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

Primary Purpose

Neutropenia, Breast Cancer

Status

Recruiting

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Eflapegrastim

Docetaxel

Cyclophosphamide

About this trial

This is an interventional treatment trial for Neutropenia focused on measuring Neutropenia, Early Stage Breast Cancer, Long-acting Myeloid Growth Factor, Docetaxel + Cyclophosphamide (TC) Chemotherapy

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesDoes not accept healthy volunteers

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

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Arm Label

Early Phase: Eflapegrastim @ 30mins post TC

Early Phase: Eflapegrastim @ 3 hours post TC

Early Phase: Eflapegrastim @ 5 hours post TC

Expansion Phase: Eflapegrastim @ 30 mins post TC

Arm Description

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

Proportion of Patients With Grade 4 Neutropenia in Cycle 1

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).

Incidence of Neutropenic Complications, Including Hospitalization due to Neutropenia, FN, and use of Anti-infectives During Cycle 1

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.

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.

Expansion Phase: Proportion of Patients With Grade 4 Neutropenia in Cycles 2-4

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).

Expansion Phase: Incidence of Neutropenic Complications, Including Hospitalization due to Neutropenia, FN, and use of Anti-infectives During Cycles 2-4

Number of Patients With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) as a Measure of Safety

Proportion of Patients Discontinuing Because of a TEAE

Full Information

NCT ID

NCT04187898

First Posted

October 30, 2019

Last Updated

November 4, 2022

Sponsor

Spectrum Pharmaceuticals, Inc

1. Study Identification

Unique Protocol Identification Number

NCT04187898

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

November 2022

Overall Recruitment Status

Recruiting

Study Start Date

March 11, 2020 (Actual)

Primary Completion Date

December 31, 2024 (Anticipated)

Study Completion Date

June 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Spectrum Pharmaceuticals, Inc

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

Brief 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.

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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Neutropenia, Breast Cancer

Keywords

Neutropenia, Early Stage Breast Cancer, Long-acting Myeloid Growth Factor, Docetaxel + Cyclophosphamide (TC) Chemotherapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

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)

Allocation

Randomized

Enrollment

90 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Early Phase: Eflapegrastim @ 30mins post TC

Arm Type

Experimental

Arm Description

Arm Title

Early Phase: Eflapegrastim @ 3 hours post TC

Arm Type

Experimental

Arm Description

Arm Title

Early Phase: Eflapegrastim @ 5 hours post TC

Arm Type

Experimental

Arm Description

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.

Arm Title

Expansion Phase: Eflapegrastim @ 30 mins post TC

Arm Type

Experimental

Arm Description

Intervention Type

Biological

Intervention Name(s)

Eflapegrastim

Intervention Description

Administered in Cycle 1, 30 minutes after TC chemotherapy. Administered in Cycles 2-4, on day 2 of each cycle.

Intervention Type

Biological

Intervention Name(s)

Eflapegrastim

Intervention Description

Administered in Cycle 1, 3 hours after TC chemotherapy. Administered in Cycles 2-4, on day 2 of each cycle.

Intervention Type

Biological

Intervention Name(s)

Eflapegrastim

Intervention Description

Administered in Cycle 1, 5 hours after TC chemotherapy. Administered in Cycles 2-4, on day 2 of each cycle.

Intervention Type

Biological

Intervention Name(s)

Eflapegrastim

Intervention Description

Administered in Cycles 1-4, 30 mins after TC chemotherapy.

Intervention Type

Drug

Intervention Name(s)

Docetaxel

Other Intervention Name(s)

Taxotere

Intervention Description

75 mg/m^2 IV infusion. Administered on Day 1 of each cycle.

Intervention Type

Drug

Intervention Name(s)

Cyclophosphamide

Other Intervention Name(s)

Cytoxan

Intervention Description

600 mg/m^2 IV infusion. Administered on Day 1 of each cycle.

Primary Outcome Measure Information:

Title

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

Description

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.

Time Frame

Cycle 1 is 21 days

Secondary Outcome Measure Information:

Title

Duration of Grade 4 Neutropenia (DSN) in Cycle 1

Description

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.

Time Frame

Cycle 1 is 21 days

Title

Proportion of Patients With Grade 4 Neutropenia in Cycle 1

Time Frame

Cycle 1 is 21 days

Title

Incidence of Grade 3 Febrile Neutropenia (FN) in Cycle 1

Description

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).

Time Frame

Cycle 1 is 21 days

Title

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

Title

Expansion Phase: Time to Recovery of ANC From Nadir to ≥1.5×10^9/L in Cycles 2-4

Description

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.

Time Frame