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

Sponsor

Spectrum Pharmaceuticals, Inc (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04187898

Collaborator

(none)

Enrollment

Locations

Arms

21.7

Anticipated Duration (Months)

6.4

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Neutropenia Breast Cancer	Drug: Eflapegrastim Drug: Eflapegrastim Drug: Eflapegrastim Drug: Docetaxel Drug: Cyclophosphamide	Phase 1

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 .

Approximately 45 patients will be enrolled and randomized in a 1:1:1 ratio to 3 dosing time schedule arms.

Each cycle will be 21 days. Total 4 cycles will be evaluated for this study. On Day 1 of Cycle 1, patients will receive Docetaxel and Cyclophosphamide (TC)chemotherapy followed by administration of Eflapegrastim at 1 of 3 time schedules post-TC (30mins, 3 hours or 5 hours). During Cycles 2-4, patients will receive Eflapegrastim 24 hours after TC administration (on Day 2).

Safety evaluations will be conducted once the first 3 patients in each arm have completed Cycle 1 to determine if it is safe for patients to continue in that particular treatment arm.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

45 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Participant)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Mar 11, 2020

Anticipated Primary Completion Date :

May 31, 2021

Anticipated Study Completion Date :

Jan 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Eflapegrastim @ 30mins 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, 30 minutes from the end of TC administration. Cycles 2-4: Administered 24 hours after TC chemotherapy administration.	Drug: Eflapegrastim Administered in Cycle 1, 30 minutes after TC chemotherapy. Administered in Cycle 2-4, on day 2 of each cycle. 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: 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.	Drug: Eflapegrastim Administered in Cycle 1, 3 hours after TC chemotherapy. Administered in Cycle 2-4, on day 2 of each cycle. 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: 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.	Drug: Eflapegrastim Administered in Cycle 1, 5 hours after TC chemotherapy. Administered in Cycle 2-4, on day 2 of each cycle. 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

Arm

Intervention/Treatment

Experimental: Eflapegrastim @ 30mins 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, 30 minutes from the end of TC administration. Cycles 2-4: Administered 24 hours after TC chemotherapy administration.

Drug: Eflapegrastim

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

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: 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.

Drug: Eflapegrastim

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

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: 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.

Drug: Eflapegrastim

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

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

Outcome Measures

Primary Outcome Measures

Duration of Grade 4 Neutropenia (DSN) in Cycle 1 [Cycle 1 is 21 days]
DSN is defined as the number of days of severe neutropenia where the Absolute Neutrophil Count (ANC<0.5x10^9/L) from the first occurrence of an ANC below the threshold.

Secondary Outcome Measures

Neutropenia in Cycle 1. [Cycle 1 is 21 days]
Time to recovery of severe neutropenia in Cycle 1. [Cycle 1 is 21 days]
Incidence of grade 3 febrile neutropenia (FN) in Cycle 1 [Cycle 1 is 21 days]
FN is defined as having an ANC<1.0x10^9/L and either a single temperature of >38.3 degrees celcius (101.0 F) or a sustained temperature of >38.0 degrees celcius (100.4 F).
Pharmacokinetics (PK) of Eflapegrastim in Cycle 1 [Cycle 1 is 21 days]
Will be measured by the concentration of Eflapegrastim in plasma at various timepoints in Cycle 1.
Incidence of neutropenic complications, including hospitalization due to neutropenia, febrile neutropenia, and use of anti-infectives during Cycle 1 [Cycle 1 is 21 days]
Number of patients with adverse events/serious adverse events as a measure of safety [5 months]

Other Outcome Measures

CD34+ count in the peripheral blood during Cycle 1 [First 10 days of Cycle 1]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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
ANC ≥1.5×10^9/L
Platelet count ≥100×10^9/L.
Hemoglobin >10 g/dL.
Calculated creatinine clearance > 50 mL/min.
Total bilirubin ≤1.5 mg/dL.
AST/SGOT and ALT/SGPT ≤2.5×ULN. (upper limit of normal)
Alkaline phosphatase ≤2.0×ULN.
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 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	ACRC/ Arizona Clinical Research Center	Tucson	Arizona	United States	85715
2	Yuma Regional Medical Center Cancer Center	Yuma	Arizona	United States	85364
3	Pacific Cancer Medical Center	Anaheim	California	United States	92801
4	Pacific Shores Oncology	Long Beach	California	United States	90813
5	BRCR Medical Center, Inc.	Plantation	Florida	United States	33322
6	Bond & Steele Clinic, P.A.	Winter Haven	Florida	United States	33881
7	Mercy Health Youngstown	Youngstown	Ohio	United States	44501