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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Breast Cancer; Neutropenia
• Intervention / Treatment: Biological: Eflapegrastim; Biological: Eflapegrastim; Biological: Eflapegrastim; Biological: Eflapegrastim; Drug: Docetaxel; Drug: Cyclophosphamide

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.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85715
      • ACRC/ Arizona Clinical Research Center
    • Yuma, Arizona, United States, 85364
      • Yuma Regional Medical Center Cancer Center
  • California
    • Anaheim, California, United States, 92801
      • Pacific Cancer Medical Center
    • Long Beach, California, United States, 90813
      • City of Hope
  • Florida
    • Plantation, Florida, United States, 33322
      • BRCR Medical Center, Inc.
    • Winter Haven, Florida, United States, 33881
      • Bond & Steele Clinic, P.A.
  • Montana
    • Billings, Montana, United States, 59102
      • SCL Health Research Institute, Inc.
  • Ohio
    • Youngstown, Ohio, United States, 44501
      • Mercy Health Youngstown

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	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.; Other Names: Taxotere; Drug: Cyclophosphamide; 600 mg/m^2 IV infusion. Administered on Day 1 of each cycle.; Other Names: Cytoxan
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.	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.; Other Names: Taxotere; Drug: Cyclophosphamide; 600 mg/m^2 IV infusion. Administered on Day 1 of each cycle.; Other Names: Cytoxan
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.	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.; Other Names: Taxotere; Drug: Cyclophosphamide; 600 mg/m^2 IV infusion. Administered on Day 1 of each cycle.; Other Names: Cytoxan
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.	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.; Other Names: Taxotere; Drug: Cyclophosphamide; 600 mg/m^2 IV infusion. Administered on Day 1 of each cycle.; Other Names: Cytoxan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Recovery of Absolute Neutrophil Count (ANC) From Nadir to ≥1.5×10^9/L in Cycle 1	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.	Cycle 1 is 21 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Grade 4 Neutropenia (DSN) in Cycle 1	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.	Cycle 1 is 21 days
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	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).	Cycle 1 is 21 days
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	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.	Cycles 2-4 (cycle length=21 days) (up to approximately 63 days)
Expansion Phase: DSN in Cycles 2-4	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.	Cycles 2-4 (cycle length=21 days) (up to approximately 63 days)
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 FN in Cycles 2-4	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).	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)

Collaborators and Investigators

• Sponsor: Spectrum Pharmaceuticals, Inc
• Investigators: Study Director: Shanta Chawla, MD, Spectrum Pharmaceuticals, Inc

Study record dates

Study Major Dates

• Study Start (Actual): March 11, 2020
• Primary Completion (Estimated): July 31, 2024
• Study Completion (Estimated): July 31, 2024

Study Registration Dates

• First Submitted: October 30, 2019
• First Submitted That Met QC Criteria: December 3, 2019
• First Posted (Actual): December 5, 2019

Study Record Updates

• Last Update Posted (Actual): July 11, 2024
• Last Update Submitted That Met QC Criteria: July 10, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Early Stage Breast Cancer; Neutropenia; Long-acting Myeloid Growth Factor; Docetaxel + Cyclophosphamide (TC) Chemotherapy
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Hematologic Diseases; Breast Diseases; Agranulocytosis; Leukopenia; Leukocyte Disorders; Cytopenia; Breast Neoplasms; Neutropenia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Docetaxel; Cyclophosphamide
• Other Study ID Numbers: SPI-GCF-104

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No