Clinical trial NCT04187898: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neutropenia
Breast Cancer
Keywords: Neutropenia
Early Stage Breast Cancer
Long-acting Myeloid Growth Factor
Docetaxel + Cyclophosphamide (TC) Chemotherapy
Lead sponsor: Spectrum Pharmaceuticals, Inc
Sponsor class: INDUSTRY
First posted: 2019-12-05
Enrollment: 59
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention 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.
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Time to Recovery of Absolute Neutrophil Count (ANC) From Nadir to ≥1.5×10^9/L in Cycle 1
timeFrame: Cycle 1 is 21 days
Secondary outcomes:
measure: Duration of Grade 4 Neutropenia (DSN) in Cycle 1
timeFrame: Cycle 1 is 21 days
measure: Proportion of Patients With Grade 4 Neutropenia in Cycle 1
timeFrame: Cycle 1 is 21 days
measure: Incidence of Grade 3 Febrile Neutropenia (FN) in Cycle 1
timeFrame: Cycle 1 is 21 days
measure: Incidence of Neutropenic Complications, Including Hospitalization due to Neutropenia, FN, and use of Anti-infectives During Cycle 1
timeFrame: Cycle 1 is 21 days
measure: Expansion Phase: Time to Recovery of ANC From Nadir to ≥1.5×10^9/L in Cycles 2-4
timeFrame: Cycles 2-4 (cycle length=21 days) (up to approximately 63 days)
measure: Expansion Phase: DSN in Cycles 2-4
timeFrame: Cycles 2-4 (cycle length=21 days) (up to approximately 63 days)
measure: Expansion Phase: Proportion of Patients With Grade 4 Neutropenia in Cycles 2-4
timeFrame: Cycles 2-4 (cycle length=21 days) (up to approximately 63 days)
measure: Expansion Phase: Incidence of FN in Cycles 2-4
timeFrame: Cycles 2-4 (cycle length=21 days) (up to approximately 63 days)
measure: Expansion Phase: Incidence of Neutropenic Complications, Including Hospitalization due to Neutropenia, FN, and use of Anti-infectives During Cycles 2-4
timeFrame: Cycles 2-4 (cycle length=21 days) (up to approximately 63 days)
measure: Number of Patients With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) as a Measure of Safety
timeFrame: Up to approximately 40 days after the last dose of study treatment or early study discontinuation (up to approximately 4 months)
measure: Proportion of Patients Discontinuing Because of a TEAE
timeFrame: Up to approximately 40 days after the last dose of study treatment or early study discontinuation (up to approximately 4 months)
Other outcomes:
Locations:
city: Tucson
country: United States
facility: ACRC/ Arizona Clinical Research Center
state: Arizona
city: Yuma
country: United States
facility: Yuma Regional Medical Center Cancer Center
state: Arizona
city: Anaheim
country: United States
facility: Pacific Cancer Medical Center
state: California
city: Long Beach
country: United States
facility: City of Hope
state: California
city: Plantation
country: United States
facility: BRCR Medical Center, Inc.
state: Florida
city: Winter Haven
country: United States
facility: Bond & Steele Clinic, P.A.
state: Florida
city: Billings
country: United States
facility: SCL Health Research Institute, Inc.
state: Montana
city: Youngstown
country: United States
facility: Mercy Health Youngstown
state: Ohio
Study officials:
References: