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

Study Overview
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Brief Summary
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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
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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. 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). 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.

Official Title
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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

Conditions
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Neutropenia, Breast Cancer

Intervention / Treatment
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* Biological: Eflapegrastim
* Biological: Eflapegrastim
* Biological: Eflapegrastim
* Biological: Eflapegrastim
* Drug: Docetaxel
* Drug: Cyclophosphamide


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Early Phase: Eflapegrastim @ 30mins post TC<br>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<br>* Administered in Cycle 1, 30 minutes after TC chemotherapy. Administered in Cycles 2-4, on day 2 of each cycle.<br>Drug: Docetaxel<br>* 75 mg/m^2 IV infusion. Administered on Day 1 of each cycle.<br>* Other names: Taxotere;Drug: Cyclophosphamide<br>* 600 mg/m^2 IV infusion. Administered on Day 1 of each cycle.<br>* Other names: Cytoxan;|
| Experimental: Early Phase: Eflapegrastim @ 3 hours post TC<br>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<br>* Administered in Cycle 1, 3 hours after TC chemotherapy. Administered in Cycles 2-4, on day 2 of each cycle.<br>Drug: Docetaxel<br>* 75 mg/m^2 IV infusion. Administered on Day 1 of each cycle.<br>* Other names: Taxotere;Drug: Cyclophosphamide<br>* 600 mg/m^2 IV infusion. Administered on Day 1 of each cycle.<br>* Other names: Cytoxan;|
| Experimental: Early Phase: Eflapegrastim @ 5 hours post TC<br>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<br>* Administered in Cycle 1, 5 hours after TC chemotherapy. Administered in Cycles 2-4, on day 2 of each cycle.<br>Drug: Docetaxel<br>* 75 mg/m^2 IV infusion. Administered on Day 1 of each cycle.<br>* Other names: Taxotere;Drug: Cyclophosphamide<br>* 600 mg/m^2 IV infusion. Administered on Day 1 of each cycle.<br>* Other names: Cytoxan;|
| Experimental: Expansion Phase: Eflapegrastim @ 30 mins post TC<br>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<br>* Administered in Cycles 1-4, 30 mins after TC chemotherapy.<br>Drug: Docetaxel<br>* 75 mg/m^2 IV infusion. Administered on Day 1 of each cycle.<br>* Other names: Taxotere;Drug: Cyclophosphamide<br>* 600 mg/m^2 IV infusion. Administered on Day 1 of each cycle.<br>* Other names: Cytoxan;|

What is the study measuring?
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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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neutropenia, Early Stage Breast Cancer, Long-acting Myeloid Growth Factor, Docetaxel + Cyclophosphamide (TC) Chemotherapy