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

• ClinicalTrials.gov Identifier: NCT04187898
• Recruitment Status: Active, not recruiting
• First Posted: December 5, 2019
• Last Update Posted: May 16, 2024
• Sponsor: Spectrum Pharmaceuticals, Inc
• Information provided by (Responsible Party): Spectrum Pharmaceuticals, Inc

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	Biological: 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.

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 50 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• 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.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: March 11, 2020
• Estimated Primary Completion Date: July 31, 2024
• Estimated Study Completion Date: July 31, 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Early Phase: Eflapegrastim @ 30mins post TC; 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; Administered in Cycle 1, 30 minutes after TC chemotherapy. Administered in Cycles 2-4, on day 2 of each cycle.; Drug: Docetaxel; 75 mg/m^2 IV infusion. Administered on Day 1 of each cycle.; Other Name: Taxotere; Drug: Cyclophosphamide; 600 mg/m^2 IV infusion. Administered on Day 1 of each cycle.; Other Name: Cytoxan
Experimental: Early Phase: 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. Each cycle is 21 days.	Biological: Eflapegrastim; Administered in Cycle 1, 3 hours after TC chemotherapy. Administered in Cycles 2-4, on day 2 of each cycle.; Drug: Docetaxel; 75 mg/m^2 IV infusion. Administered on Day 1 of each cycle.; Other Name: Taxotere; Drug: Cyclophosphamide; 600 mg/m^2 IV infusion. Administered on Day 1 of each cycle.; Other Name: Cytoxan
Experimental: Early Phase: 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. Each cycle is 21 days.	Biological: Eflapegrastim; Administered in Cycle 1, 5 hours after TC chemotherapy. Administered in Cycles 2-4, on day 2 of each cycle.; Drug: Docetaxel; 75 mg/m^2 IV infusion. Administered on Day 1 of each cycle.; Other Name: Taxotere; Drug: Cyclophosphamide; 600 mg/m^2 IV infusion. Administered on Day 1 of each cycle.; Other Name: Cytoxan
Experimental: Expansion Phase: Eflapegrastim @ 30 mins 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. 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; Administered in Cycles 1-4, 30 mins after TC chemotherapy.; Drug: Docetaxel; 75 mg/m^2 IV infusion. Administered on Day 1 of each cycle.; Other Name: Taxotere; Drug: Cyclophosphamide; 600 mg/m^2 IV infusion. Administered on Day 1 of each cycle.; Other Name: Cytoxan

Outcome Measures

Primary Outcome Measures :

1. Time to Recovery of Absolute Neutrophil Count (ANC) From Nadir to ≥1.5×10^9/L in Cycle 1 [ Time Frame: Cycle 1 is 21 days ]
   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 :

1. Duration of Grade 4 Neutropenia (DSN) in Cycle 1 [ Time Frame: Cycle 1 is 21 days ]
   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.
2. Proportion of Patients With Grade 4 Neutropenia in Cycle 1 [ Time Frame: Cycle 1 is 21 days ]
3. Incidence of Grade 3 Febrile Neutropenia (FN) in Cycle 1 [ Time Frame: 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 Celsius (101.0 Fahrenheit [F]) or a sustained temperature of >38.0 degrees Celsius (100.4 F).
4. 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 ]
5. Expansion Phase: Time to Recovery of ANC From Nadir to ≥1.5×10^9/L in Cycles 2-4 [ Time Frame: Cycles 2-4 (cycle length=21 days) (up to approximately 63 days) ]
   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.
6. Expansion Phase: DSN in Cycles 2-4 [ Time Frame: Cycles 2-4 (cycle length=21 days) (up to approximately 63 days) ]
   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.
7. Expansion Phase: Proportion of Patients With Grade 4 Neutropenia in Cycles 2-4 [ Time Frame: Cycles 2-4 (cycle length=21 days) (up to approximately 63 days) ]
8. Expansion Phase: Incidence of FN in Cycles 2-4 [ Time Frame: Cycles 2-4 (cycle length=21 days) (up to approximately 63 days) ]
   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).
9. Expansion Phase: Incidence of Neutropenic Complications, Including Hospitalization due to Neutropenia, FN, and use of Anti-infectives During Cycles 2-4 [ Time Frame: Cycles 2-4 (cycle length=21 days) (up to approximately 63 days) ]
10. Number of Patients With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) as a Measure of Safety [ Time Frame: Up to approximately 40 days after the last dose of study treatment or early study discontinuation (up to approximately 4 months) ]
11. Proportion of Patients Discontinuing Because of a TEAE [ Time Frame: Up to approximately 40 days after the last dose of study treatment or early study discontinuation (up to approximately 4 months) ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Arizona

ACRC/ Arizona Clinical Research Center

Tucson, Arizona, United States, 85715

Yuma Regional Medical Center Cancer Center

Yuma, Arizona, United States, 85364

United States, California

Pacific Cancer Medical Center

Anaheim, California, United States, 92801

City of Hope

Long Beach, California, United States, 90813

United States, Florida

BRCR Medical Center, Inc.

Plantation, Florida, United States, 33322

Bond & Steele Clinic, P.A.

Winter Haven, Florida, United States, 33881

United States, Montana

SCL Health Research Institute, Inc.

Billings, Montana, United States, 59102

United States, Ohio

Mercy Health Youngstown

Youngstown, Ohio, United States, 44501

Sponsors and Collaborators

Spectrum Pharmaceuticals, Inc

More Information

• Responsible Party: Spectrum Pharmaceuticals, Inc
• ClinicalTrials.gov Identifier: NCT04187898
• Other Study ID Numbers: SPI-GCF-104
• First Posted: December 5, 2019
• Last Update Posted: May 16, 2024
• Last Verified: May 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by Spectrum Pharmaceuticals, Inc:

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

Additional relevant MeSH terms:

Breast Neoplasms; Neutropenia; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Agranulocytosis; Leukopenia; Cytopenia; Hematologic Diseases; Leukocyte Disorders; Cyclophosphamide; Docetaxel; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Myeloablative Agonists; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators