives (1 must be a barrier method), from study entry through 30 days after last dose of study drug/ early discontinuation
- Negative urine pregnancy test within 30 days before randomization
- Active concurrent malignancy (except non melanoma skin cancer or carcinoma in situ of the cervix) or life-threatening disease
- Known sensitivity to Escherichia coli (E. coli) derived products
- Concurrent adjuvant cancer therapy other than the trial-specified therapies
- Locally recurrent/metastatic breast cancer
- Previous exposure to filgrastim, pegfilgrastim, or other G-CSF products in clinical development within 3 months prior to the administration of study drug
- Receiving anti-infectives, has an underlying medical condition or other serious illness that would impair the ability to receive protocol-specified treatment
- Used any investigational drugs, biologics, or devices within 30 days prior to study treatment or plans to use any of these during the course of the study
- Prior bone marrow or stem cell transplant
- Prior radiation therapy within 30 days prior to enrollment
- Major surgery within 30 days prior to enrollment
- Pregnant or breastfeeding
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Early Phase: Eflapegrastim @ 30mins post TC Eflapegrastim Eflapegrastim (13.2 mg/0.6 mL fixed dose, equivalent to 3.6 mg granulocyte colony-stimulating factor \[G-CSF\]). Supplied in prefilled single-use syringes for subcutaneous injection. Cycle 1: Administered on the same day as TC chemotherapy, 30 minutes from the end of TC administration. Cycles 2-4: Administered 24 hours after TC chemotherapy administration. Each cycle is 21 days. Early Phase: Eflapegrastim @ 30mins post TC Docetaxel Eflapegrastim (13.2 mg/0.6 mL fixed dose, equivalent to 3.6 mg granulocyte colony-stimulating factor \[G-CSF\]). Supplied in prefilled single-use syringes for subcutaneous injection. Cycle 1: Administered on the same day as TC chemotherapy, 30 minutes from the end of TC administration. Cycles 2-4: Administered 24 hours after TC chemotherapy administration. Each cycle is 21 days. Early Phase: Eflapegrastim @ 3 hours post TC Eflapegrastim Eflapegrastim (13.2 mg/0.6 mL fixed dose, equivalent to 3.6 mg G-CSF). Supplied in prefilled single-use syringes for subcutaneous injection. Cycle 1: Administered on the same day as TC chemotherapy, 3 hours from the end of TC administration. Cycles 2-4: Administered 24 hours after TC chemotherapy administration. Each cycle is 21 days. Early Phase: Eflapegrastim @ 30mins post TC Cyclophosphamide Eflapegrastim (13.2 mg/0.6 mL fixed dose, equivalent to 3.6 mg granulocyte colony-stimulating factor \[G-CSF\]). Supplied in prefilled single-use syringes for subcutaneous injection. Cycle 1: Administered on the same day as TC chemotherapy, 30 minutes from the end of TC administration. Cycles 2-4: Administered 24 hours after TC chemotherapy administration. Each cycle is 21 days. Early Phase: Eflapegrastim @ 3 hours post TC Docetaxel Eflapegrastim (13.2 mg/0.6 mL fixed dose, equivalent to 3.6 mg G-CSF). Supplied in prefilled single-use syringes for subcutaneous injection. Cycle 1: Administered on the same day as TC chemotherapy, 3 hours from the end of TC administration. Cycles 2-4: Administered 24 hours after TC chemotherapy administration. Each cycle is 21 days. Early Phase: Eflapegrastim @ 3 hours post TC Cyclophosphamide Eflapegrastim (13.2 mg/0.6 mL fixed dose, equivalent to 3.6 mg G-CSF). Supplied in prefilled single-use syringes for subcutaneous injection. Cycle 1: Administered on the same day as TC chemotherapy, 3 hours from the end of TC administration. Cycles 2-4: Administered 24 hours after TC chemotherapy administration. Each cycle is 21 days. Early Phase: Eflapegrastim @ 5 hours post TC Docetaxel Eflapegrastim (13.2 mg/0.6 mL fixed dose, equivalent to 3.6 mg G-CSF). Supplied in prefilled single-use syringes for subcutaneous injection. Cycle 1: Administered on the same day as TC chemotherapy, 5 hours from the end of TC administration. Cycles 2-4: Administered 24 hours after TC chemotherapy administration. Each cycle is 21 days. Expansion Phase: Eflapegrastim @ 30 mins post TC Eflapegrastim Eflapegrastim (13.2 mg/0.6 mL fixed dose, equivalent to 3.6 mg G-CSF). Supplied in prefilled single-use syringes for subcutaneous injection. Cycles 1-4: Administered on the same day as TC chemotherapy, 30 minutes following the end of TC administration. Each cycle is 21 days. Early Phase: Eflapegrastim @ 5 hours post TC Cyclophosphamide Eflapegrastim (13.2 mg/0.6 mL fixed dose, equivalent to 3.6 mg G-CSF). Supplied in prefilled single-use syringes for subcutaneous injection. Cycle 1: Administered on the same day as TC chemotherapy, 5 hours from the end of TC administration. Cycles 2-4: Administered 24 hours after TC chemotherapy administration. Each cycle is 21 days. Expansion Phase: Eflapegrastim @ 30 mins post TC Docetaxel Eflapegrastim (13.2 mg/0.6 mL fixed dose, equivalent to 3.6 mg G-CSF). Supplied in prefilled single-use syringes for subcutaneous injection. Cycles 1-4: Administered on the same day as TC chemotherapy, 30 minutes following the end of TC administration. Each cycle is 21 days. Expansion Phase: Eflapegrastim @ 30 mins post TC Cyclophosphamide Eflapegrastim (13.2 mg/0.6 mL fixed dose, equivalent to 3.6 mg G-CSF). Supplied in prefilled single-use syringes for subcutaneous injection. Cycles 1-4: Administered on the same day as TC chemotherapy, 30 minutes following the end of TC administration. Each cycle is 21 days. Early Phase: Eflapegrastim @ 5 hours post TC Eflapegrastim Eflapegrastim (13.2 mg/0.6 mL fixed dose, equivalent to 3.6 mg G-CSF). Supplied in prefilled single-use syringes for subcutaneous injection. Cycle 1: Administered on the same day as TC chemotherapy, 5 hours from the end of TC administration. Cycles 2-4: Administered 24 hours after TC chemotherapy administration. Each cycle is 21 days.
- Primary Outcome Measures
Name Time Method Time to Recovery of Absolute Neutrophil Count (ANC) From Nadir to ≥1.5×10^9/L in Cycle 1 Cycle 1 is 21 days Time to ANC Recovery is defined as the time from chemotherapy administration until the patient's ANC increases to ≥1.5×10\^9/liter (L) after the expected nadir.
- Secondary Outcome Measures
Name Time Method Duration of Grade 4 Neutropenia (DSN) in Cycle 1 Cycle 1 is 21 days DSN is defined as the number of days of severe neutropenia where the ANC\<0.5x10\^9/L from the first occurrence of an ANC below the threshold.
Expansion Phase: Time to Recovery of ANC From Nadir to ≥1.5×10^9/L in Cycles 2-4 Cycles 2-4 (cycle length=21 days) (up to approximately 63 days) Time to ANC Recovery is defined as the time from chemotherapy administration until the patient's ANC increases to ≥1.5×10\^9/L after the expected nadir.
Expansion Phase: DSN in Cycles 2-4 Cycles 2-4 (cycle length=21 days) (up to approximately 63 days) DSN is defined as the number of days of severe neutropenia where the ANC \<0.5x10\^9/L from the first occurrence of an ANC below the threshold.
Expansion Phase: Incidence of FN in Cycles 2-4 Cycles 2-4 (cycle length=21 days) (up to approximately 63 days) FN is defined as having an ANC\<1.0x10\^9/L and either a single temperature of \>38.3 degrees Celsius (101.0 F) or a sustained temperature of \>38.0 degrees Celsius (100.4 F).
Expansion Phase: Proportion of Patients With Grade 4 Neutropenia in Cycles 2-4 Cycles 2-4 (cycle length=21 days) (up to approximately 63 days) Expansion Phase: Incidence of Neutropenic Complications, Including Hospitalization due to Neutropenia, FN, and use of Anti-infectives During Cycles 2-4 Cycles 2-4 (cycle length=21 days) (up to approximately 63 days) Number of Patients With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) as a Measure of Safety Up to approximately 40 days after the last dose of study treatment or early study discontinuation (up to approximately 4 months) Proportion of Patients Discontinuing Because of a TEAE Up to approximately 40 days after the last dose of study treatment or early study discontinuation (up to approximately 4 months) Incidence of Grade 3 Febrile Neutropenia (FN) in Cycle 1 Cycle 1 is 21 days FN is defined as having an ANC\<1.0x10\^9/L and either a single temperature of \>38.3 degrees Celsius (101.0 Fahrenheit \[F\]) or a sustained temperature of \>38.0 degrees Celsius (100.4 F).
Incidence of Neutropenic Complications, Including Hospitalization due to Neutropenia, FN, and use of Anti-infectives During Cycle 1 Cycle 1 is 21 days Proportion of Patients With Grade 4 Neutropenia in Cycle 1 Cycle 1 is 21 days
Trial Locations
- Locations (8)
BRCR Medical Center, Inc.
🇺🇸Plantation, Florida, United States
City of Hope
🇺🇸Long Beach, California, United States
Mercy Health Youngstown
🇺🇸Youngstown, Ohio, United States
ACRC/ Arizona Clinical Research Center
🇺🇸Tucson, Arizona, United States
Yuma Regional Medical Center Cancer Center
🇺🇸Yuma, Arizona, United States
Pacific Cancer Medical Center
🇺🇸Anaheim, California, United States
SCL Health Research Institute, Inc.
🇺🇸Billings, Montana, United States
Bond & Steele Clinic, P.A.
🇺🇸Winter Haven, Florida, United States