Pharmacokinetics of SPI-2012 (Eflapegrastim) in Breast Cancer Patients Receiving Docetaxel and Cyclophosphamide (TC) Chemotherapy

The purpose of this study is to evaluate the pharmacokinetic (PK) profile of a fixed dose of SPI-2012 in patients with early-stage breast cancer receiving docetaxel and cyclophosphamide (TC) chemotherapy, as measured by the serum concentration of SPI-2012 on specific days following drug administration.

Study Overview

• Status: Completed
• Conditions: Breast Cancer; Pharmacokinetics
• Intervention / Treatment: Drug: SPI-2012

Detailed Description

This is a Phase 1, single-arm multicenter study to evaluate the PK and safety of SPI-2012 (a long acting myeloid growth factor) in breast cancer patients treated with TC chemotherapy.

Approximately 25 patients will be enrolled.

Each cycle will be 21 days and patients will receive 4 cycles of treatment with 2 additional cycles based on the investigator's discretion. On Day 1 of each cycle, patients will receive TC chemotherapy and on Day 2 of each cycle, patients will receive SPI-2012.

Pharmacokinetics will be evaluated only in Cycles 1 and 3.

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Anaheim, California, United States, 92804
      • Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Newly diagnosed, histologically confirmed early-stage breast cancer, defined as operable Stage I to Stage IIIA breast cancer.
• Candidate to receive adjuvant or neoadjuvant TC chemotherapy.
• ANC ≥1.5x10^9/L
• Platelet count ≥100x10^9/L
• Hemoglobin >9 g/dL
• Calculated creatinine clearance >50 mL/min
• Total bilirubin ≤1.5 mg/dL
• AST and ALT ≤2.5xULN
• Alkaline phosphatase ≤2.0xULN
• ECOG ≤2

Exclusion Criteria:

• Active concurrent malignancy (except non melanoma skin cancer or carcinoma in situ of cervix) or life-threatening disease. If history of prior malignancies or contralateral breast cancer, must be disease free for at least 5 years.
• Known sensitivity to E. coli derived products or known sensitivity to any of the products to be administered during dosing.
• Concurrent adjuvant cancer therapy.
• Locally recurrent/metastatic breast cancer.
• Previous exposure to filgrastim, pegfilgrastim, or other G-CSF products in clinical development within 12 months prior to the administration of study drug.
• Active infection, receiving antibiotics or any serious underlying medical condition which would impair the ability of the patient to receive protocol-specified treatment.
• Prior bone marrow or hematopoietic stem cell transplant
• 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 radiation therapy within 30 days prior to enrollment.
• Major surgery within 30 days prior to enrollment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SPI-2012; SPI-2012 (13.2 mg/0.6 mL fixed dose, equivalent to 3.6 mg G-CSF per cycle); Supplied in 1 mL prefilled, single-use syringes for subcutaneous injection; Administered on Day 2 of each cycle after TC administration	Drug: SPI-2012; Supplied in prefilled, single-use syringes for subcutaneous injection and administered on Day 2 of each cycle.; Other Names: Eflapegrastim; Rolontis™

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak Plasma Concentration (Cmax)	PK samples will be collected at predetermined time intervals and Peak Concentration is measured at highest value among all concentrations.	Up to 42 days
Area under the plasma concentration versus time curve (AUC)	PK samples will be collected at predetermined time intervals. AUC is calculated in the plot of plasma concentration versus time curve	Up to 42 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with treatment-related adverse events as assessed by CTCAE v4.03	An AE is defined as any untoward medical occurrence in a patient or clinical investigation patient, temporally associated with the use of a medicinal product or study procedure, whether or not considered related to the medicinal product. A treatment-emergent AE (TEAE) is any AE that occurs from the first dose of study treatment through 35 (±5) days after the date of patient early discontinuation.	6 months
Population slope of the relationship between the change from baseline in QTc intervals and plasma concentrations of SPI-2012	A linear mixed effects modeling approach will be used to quantify the relationship between the plasma concentrations of SPI-2012 and change from baseline in QT intervals (∆QTc). Plasma concentration, intercept, and subject are to be included as random effects.	Up to 42 days

Collaborators and Investigators

• Sponsor: Spectrum Pharmaceuticals, Inc

Study record dates

Study Major Dates

• Study Start (Actual): May 11, 2017
• Primary Completion (Actual): February 19, 2018
• Study Completion (Actual): May 18, 2018

Study Registration Dates

• First Submitted: April 20, 2017
• First Submitted That Met QC Criteria: April 26, 2017
• First Posted (Actual): May 2, 2017

Study Record Updates

• Last Update Posted (Actual): November 13, 2020
• Last Update Submitted That Met QC Criteria: November 11, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: Breast Cancer; Pharmacokinetics; Early Stage Breast Cancer; Long-acting Myeloid Growth Factor; Docetaxel + Cyclophosphamide (TC) Chemotherapy
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: SPI-GCF-301-PK

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No