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

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04187898
• Other study ID #: SPI-GCF-104
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: March 11, 2020
• Est. completion date: July 31, 2024

Study information

• Verified date: May 2024
• Source: Spectrum Pharmaceuticals, Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 50
• Est. completion date: July 31, 2024
• Est. primary completion date: July 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Neutropenia

Intervention

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

Locations

Country	Name	City	State
United States	Pacific Cancer Medical Center	Anaheim	California
United States	SCL Health Research Institute, Inc.	Billings	Montana
United States	City of Hope	Long Beach	California
United States	BRCR Medical Center, Inc.	Plantation	Florida
United States	ACRC/ Arizona Clinical Research Center	Tucson	Arizona
United States	Bond & Steele Clinic, P.A.	Winter Haven	Florida
United States	Mercy Health Youngstown	Youngstown	Ohio
United States	Yuma Regional Medical Center Cancer Center	Yuma	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Spectrum Pharmaceuticals, Inc

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Proportion of Patients With Grade 4 Neutropenia in Cycle 1		Cycle 1 is 21 days
Secondary	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
Secondary	Incidence of Neutropenic Complications, Including Hospitalization due to Neutropenia, FN, and use of Anti-infectives During Cycle 1		Cycle 1 is 21 days
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)