open-label, phase 1 study to evaluate duration of severe neutropenia after same-day dosing of eflapegrastim in patients with breast-cancer

Conditions: Neutropenia; Breast Cancer

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.

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.

Eligibility criteria:
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

Keywords: neutropenia early stage breast cancer long-acting myeloid growth factor docetaxel + cyclophosphamide (tc) chemotherapy