Open-Label, Phase 1 Study to Evaluate Duration of Severe Neutropenia After Same-Day Dosing of Eflapegrastim in Patients With Breast-Cancer

Overview

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.

Full Title of Study: “Open-Label, Phase 1 Study to Evaluate Duration of Severe Neutropenia After the Same-Day, Varying Dosing Time Schedules of Eflapegrastim Administration in Patients With Breast-Cancer Receiving Docetaxel and Cyclophosphamide”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Sequential Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: July 31, 2024

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

  • Biological: Eflapegrastim
    • Administered in Cycle 1, 30 minutes after TC chemotherapy. Administered in Cycles 2-4, on day 2 of each cycle.
  • Biological: Eflapegrastim
    • Administered in Cycle 1, 3 hours after TC chemotherapy. Administered in Cycles 2-4, on day 2 of each cycle.
  • Biological: Eflapegrastim
    • Administered in Cycle 1, 5 hours after TC chemotherapy. Administered in Cycles 2-4, on day 2 of each cycle.
  • Biological: Eflapegrastim
    • Administered in Cycles 1-4, 30 mins after TC chemotherapy.
  • Drug: Docetaxel
    • 75 mg/m^2 IV infusion. Administered on Day 1 of each cycle.
  • Drug: Cyclophosphamide
    • 600 mg/m^2 IV infusion. Administered on Day 1 of each cycle.

Arms, Groups and Cohorts

  • Experimental: Early Phase: Eflapegrastim @ 30mins post TC
    • 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.
  • Experimental: Early Phase: Eflapegrastim @ 3 hours post TC
    • 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.
  • Experimental: Early Phase: Eflapegrastim @ 5 hours post TC
    • 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.
  • Experimental: Expansion Phase: Eflapegrastim @ 30 mins post TC
    • 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.

Clinical Trial Outcome Measures

Primary Measures

  • Time to Recovery of Absolute Neutrophil Count (ANC) From Nadir to ≥1.5×10^9/L in Cycle 1
    • Time Frame: 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 Measures

  • Duration of Grade 4 Neutropenia (DSN) in Cycle 1
    • Time Frame: Cycle 1 is 21 days
    • DSN is defined as the number of days of severe neutropenia where the ANC<0.5×10^9/L from the first occurrence of an ANC below the threshold.
  • Proportion of Patients With Grade 4 Neutropenia in Cycle 1
    • Time Frame: Cycle 1 is 21 days
  • Incidence of Grade 3 Febrile Neutropenia (FN) in Cycle 1
    • Time Frame: Cycle 1 is 21 days
    • FN is defined as having an ANC<1.0×10^9/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
    • Time Frame: Cycle 1 is 21 days
  • Expansion Phase: Time to Recovery of ANC From Nadir to ≥1.5×10^9/L in Cycles 2-4
    • Time Frame: 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
    • Time Frame: 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 <0.5×10^9/L from the first occurrence of an ANC below the threshold.
  • Expansion Phase: Proportion of Patients With Grade 4 Neutropenia in Cycles 2-4
    • Time Frame: Cycles 2-4 (cycle length=21 days) (up to approximately 63 days)
  • Expansion Phase: Incidence of FN in Cycles 2-4
    • Time Frame: Cycles 2-4 (cycle length=21 days) (up to approximately 63 days)
    • FN is defined as having an ANC<1.0×10^9/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
    • Time Frame: 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
    • Time Frame: 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
    • Time Frame: Up to approximately 40 days after the last dose of study treatment or early study discontinuation (up to approximately 4 months)

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 55 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Spectrum Pharmaceuticals, Inc
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Contact(s)
    • Howard Franklin, MD, 224.419.7106, Hfranklin@assertiotx.com

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