SPI-2012 vs Pegfilgrastim in the Management of Neutropenia in Participants With Breast Cancer With Docetaxel and Cyclophosphamide (ADVANCE)
- Conditions
- NeutropeniaBreast Cancer
- Interventions
- 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
- 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
- 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)
NEA Baptist Clinic | Fowler Family Center for Cancer Care
🇺🇸Jonesboro, Arkansas, 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
Compassionate Care Research Group, Inc.
🇺🇸Fountain Valley, California, United States
Compassionate Cancer Care Medical Group, Inc
🇺🇸Riverside, California, United States
Carle Cancer Center
🇺🇸Urbana, Illinois, United States
Lakes Research, LLC
🇺🇸Miami Lakes, Florida, United States
Oncology Specialists, SC
🇺🇸Park Ridge, Illinois, United States
West Ky Hematology & Oncology Group, PSC
🇺🇸Paducah, Kentucky, United States
Highland Clinic
🇺🇸Shreveport, Louisiana, United States
Saint Alphonsus Regional Medical Center
🇺🇸Boise, Idaho, United States
Southeast Nebraska Hematology & Oncology Consultants, PC
🇺🇸Lincoln, Nebraska, United States
Waverly Hematology Oncology
🇺🇸Cary, North Carolina, United States
Aultman Hospital
🇺🇸Canton, Ohio, United States
Gabrail Cancer Center Research
🇺🇸Canton, Ohio, United States
Mercy Health Youngstown LLC DBA
🇺🇸Youngstown, Ohio, United States
Cookeville Regional Medical Center
🇺🇸Cookeville, Tennessee, United States
Delta Oncology Associates
🇺🇸Portsmouth, Virginia, United States
West Virginia University
🇺🇸Morgantown, West Virginia, United States
Precision Research Institute, LLC
🇺🇸Chula Vista, California, United States
Compassionate Cancer Care Medical Group, Inc.
🇺🇸Corona, California, United States
Bond Clinic, P.A.
🇺🇸Winter Haven, Florida, United States
Quest Research Institute
🇺🇸Royal Oak, Michigan, United States
Swedish American Cancer Center
🇺🇸Rockford, Illinois, United States
Floyd Memorial Cancer Center of Indiana
🇺🇸New Albany, Indiana, United States
Pacific Cancer Medical Center, Inc.
🇺🇸Anaheim, California, United States
Valley Medical Oncology Consultants
🇺🇸Pleasanton, California, United States
Long Beach Memorial Medical Center
🇺🇸Long Beach, California, United States
Pasco Pinellas Cancer Center
🇺🇸Holiday, Florida, United States
Genesis Cancer Center
🇺🇸Hot Springs, Arkansas, United States
Wellness Oncology Hematology
🇺🇸West Hills, California, United States
Omega Research Consultants LLC
🇺🇸DeBary, Florida, United States
Dwight D. Eisenhower Army Medical Center
🇺🇸Fort Gordon, Georgia, United States
Severance Hospital
🇰🇷Sinchon-dong, Seoul, Korea, Republic of
Jewish General Hospital
🇨🇦Montreal, Quebec, Canada
Franciscan St. Francis Health
🇺🇸Indianapolis, Indiana, United States
St Joseph Heritage Healthcare Institution
🇺🇸Santa Rosa, California, United States
Oncology Institute of Hope and Innovation
🇺🇸Whittier, California, United States
Memorial Health University Medical Center
🇺🇸Savannah, Georgia, United States
Clintell, Inc/Swedish Covenant Hospital
🇺🇸Chicago, Illinois, United States
New Jersey Hematology Oncology Associates
🇺🇸Brick, New Jersey, United States
The Lindner Research Center at the Christ Hospital
🇺🇸Cincinnati, Ohio, United States
Oncology Consultants
🇺🇸Houston, Texas, United States
Methodist Richardson Medical Center- Cancer Center
🇺🇸Richardson, Texas, United States
Northwest Medical Specialties, PLLC
🇺🇸Tacoma, Washington, United States
Arizona Clinical Research Center/ ACRC
🇺🇸Tucson, Arizona, United States
Arizona Center for Cancer Care
🇺🇸Glendale, Arizona, United States
Yuma Regional Medical Center
🇺🇸Yuma, Arizona, United States
Pontchartrain Cancer Center
🇺🇸Covington, Louisiana, United States
Saint Francis Cancer Treatment Center
🇺🇸Grand Island, Nebraska, United States
CHU de Quebec - Universite Laval
🇨🇦Québec, Quebec, Canada
Penobscot Bay Medical Center
🇺🇸Rockport, Maine, United States
AnMed Health Cancer Center
🇺🇸Anderson, South Carolina, United States
Bon Secours Saint Francis Cancer
🇺🇸Greenville, South Carolina, United States
St. Vincent Frontier Cancer Center
🇺🇸Billings, Montana, United States
Forrest General Hospital
🇺🇸Hattiesburg, Mississippi, United States
CISSS de la Montérégie-Centre
🇨🇦Greenfield Park, Quebec, Canada
The West Clinic, PC, d/b/a West Cancer Center
🇺🇸Germantown, Tennessee, United States
Carolina Blood and Cancer Care
🇺🇸Rock Hill, South Carolina, United States
Cha Bundang Medical Center
🇰🇷Seongnam-si, Gyeonggi-do, Korea, Republic of
Florida Cancer Research Institute
🇺🇸Plantation, Florida, United States
AMPM Research Clinic
🇺🇸Miami, Florida, United States
University of Pittsburgh Medical Center (UPMC)
🇺🇸Pittsburgh, Pennsylvania, United States
Ventura County Hematology-Oncology Specialists
🇺🇸Oxnard, California, United States
Freeman Health Systems
🇺🇸Joplin, Missouri, United States
North Shore Hematology Oncology Associates
🇺🇸East Setauket, New York, United States
Pacific Shores Medical Group
🇺🇸Long Beach, California, United States
Mid Florida Hematology and Oncology Centers
🇺🇸Orange City, Florida, United States
Reliant Medical Group
🇺🇸Worcester, Massachusetts, United States
Emad Ibrahim, MD, Inc.
🇺🇸Redlands, California, United States
John B Amos Cancer Center
🇺🇸Columbus, Georgia, United States
Joliet Oncology Hematology Associates
🇺🇸Joliet, Illinois, United States
Northern Indiana Cancer Research Consortium
🇺🇸Westville, Indiana, United States
Ashland-Bellefonte Cancer Center
🇺🇸Ashland, Kentucky, United States
Good Samaritan Hospital Corvallis
🇺🇸Corvallis, Oregon, United States
CHI St. Joseph Health Cancer Center
🇺🇸Bryan, Texas, United States
Texas Oncology, PA
🇺🇸McAllen, Texas, United States
Associates in Hematology and Oncology, PC
🇺🇸Upland, Pennsylvania, United States
Texas Oncology -Methodist Dallas Cancer Center
🇺🇸Dallas, Texas, United States
Northern Utah Associates
🇺🇸Ogden, Utah, United States
RCCA MD LLC/The Center for Cancer and Blood Disorders
🇺🇸Bethesda, Maryland, United States