SPI-2012 vs Pegfilgrastim in the Management of Neutropenia in Participants With Breast Cancer With Docetaxel and Cyclophosphamide (ADVANCE)

Phase 3

Completed

Conditions: Neutropenia
Breast Cancer

Interventions: Drug: Pegfilgrastim
Drug: SPI-2012
Drug: Docetaxel
Drug: Cyclophosphamide

Registration Number: NCT02643420

Lead Sponsor: Spectrum Pharmaceuticals, Inc

Brief Summary: The purpose of this study was to compare the efficacy of a single dose of SPI-2012 versus pegfilgrastim in participants with early-stage breast cancer receiving docetaxel and cyclophosphamide (TC), as measured by the duration of severe neutropenia (DSN) in Cycle 1.

Detailed Description: This was a Phase 3, randomized, open-label, active-controlled, multicenter study to compare the efficacy and safety of SPI-2012 vs pegfilgrastim in participants with breast cancer treated with TC chemotherapy.

Each cycle was 21 days. Four cycles were evaluated in this study. On Day 1 of each cycle, participants received TC chemotherapy. On Day 2 of each cycle, participants received study drug (SPI-2012 or pegfilgrastim).

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 406

Inclusion Criteria

New diagnosis of histologically confirmed early-stage breast cancer (ESBC), defined as operable Stage I to Stage IIIA breast cancer
Candidate for adjuvant or neoadjuvant TC chemotherapy
Eastern Cooperative Oncology Group (ECOG) performance score ≤ 2
Absolute neutrophil count (ANC) ≥ 1.5×10^9/L
Platelet count ≥ 100×10^9/L
Hemoglobin > 9 g/dL
Creatinine clearance > 50 mL/min
Total bilirubin ≤ 1.5 mg/dL
Aspartate Aminotransferase per Serum Glutamic-Oxaloacetic Transaminase (AST/SGOT) and Alanine Aminotransferase per Serum Glutamic-Pyruvic Transaminase (ALT/SGPT) ≤ 2.5× Upper Limit of Normal (ULN).
Alkaline phosphatase ≤ 2.0×ULN

Key

Exclusion Criteria

Active concurrent malignancy (except non-melanoma skin cancer or carcinoma in situ of the cervix) or life-threatening disease
Locally recurrent or metastatic breast cancer
Known sensitivity to E. coli -derived products or to any products to be administered during dosing
Concurrent adjuvant cancer therapy
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 anti-infectives, or any serious underlying medical condition that would impair ability to receive protocol treatment
Prior bone marrow or stem cell transplant
Use of 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
Radiation therapy within 30 days prior to enrollment
Major surgery within 30 days prior to enrollment

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 2: Pegfilgrastim and Docetaxel + Cyclophosphamide (TC)	Pegfilgrastim	Participants received pegfilgrastim 6 mg SC injection once per cycle on Day 2 of each cycle up to Cycle 4 (each cycle was 21 days), approximately 24-26 hours after TC chemotherapy administration. TC chemotherapy on Day 1 of each cycle included Docetaxel 75 mg/m\^2 IV infusion and Cyclophosphamide 600 mg/m\^2 IV infusion per institute's standard of care.
Arm 1: SPI-2012 and Docetaxel + Cyclophosphamide (TC)	SPI-2012	Participants received SPI-2012 13.2 milligram (mg)/0.6 milliliter (mL) (3.6 mg Granulocyte Colony-Stimulating Factor \[G-CSF\]) fixed-dose subcutaneous (SC) injection once per cycle on Day 2 of each cycle up to Cycle 4 (each cycle was 21 days), approximately 24-26 hours after TC chemotherapy administration. TC chemotherapy was administered on Day 1 of each cycle and included Docetaxel 75 mg/m\^2 intravenous (IV) infusion and Cyclophosphamide 600 mg/m\^2 IV infusion per institute's standard of care.
Arm 1: SPI-2012 and Docetaxel + Cyclophosphamide (TC)	Cyclophosphamide	Participants received SPI-2012 13.2 milligram (mg)/0.6 milliliter (mL) (3.6 mg Granulocyte Colony-Stimulating Factor \[G-CSF\]) fixed-dose subcutaneous (SC) injection once per cycle on Day 2 of each cycle up to Cycle 4 (each cycle was 21 days), approximately 24-26 hours after TC chemotherapy administration. TC chemotherapy was administered on Day 1 of each cycle and included Docetaxel 75 mg/m\^2 intravenous (IV) infusion and Cyclophosphamide 600 mg/m\^2 IV infusion per institute's standard of care.
Arm 1: SPI-2012 and Docetaxel + Cyclophosphamide (TC)	Docetaxel	Participants received SPI-2012 13.2 milligram (mg)/0.6 milliliter (mL) (3.6 mg Granulocyte Colony-Stimulating Factor \[G-CSF\]) fixed-dose subcutaneous (SC) injection once per cycle on Day 2 of each cycle up to Cycle 4 (each cycle was 21 days), approximately 24-26 hours after TC chemotherapy administration. TC chemotherapy was administered on Day 1 of each cycle and included Docetaxel 75 mg/m\^2 intravenous (IV) infusion and Cyclophosphamide 600 mg/m\^2 IV infusion per institute's standard of care.
Arm 2: Pegfilgrastim and Docetaxel + Cyclophosphamide (TC)	Cyclophosphamide	Participants received pegfilgrastim 6 mg SC injection once per cycle on Day 2 of each cycle up to Cycle 4 (each cycle was 21 days), approximately 24-26 hours after TC chemotherapy administration. TC chemotherapy on Day 1 of each cycle included Docetaxel 75 mg/m\^2 IV infusion and Cyclophosphamide 600 mg/m\^2 IV infusion per institute's standard of care.
Arm 2: Pegfilgrastim and Docetaxel + Cyclophosphamide (TC)	Docetaxel	Participants received pegfilgrastim 6 mg SC injection once per cycle on Day 2 of each cycle up to Cycle 4 (each cycle was 21 days), approximately 24-26 hours after TC chemotherapy administration. TC chemotherapy on Day 1 of each cycle included Docetaxel 75 mg/m\^2 IV infusion and Cyclophosphamide 600 mg/m\^2 IV infusion per institute's standard of care.

Primary Outcome Measures

Name	Time	Method
Duration of Severe Neutropenia (DSN) in Cycle 1	Day 1 and Days 4-15 in Cycle 1 (each cycle was 21 days)	DSN was defined as the number of days of severe neutropenia (absolute neutrophil count \[ANC\] \<0.5×10\^9/L), after the administration of study drug in Cycle 1.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Febrile Neutropenia (FN) in Cycle 1	Day 1 and Days 4, 15 in Cycle 1 (each cycle was 21 days)	FN was defined as an oral temperature \> 38.3 degrees Celsius (C) (101.0 degrees Fahrenheit \[F\]) or two consecutive readings of \>=38.0 degrees C (100.4 degrees F) for 2 hours and ANC \<1.0×10\^9/L.
Depth of Absolute Neutrophil Count (ANC) Nadir in Cycle 1	Day 1 and Days 4, 15 in Cycle 1 (each cycle was 21 days)	Depth of ANC Nadir was defined as the lowest ANC value after administration of study drug (SPI-2012 or Pegfilgrastim) in Cycle 1.
Number of Participants With Febrile Neutropenia in Cycles 2, 3, and 4	Days 1, 4, 7, 10, and 15 of Cycles 2, 3, and 4 (each cycle was 21 days)	FN was defined as an oral temperature \> 38.3 degrees C (101.0 degrees Fahrenheit \[F\]) or two consecutive readings of \>=38.0 degrees C (100.4 degrees F) for 2 hours and ANC \<1.0×10\^9/L.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	From the first dose of TC (Docetaxel + Cyclophosphamide) until 12 months after the last dose of study treatment (up to approximately 34 months)	An adverse event (AE) is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product or study procedure, whether or not considered related to the medicinal product. A TEAE for Treatment Period is defined as adverse event with an onset date on or after the date of study drug administration through the end of treatment. TEAE for follow up is defined as any new onset or ongoing AE at the end of Treatment. SAE is defined as any AE which meets any of the following criteria: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in a persistent or significant disability/incapacity, results in a congenital anomaly/birth defect, includes important medical events.
Time to Absolute Neutrophil Count (ANC) Recovery in Cycle 1	Day 1 and Days 4, 15 in Cycle 1 (each cycle was 21 days)	Time to ANC Recovery was defined as the time from chemotherapy administration until ANC increased to ≥1.5×10\^9/L after the expected nadir within Cycle 1. Time to ANC recovery was assigned as 0 for participants whose ANC value never dropped below 1.5 x10\^9/L.
Relative Dose Intensity (RDI) of TC (Docetaxel + Cyclophosphamide) in Cycles 1 to 4	Cycles 1 to 4 (each cycle was 21 days)	RDI was defined as the percentage of the planned dose that each participant actually received during the study, expressed as the total dose received, divided by the total dose planned and multiplied by 100. The planned dose was defined as the dose that would be given if no doses were missed and/or no dose reductions were made for the number of cycles started. The total planned dose was the sum of planned doses over all cycles.
Duration of Severe Neutropenia in Cycle 2, 3 and 4	Days 1, 4, 7, 10, and 15 in cycles 2, 3, and 4 (each cycle was 21 days)	DSN was defined as the number of days of severe neutropenia (ANC \<0.5×10\^9 /L) from the first occurrence of an ANC below the threshold in Cycles 2, 3, and 4.
Number of Participants With Neutropenic Complications in Cycle 1	Day 1 and Days 4, 15 in Cycle 1 (each cycle was 21 days)	Neutropenic complications refer to hospitalizations due to neutropenic events and/or the use of anti-infectives due to neutropenia.

Trial Locations

Locations (81): Arizona Center for Cancer Care
🇺🇸
Glendale, Arizona, United States
Arizona Clinical Research Center/ ACRC
🇺🇸
Tucson, Arizona, United States
Yuma Regional Medical Center
🇺🇸
Yuma, Arizona, United States
Genesis Cancer Center
🇺🇸
Hot Springs, Arkansas, United States
NEA Baptist Clinic | Fowler Family Center for Cancer Care
🇺🇸
Jonesboro, Arkansas, United States
Pacific Cancer Medical Center, Inc.
🇺🇸
Anaheim, California, United States
CBCC Global Research, Inc. at Comprehensive Blood and Cancer Center
🇺🇸
Bakersfield, California, United States
Alta Bates Summit Medical Center
🇺🇸
Berkeley, California, United States
Precision Research Institute, LLC
🇺🇸
Chula Vista, California, United States
Compassionate Cancer Care Medical Group, Inc.
🇺🇸
Corona, California, United States
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Arizona Center for Cancer Care
🇺🇸Glendale, Arizona, United States