Clinical trial NCT02643420: SPI-2012 vs Pegfilgrastim in the Management of Neutropenia in Participants With Breast Cancer With Docetaxel and Cyclophosphamide (ADVANCE)
Official title: RAnDomized Trial of SPI-2012 Versus Pegfilgrastim in the Management of Chemotherapy Induced Neutropenia in Breast CANCEr Patients Receiving Docetaxel and Cyclophosphamide (TC) (ADVANCE)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Neutropenia
Breast Cancer
Keywords: Neutropenia
Breast Cancer
Long-acting Myeloid Growth Factor
Early Stage Breast Cancer
Docetaxel + Cyclophosphamide (TC) chemotherapy
Lead sponsor: Spectrum Pharmaceuticals, Inc
Sponsor class: INDUSTRY
First posted: 2015-12-31
Enrollment: 406
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Eligibility criteria: 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

Primary outcomes:
measure: Duration of Severe Neutropenia (DSN) in Cycle 1
timeFrame: Day 1 and Days 4-15 in Cycle 1 (each cycle was 21 days)
Secondary outcomes:
measure: Time to Absolute Neutrophil Count (ANC) Recovery in Cycle 1
timeFrame: Day 1 and Days 4, 15 in Cycle 1 (each cycle was 21 days)
measure: Depth of Absolute Neutrophil Count (ANC) Nadir in Cycle 1
timeFrame: Day 1 and Days 4, 15 in Cycle 1 (each cycle was 21 days)
measure: Number of Participants With Febrile Neutropenia (FN) in Cycle 1
timeFrame: Day 1 and Days 4, 15 in Cycle 1 (each cycle was 21 days)
measure: Duration of Severe Neutropenia in Cycle 2, 3 and 4
timeFrame: Days 1, 4, 7, 10, and 15 in cycles 2, 3, and 4 (each cycle was 21 days)
measure: Number of Participants With Neutropenic Complications in Cycle 1
timeFrame: Day 1 and Days 4, 15 in Cycle 1 (each cycle was 21 days)
measure: Number of Participants With Febrile Neutropenia in Cycles 2, 3, and 4
timeFrame: Days 1, 4, 7, 10, and 15 of Cycles 2, 3, and 4 (each cycle was 21 days)
measure: Relative Dose Intensity (RDI) of TC (Docetaxel + Cyclophosphamide) in Cycles 1 to 4
timeFrame: Cycles 1 to 4 (each cycle was 21 days)
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: From the first dose of TC (Docetaxel + Cyclophosphamide) until 12 months after the last dose of study treatment (up to approximately 34 months)
Other outcomes:
Locations:
city: Glendale
country: United States
facility: Arizona Center for Cancer Care
state: Arizona
city: Tucson
country: United States
facility: Arizona Clinical Research Center/ ACRC
state: Arizona
city: Yuma
country: United States
facility: Yuma Regional Medical Center
state: Arizona
city: Hot Springs
country: United States
facility: Genesis Cancer Center
state: Arkansas
city: Jonesboro
country: United States
facility: NEA Baptist Clinic | Fowler Family Center for Cancer Care
state: Arkansas
city: Anaheim
country: United States
facility: Pacific Cancer Medical Center, Inc.
state: California
city: Bakersfield
country: United States
facility: CBCC Global Research, Inc. at Comprehensive Blood and Cancer Center
state: California
city: Berkeley
country: United States
facility: Alta Bates Summit Medical Center
state: California
city: Chula Vista
country: United States
facility: Precision Research Institute, LLC
state: California
city: Corona
country: United States
facility: Compassionate Cancer Care Medical Group, Inc.
state: California
city: Fountain Valley
country: United States
facility: Compassionate Care Research Group, Inc.
state: California
city: Long Beach
country: United States
facility: Long Beach Memorial Medical Center
state: California
city: Long Beach
country: United States
facility: Pacific Shores Medical Group
state: California
city: Oxnard
country: United States
facility: Ventura County Hematology-Oncology Specialists
state: California
city: Pleasanton
country: United States
facility: Valley Medical Oncology Consultants
state: California
city: Redlands
country: United States
facility: Emad Ibrahim, MD, Inc.
state: California
city: Riverside
country: United States
facility: Compassionate Cancer Care Medical Group, Inc
state: California
city: Santa Rosa
country: United States
facility: St Joseph Heritage Healthcare Institution
state: California
city: West Hills
country: United States
facility: Wellness Oncology Hematology
state: California
city: Whittier
country: United States
facility: Oncology Institute of Hope and Innovation
state: California
city: DeBary
country: United States
facility: Omega Research Consultants LLC
state: Florida
city: Holiday
country: United States
facility: Pasco Pinellas Cancer Center
state: Florida
city: Miami Lakes
country: United States
facility: Lakes Research, LLC
state: Florida
city: Miami
country: United States
facility: AMPM Research Clinic
state: Florida
city: Orange City
country: United States
facility: Mid Florida Hematology and Oncology Centers
state: Florida
city: Plantation
country: United States
facility: Florida Cancer Research Institute
state: Florida
city: Winter Haven
country: United States
facility: Bond Clinic, P.A.
state: Florida
city: Columbus
country: United States
facility: John B Amos Cancer Center
state: Georgia
city: Fort Gordon
country: United States
facility: Dwight D. Eisenhower Army Medical Center
state: Georgia
city: Savannah
country: United States
facility: Memorial Health University Medical Center
state: Georgia
city: Boise
country: United States
facility: Saint Alphonsus Regional Medical Center
state: Idaho
city: Chicago
country: United States
facility: Clintell, Inc/Swedish Covenant Hospital
state: Illinois
city: Joliet
country: United States
facility: Joliet Oncology Hematology Associates
state: Illinois
city: Park Ridge
country: United States
facility: Oncology Specialists, SC
state: Illinois
city: Rockford
country: United States
facility: Swedish American Cancer Center
state: Illinois
city: Urbana
country: United States
facility: Carle Cancer Center
state: Illinois
city: Indianapolis
country: United States
facility: Franciscan St. Francis Health
state: Indiana
city: New Albany
country: United States
facility: Floyd Memorial Cancer Center of Indiana
state: Indiana
city: Westville
country: United States
facility: Northern Indiana Cancer Research Consortium
state: Indiana
city: Ashland
country: United States
facility: Ashland-Bellefonte Cancer Center
state: Kentucky
city: Paducah
country: United States
facility: West Ky Hematology & Oncology Group, PSC
state: Kentucky
city: Covington
country: United States
facility: Pontchartrain Cancer Center
state: Louisiana
city: Shreveport
country: United States
facility: Highland Clinic
state: Louisiana
city: Rockport
country: United States
facility: Penobscot Bay Medical Center
state: Maine
city: Bethesda
country: United States
facility: RCCA MD LLC/The Center for Cancer and Blood Disorders
state: Maryland
city: Worcester
country: United States
facility: Reliant Medical Group
state: Massachusetts
city: Royal Oak
country: United States
facility: Quest Research Institute
state: Michigan
city: Hattiesburg
country: United States
facility: Forrest General Hospital
state: Mississippi
city: Joplin
country: United States
facility: Freeman Health Systems
state: Missouri
city: Billings
country: United States
facility: St. Vincent Frontier Cancer Center
state: Montana
city: Grand Island
country: United States
facility: Saint Francis Cancer Treatment Center
state: Nebraska
city: Lincoln
country: United States
facility: Southeast Nebraska Hematology & Oncology Consultants, PC
state: Nebraska
city: Brick
country: United States
facility: New Jersey Hematology Oncology Associates
state: New Jersey
city: East Setauket
country: United States
facility: North Shore Hematology Oncology Associates
state: New York
city: Cary
country: United States
facility: Waverly Hematology Oncology
state: North Carolina
city: Canton
country: United States
facility: Aultman Hospital
state: Ohio
city: Canton
country: United States
facility: Gabrail Cancer Center Research
state: Ohio
city: Cincinnati
country: United States
facility: The Lindner Research Center at the Christ Hospital
state: Ohio
city: Youngstown
country: United States
facility: Mercy Health Youngstown LLC DBA
state: Ohio
city: Corvallis
country: United States
facility: Good Samaritan Hospital Corvallis
state: Oregon
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center (UPMC)
state: Pennsylvania
city: Upland
country: United States
facility: Associates in Hematology and Oncology, PC
state: Pennsylvania
city: Anderson
country: United States
facility: AnMed Health Cancer Center
state: South Carolina
city: Greenville
country: United States
facility: Bon Secours Saint Francis Cancer
state: South Carolina
city: Rock Hill
country: United States
facility: Carolina Blood and Cancer Care
state: South Carolina
city: Cookeville
country: United States
facility: Cookeville Regional Medical Center
state: Tennessee
city: Germantown
country: United States
facility: The West Clinic, PC, d/b/a West Cancer Center
state: Tennessee
city: Bryan
country: United States
facility: CHI St. Joseph Health Cancer Center
state: Texas
city: Dallas
country: United States
facility: Texas Oncology -Methodist Dallas Cancer Center
state: Texas
city: Houston
country: United States
facility: Oncology Consultants
state: Texas
city: McAllen
country: United States
facility: Texas Oncology, PA
state: Texas
city: Richardson
country: United States
facility: Methodist Richardson Medical Center- Cancer Center
state: Texas
city: Ogden
country: United States
facility: Northern Utah Associates
state: Utah
city: Portsmouth
country: United States
facility: Delta Oncology Associates
state: Virginia
city: Tacoma
country: United States
facility: Northwest Medical Specialties, PLLC
state: Washington
city: Morgantown
country: United States
facility: West Virginia University
state: West Virginia
city: Greenfield Park
country: Canada
facility: CISSS de la Montérégie-Centre
state: Quebec
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Québec
country: Canada
facility: CHU de Quebec - Universite Laval
state: Quebec
city: Seongnam-si
country: Korea, Republic of
facility: Cha Bundang Medical Center
state: Gyeonggi-do
city: Sinchon-dong
country: Korea, Republic of
facility: Severance Hospital
state: Seoul
Study officials:
References: