Breast Cancer, Neutropenia
Conditions
Keywords
Neutropenia, Early Stage Breast Cancer, Long-acting Myeloid Growth Factor, Docetaxel + Cyclophosphamide (TC) Chemotherapy
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.
Interventions
BIOLOGICALEflapegrastim
Administered in Cycle 1, 30 minutes after TC chemotherapy. Administered in Cycles 2-4, on day 2 of each cycle.
DRUGDocetaxel
75 mg/m\^2 IV infusion. Administered on Day 1 of each cycle.
DRUGCyclophosphamide
600 mg/m\^2 IV infusion. Administered on Day 1 of each cycle.
Sponsors
Spectrum Pharmaceuticals, Inc
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Considering two-phase study, where Expansion Phase followed Early Phase. The dosing within the Early Phase was in parallel assignment wherein participants were assigned to three arms in a 1:1:1 ratio. Patients completing Early Phase will enter the Expansion Phase to receive dosing in a single arm.
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients With Grade 4 Neutropenia in Cycle 1 | Cycle 1 is 21 days | — |
| 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 | — |
| 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. |
| 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: 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: 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) | — |
| 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) | — |
Countries
United States
Outcome results
None listed