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

RAnDomized Trial of SPI-2012 Versus Pegfilgrastim in the Management of Chemotherapy Induced Neutropenia in Breast CANCEr Patients Receiving Docetaxel and Cyclophosphamide (TC) (ADVANCE)

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer; Neutropenia
• Intervention / Treatment: Drug: SPI-2012; Drug: Docetaxel; Drug: Cyclophosphamide; Drug: Pegfilgrastim

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).

• Study Type: Interventional
• Enrollment (Actual): 406
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Greenfield Park, Quebec, Canada, J4V 2H1
      • CISSS de la Monteregie-Centre
    • Montreal, Quebec, Canada, H3T 1E2
      • Jewish General Hospital
    • Québec, Quebec, Canada, G1S 4L8
      • CHU de Québec - Université Laval
• Korea, Republic of
  • Gyeonggi-do
    • Seongnam-si, Gyeonggi-do, Korea, Republic of, 13496
      • CHA Bundang Medical Center
  • Seoul
    • Sinchon-dong, Seoul, Korea, Republic of, 03722
      • Severance Hospital
• United States
  • Arizona
    • Glendale, Arizona, United States, 85306
      • Arizona Center for Cancer Care
    • Tucson, Arizona, United States, 85715
      • Arizona Clinical Research Center/ ACRC
    • Yuma, Arizona, United States, 85364
      • Yuma Regional Medical Center
  • Arkansas
    • Hot Springs, Arkansas, United States, 71913
      • Genesis Cancer Center
    • Jonesboro, Arkansas, United States, 72401
      • NEA Baptist Clinic | Fowler Family Center for Cancer Care
  • California
    • Anaheim, California, United States, 92801
      • Pacific Cancer Medical Center, Inc.
    • Bakersfield, California, United States, 93309
      • CBCC Global Research, Inc. at Comprehensive Blood and Cancer Center
    • Berkeley, California, United States, 94704
      • Alta Bates Summit Medical Center
    • Chula Vista, California, United States, 91910
      • Precision Research Institute, LLC
    • Corona, California, United States, 92879
      • Compassionate Cancer Care Medical Group, Inc.
    • Fountain Valley, California, United States, 92708
      • Compassionate Care Research Group, Inc.
    • Long Beach, California, United States, 90813
      • Pacific Shores Medical Group
    • Long Beach, California, United States, 90806
      • Long Beach Memorial Medical Center
    • Oxnard, California, United States, 93030
      • Ventura County Hematology-Oncology Specialists
    • Pleasanton, California, United States, 94588
      • Valley Medical Oncology Consultants
    • Redlands, California, United States, 92373
      • Emad Ibrahim, MD, Inc.
    • Riverside, California, United States, 92501
      • Compassionate Cancer Care Medical Group, Inc
    • Santa Rosa, California, United States, 95403
      • St Joseph Heritage Healthcare Institution
    • West Hills, California, United States, 91307
      • Wellness Oncology Hematology
    • Whittier, California, United States, 90603
      • Oncology Institute of Hope and Innovation
  • Florida
    • DeBary, Florida, United States, 32713
      • Omega Research Consultants LLC
    • Holiday, Florida, United States, 34691
      • Pasco Pinellas Cancer Center
    • Miami, Florida, United States, 33133
      • AMPM Research Clinic
    • Miami Lakes, Florida, United States, 33014
      • Lakes Research, LLC
    • Orange City, Florida, United States, 32763
      • Mid Florida Hematology and Oncology Centers
    • Plantation, Florida, United States, 33324
      • Florida Cancer Research Institute
    • Winter Haven, Florida, United States, 33881
      • Bond Clinic, P.A.
  • Georgia
    • Columbus, Georgia, United States, 31904
      • John B Amos Cancer Center
    • Fort Gordon, Georgia, United States, 30905
      • Dwight D. Eisenhower Army Medical Center
    • Savannah, Georgia, United States, 31404
      • Memorial Health University Medical Center
  • Idaho
    • Boise, Idaho, United States, 83706
      • Saint Alphonsus Regional Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60625
      • Clintell, Inc/Swedish Covenant Hospital
    • Joliet, Illinois, United States, 60435
      • Joliet Oncology Hematology Associates
    • Park Ridge, Illinois, United States, 60068
      • Oncology Specialists, SC
    • Rockford, Illinois, United States, 61114
      • Swedish American Cancer Center
    • Urbana, Illinois, United States, 61801
      • Carle Cancer Center
  • Indiana
    • Indianapolis, Indiana, United States, 46237
      • Franciscan St. Francis Health
    • New Albany, Indiana, United States, 47150
      • Floyd Memorial Cancer Center of Indiana
    • Westville, Indiana, United States, 46391
      • Northern Indiana Cancer Research Consortium
  • Kentucky
    • Ashland, Kentucky, United States, 41101
      • Ashland-Bellefonte Cancer Center
    • Paducah, Kentucky, United States, 42003
      • West Ky Hematology & Oncology Group, PSC
  • Louisiana
    • Covington, Louisiana, United States, 70433
      • Pontchartrain Cancer Center
    • Shreveport, Louisiana, United States, 71105
      • Highland Clinic
  • Maine
    • Rockport, Maine, United States, 04856
      • Penobscot Bay Medical Center
  • Maryland
    • Bethesda, Maryland, United States, 20817
      • RCCA MD LLC/The Center for Cancer and Blood Disorders
  • Massachusetts
    • Worcester, Massachusetts, United States, 01608v
      • Reliant Medical Group
  • Michigan
    • Royal Oak, Michigan, United States, 48073
      • Quest Research Institute
  • Mississippi
    • Hattiesburg, Mississippi, United States, 39401
      • Forrest General Hospital
  • Missouri
    • Joplin, Missouri, United States, 64804
      • Freeman Health Systems
  • Montana
    • Billings, Montana, United States, 59102
      • St. Vincent Frontier Cancer Center
  • Nebraska
    • Grand Island, Nebraska, United States, 68803
      • Saint Francis Cancer Treatment Center
    • Lincoln, Nebraska, United States, 68510
      • Southeast Nebraska Hematology & Oncology Consultants, PC
  • New Jersey
    • Brick, New Jersey, United States, 08724
      • New Jersey Hematology Oncology Associates
  • New York
    • East Setauket, New York, United States, 11733
      • North Shore Hematology Oncology Associates
  • North Carolina
    • Cary, North Carolina, United States, 27518
      • Waverly Hematology Oncology
  • Ohio
    • Canton, Ohio, United States, 44710
      • Aultman Hospital
    • Canton, Ohio, United States, 44718
      • Gabrail Cancer Center Research
    • Cincinnati, Ohio, United States, 45219
      • The Lindner Research Center at The Christ Hospital
    • Youngstown, Ohio, United States, 44504 44501
      • Mercy Health Youngstown LLC DBA
  • Oregon
    • Corvallis, Oregon, United States, 97330
      • Good Samaritan Hospital Corvallis
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Medical Center (UPMC)
    • Upland, Pennsylvania, United States, 19013
      • Associates in Hematology and Oncology, PC
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • AnMed Health Cancer Center
    • Greenville, South Carolina, United States, 29607
      • Bon Secours Saint Francis Cancer
    • Rock Hill, South Carolina, United States, 29732
      • Carolina Blood and Cancer Care
  • Tennessee
    • Cookeville, Tennessee, United States, 38501
      • Cookeville Regional Medical Center
    • Germantown, Tennessee, United States, 38138
      • The West Clinic, PC, d/b/a West Cancer Center
  • Texas
    • Bryan, Texas, United States, 77802
      • CHI St. Joseph Health Cancer Center
    • Dallas, Texas, United States, 75203
      • Texas Oncology -Methodist Dallas Cancer Center
    • Houston, Texas, United States, 77030
      • Oncology Consultants
    • McAllen, Texas, United States, 78503
      • Texas Oncology, PA
    • Richardson, Texas, United States, 75082
      • Methodist Richardson Medical Center- Cancer Center
  • Utah
    • Ogden, Utah, United States, 84403
      • Northern Utah Associates
  • Virginia
    • Portsmouth, Virginia, United States, 23704
      • Delta Oncology Associates
  • Washington
    • Tacoma, Washington, United States, 98405
      • NorthWest Medical Specialties, PLLC
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University

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

Key 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1: SPI-2012 and Docetaxel + Cyclophosphamide (TC); 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.	Drug: SPI-2012; Single-use syringes for subcutaneous injection, administered on Day 2 of each cycle; Other Names: Rolontis®; Eflapegrastim; (HM10460A); Drug: Docetaxel; Standard therapy; Other Names: Taxotere; Drug: Cyclophosphamide; Standard therapy; Other Names: Cytoxan
Experimental: Arm 2: Pegfilgrastim and Docetaxel + Cyclophosphamide (TC); 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.	Drug: Docetaxel; Standard therapy; Other Names: Taxotere; Drug: Cyclophosphamide; Standard therapy; Other Names: Cytoxan; Drug: Pegfilgrastim; Single-dose subcutaneous injection administered on Day 2 of each cycle; Other Names: Neulasta®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Severe Neutropenia (DSN) in Cycle 1	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.	Day 1 and Days 4-15 in Cycle 1 (each cycle was 21 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Absolute Neutrophil Count (ANC) Recovery in Cycle 1	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.	Day 1 and Days 4, 15 in Cycle 1 (each cycle was 21 days)
Depth of Absolute Neutrophil Count (ANC) Nadir in Cycle 1	Depth of ANC Nadir was defined as the lowest ANC value after administration of study drug (SPI-2012 or Pegfilgrastim) in Cycle 1.	Day 1 and Days 4, 15 in Cycle 1 (each cycle was 21 days)
Number of Participants With Febrile Neutropenia (FN) in Cycle 1	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.	Day 1 and Days 4, 15 in Cycle 1 (each cycle was 21 days)
Duration of Severe Neutropenia in Cycle 2, 3 and 4	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.	Days 1, 4, 7, 10, and 15 in cycles 2, 3, and 4 (each cycle was 21 days)
Number of Participants With Neutropenic Complications in Cycle 1	Neutropenic complications refer to hospitalizations due to neutropenic events and/or the use of anti-infectives due to neutropenia.	Day 1 and Days 4, 15 in Cycle 1 (each cycle was 21 days)
Number of Participants With Febrile Neutropenia in Cycles 2, 3, and 4	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.	Days 1, 4, 7, 10, and 15 of Cycles 2, 3, and 4 (each cycle was 21 days)
Relative Dose Intensity (RDI) of TC (Docetaxel + Cyclophosphamide) in Cycles 1 to 4	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.	Cycles 1 to 4 (each cycle was 21 days)
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	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.	From the first dose of TC (Docetaxel + Cyclophosphamide) until 12 months after the last dose of study treatment (up to approximately 34 months)

Collaborators and Investigators

• Sponsor: Spectrum Pharmaceuticals, Inc

Study record dates

Study Major Dates

• Study Start (Actual): January 19, 2016
• Primary Completion (Actual): January 24, 2018
• Study Completion (Actual): October 31, 2018

Study Registration Dates

• First Submitted: December 29, 2015
• First Submitted That Met QC Criteria: December 29, 2015
• First Posted (Estimate): December 31, 2015

Study Record Updates

• Last Update Posted (Actual): March 2, 2022
• Last Update Submitted That Met QC Criteria: February 28, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: Breast Cancer; Early Stage Breast Cancer; Neutropenia; Long-acting Myeloid Growth Factor; Docetaxel + Cyclophosphamide (TC) chemotherapy
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Hematologic Diseases; Breast Diseases; Agranulocytosis; Leukopenia; Leukocyte Disorders; Breast Neoplasms; Neutropenia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Docetaxel; Cyclophosphamide
• Other Study ID Numbers: SPI-GCF-301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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