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

Breast Cancer Clinical Trial

— 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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02643420
• Other study ID #: SPI-GCF-301
• Status: Completed
• Phase: Phase 3
• Start date: January 19, 2016
• Est. completion date: October 31, 2018

Study information

• Verified date: February 2022
• Source: Spectrum Pharmaceuticals, Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 406
• Est. completion date: October 31, 2018
• Est. primary completion date: January 24, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Neutropenia

Intervention

Drug:
• SPI-2012
Single-use syringes for subcutaneous injection, administered on Day 2 of each cycle
• Pegfilgrastim
Single-dose subcutaneous injection administered on Day 2 of each cycle
• Docetaxel
Standard therapy
• Cyclophosphamide
Standard therapy

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Spectrum Pharmaceuticals, Inc

Countries where clinical trial is conducted

United States,  Canada,  Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)