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

Breast Cancer Clinical Trial

Official title:

Randomized, OpEn-Label, Active-ContrOl Trial of SPI-2012 (Eflapegrastim) Versus Pegfilgrastim in the Management of Chemotherapy-Induced Neutropenia in Early-Stage BReast Cancer Patients Receiving Docetaxel and Cyclophosphamide (TC) (RECOVER)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02953340
• Other study ID #: SPI-GCF-302
• Secondary ID: 2016-003469-24
• Status: Completed
• Phase: Phase 3
• Start date: May 10, 2017
• Est. completion date: May 6, 2019

Study information

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

Clinical Trial Summary

The purpose of this study is to compare the efficacy 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).

Description:

This is a Phase 3, randomized, open-label, active-controlled, multicenter study to compare the efficacy and safety of SPI-2012 versus pegfilgrastim in participants with early-stage breast cancer treated with TC chemotherapy as measured by the duration of severe neutropenia (DSN).

Each cycle was 21 days. Four cycles were evaluated for 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).

After cycle 1, as applicable, participants who received at least one dose of study drug will be followed for safety for 12 months after the last dose of study treatment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 237
• Est. completion date: May 6, 2019
• Est. primary completion date: June 8, 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 neo-adjuvant TC chemotherapy

• Eastern Cooperative Oncology Group (ECOG) performance status <= 2

• Absolute neutrophil count (ANC) >=1.5×10^9/L

• Platelet count >=100×10^9/L

• Hemoglobin >9 g/dL

• Calculated creatinine clearance > 50 mL/min

• Total bilirubin <=1.5 mg/dL

• Aspartate aminotransferase (AST) / Serum glutamic oxaloacetic transaminase (SGOT) and Alanine aminotransferase (ALT)/Serum glutamic pyruvic transaminase (SGPT) <=2.5×ULN (upper limit of normal)

• 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/metastatic breast cancer

• Known sensitivity to E. coli-derived products

• 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 underlying medical condition that would impair ability to receive protocol treatment

• Prior bone marrow or stem cell transplant

• Used 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
Supplied in prefilled single-use syringes for subcutaneous injection, administered on Day 2 of each cycle
• Pegfilgrastim
Subcutaneous injection administered on Day 2 of each cycle.
• Docetaxel
75mg/m^2 IV infusion administered on Day 1 of each cycle
• Cyclophosphamide
600mg/m^2 IV infusion administered on Day 1 of each cycle

Locations

Country	Name	City	State
Canada	CISSS de la Montérégie-Centre	Longueuil	Quebec
Canada	Jewish General Hospital	Montreal	Quebec
Hungary	Magyar Honvedseg Egeszsegugyi Kozpont, Onkologiai Osztaly	Budapest
Hungary	Orszagos Onkologiai Intezet, ""B"" Belgyogyaszati Onkologiai Osztaly	Budapest
Hungary	Szent Imre Egyetemi Oktatokorhaz, Klinikai Onkologiai Osztaly	Budapest
Hungary	Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi Okato Korhaz, Klinikai Onkologiai es Sugarterapias Centrum	Miskolc
Hungary	Szabolcs-Szatmar-Bereg Megyei Korhazak, Egyetemi Oktato Korhaz, Onkoradiologiai Osztaly	Nyíregyháza
Hungary	Tolna Megyei Balassa Janos Korhaz, Klinikai Onkologiai Osztaly	Szekszard
India	KEM Hospital Research Centre	Pune	Maharashtra
India	Christian Medical College	Vellore	Tamil Nadu
Korea, Republic of	Seoul National University Hospital	Daehwa-ro	Jongno-gu Seoul
Korea, Republic of	National Cancer Center	IIsan-ro	Gyeonggi-do
Korea, Republic of	Wonju Severance Christian Hospital	Ilsan-ro	Gangwon-do
Korea, Republic of	Korea University Anam Hospital	Inchon-ro	Seongbuk-guSeoul
Korea, Republic of	Inha University Hospital	Inhang-ro	Jung-guIncheon
Korea, Republic of	Samsung Medical Center	Irwon-ro	Gangnam-gu Seoul
Korea, Republic of	Cha Bundang Medical Center	Yatap-ro	Gyeonggi-do
Korea, Republic of	Severance Hospital	Yonsei-ro	Seoul
Poland	BIALOSTOCKIE CENTRUM ONKOLOGII im. Marii Sklodowskiej-Curie Oddzial Onkologii Klinicznej im. Ewy Pileckiej z Pododdzialem Chemioterapii dziennej	Bialystok
Poland	Regionalny Szpital Specjalistyczny im. dr Wladyslawa Bieganskiego Oddzial Onkologii Klinicznej	Grudziadz
Poland	Instytut Centrum Zdrowia Matki Polki Klinika Chirurgii Onkologicznej i Chorob Piersi z Pododdzialem Onkologii Klinicznej	Lodz
Poland	Pracownia Leku Cytotoksycznego Szpitala Klinicznego Przemienienia Panskiego UM im. Karola Marcinkowskiego w Poznaniu	Poznan
Poland	Szpital Rejonowy im. Dr. Jozefa Rostka w Raciborzu Dzienny Oddzial Chemioterapii	Racibórz
Poland	MrukMed. Lekarz Beata Madej Mruk i Partner. Spolka Partnerska Oddzial nr 1 w Rzeszowie	Rzeszow
Poland	Zachodniopomorskie Centrum Onkologii Osrodek Innowacyjnosci, Rozwoju i Badan Klinicznych	Szczecin
United States	Pacific Cancer Medical Center, Inc.	Anaheim	California
United States	St. Vincent Frontier Cancer Center	Billings	Montana
United States	Saint Alphonsus Regional Medical Center	Boise	Idaho
United States	CHI St Joseph Health Cancer Center	Bryan	Texas
United States	Aultman Hospital	Canton	Ohio
United States	Waverly Hematology Oncology	Cary	North Carolina
United States	The Christ Hospital Cancer Center	Cincinnati	Ohio
United States	John B. Amos Cancer Center	Columbus	Georgia
United States	Pontchartrain Cancer Center	Covington	Louisiana
United States	Commonwealth Hematology-Oncology, PSC	Danville	Kentucky
United States	Denver Health & Hospital Authority	Denver	Colorado
United States	Cancer Center of Middle Georgia	Dublin	Georgia
United States	Providence Regional Center Partnership	Everett	Washington
United States	Dwight D. Eisenhower Army Medical Center	Fort Gordon	Georgia
United States	Compassionate Care Research Group, Inc.	Fountain Valley	California
United States	California Cancer Associates for Research and Excellence Inc.	Fresno	California
United States	Gaston Hematology & Oncology Associates, PC	Gastonia	North Carolina
United States	The West Clinic, PC, d/b/a West Cancer Center	Germantown	Tennessee
United States	CHI Health St Francis, St Francis Cancer Treatment Center	Grand Island	Nebraska
United States	Hattiesburg Clinic Hematology/Oncology	Hattiesburg	Mississippi
United States	Pasco Pinellas Cancer Center	Holiday	Florida
United States	Genesis Cancer Center	Hot Springs	Arkansas
United States	FPN Oncology and Hematology Specialists	Indianapolis	Indiana
United States	NEA Baptist Clinic | Fowler Family Center for Cancer Care	Jonesboro	Arkansas
United States	Freeman Health Systems	Joplin	Missouri
United States	Envision Cancer Center, LLC	Laredo	Texas
United States	Pacific Shores Medical Group	Long Beach	California
United States	Los Angeles Hematology Oncology Medical Group	Los Angeles	California
United States	Texas Oncology, PA- McAllen South 2nd Street	McAllen	Texas
United States	Lakes Research, LLC	Miami Lakes	Florida
United States	West Virginia University	Morgantown	West Virginia
United States	Mid-Florida Hematology and Oncology Centers	Orange City	Florida
United States	Desert Regional Medical Center	Palm Springs	California
United States	Oncology Specialists, SC	Park Ridge	Illinois
United States	Millennium Oncology	Pembroke Pines	Florida
United States	BRCR Medical Center Inc	Plantation	Florida
United States	Delta Hematology/Oncology Associates	Portsmouth	Virginia
United States	Emad Ibrahim, MD, INC.	Redlands	California
United States	Carolina Blood and Cancer Care Associates	Rock Hill	South Carolina
United States	Quest Research Institute	Royal Oak	Michigan
United States	Coborn Cancer Center	Saint Cloud	Minnesota
United States	Pinellas Hematology and Oncology	Saint Petersburg	Florida
United States	Northwest Medical Specialties, PLLC	Tacoma	Washington
United States	ACRC/ Arizona Clinical Research Center Inc.	Tucson	Arizona
United States	HOPE Cancer Center of East Texas	Tyler	Texas
United States	Innovative Clinical Research Institute/ The Oncology Institute of Hope and Innovation	Whittier	California
United States	Bond & Steele Clinic, PA.	Winter Haven	Florida
United States	St. Elizabeth Youngstown Hospital JACBCC/Oncology/ Mercy Health Youngstown LLC	Youngstown	Ohio
United States	Yuma Regional Cancer Center	Yuma	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Spectrum Pharmaceuticals, Inc

Countries where clinical trial is conducted

United States,  Canada,  Hungary,  India,  Korea, Republic of,  Poland, 

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 per liter [L]) from the first occurrence of ANC below the threshold.	Day 1 and daily on Days 4-15 in Cycle 1 (each cycle = 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 the participants ANC increased to >=1.5×10^9/L after the expected nadir. For participants with ANC value >=1.5×10^9/L at all times, time to ANC Recovery was assigned a value of 0.	Day 1 and daily on Days 4-15 in Cycle 1 (each cycle = 21 days)
Secondary	Depth of ANC Nadir in Cycle 1	The 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 daily on Days 4-15 in Cycle 1 (each cycle = 21 days)
Secondary	Number of Participants With Febrile Neutropenia (FN) in Cycle 1	FN was defined as an oral temperature >38.3 degree Celsius (°C) (101.0 degrees Fahrenheit [°F]) or two consecutive readings of >38.0°C (100.4°F) for 2 hours and ANC <1.0×10^9/L.	Day 1 and daily on Days 4-15 in Cycle 1 (each cycle = 21 days)
Secondary	Duration of Severe Neutropenia (DSN) in Cycles 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 ANC below the threshold.	Days 1, 4, 7, 10, and 15 of Cycles 2, 3, and 4 (each cycle = 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 daily on Days 4-15 in Cycle 1 (each cycle = 21 days)
Secondary	Number of Participants With Febrile Neutropenia in Cycles 2, 3 and 4	FN was defined as an oral temperature >38.3°C (101.0°F) or two consecutive readings of >38.0°C (100.4°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 = 21 days)
Secondary	Relative Dose Intensity (RDI) of TC Chemotherapy	RDI was defined as the percentage of the planned dose of TC chemotherapy that each participant actually received during the study, and is expressed as the total dose received, divided by total dose planned 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, 2, 3 and 4 (each cycle = 21 days)
Secondary	Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs), and Death	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 is any AE that occurred from the first dose of study treatment through 12 months after the last dose of study treatment or 35 (±5) days after date of participant early discontinuation. 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.	Up to 4 cycles (each cycle = 21 days) plus a 12-month follow-up from the last dose (up to 15 months)
Secondary	Number of Participants With Clinically Significant Laboratory Abnormalities	The number of participants with clinically significant hematology (including basophils, basophils/leukocytes, eosinophils, eosinophils/leukocytes, hematocrit, hemoglobin, lymphocytes, lymphocytes/leukocytes, monocytes, monocytes/leukocytes, neutrophils, neutrophils/leukocytes, platelets, and white blood cells) and serum chemistry (including alanine aminotransferase [ALT], alkaline phosphatase [ALP], aspartate aminotransferase [AST], bilirubin, calcium, cholesterol, creatinine, potassium, sodium, and triglycerides) laboratory abnormalities were reported. Clinically significant findings in laboratory parameters were based on investigator's discretion according to Common Technical Criteria for Adverse Events (CTCAE) Version 4.03.	Up to 4 cycles (each cycle = 21 days) plus a 12-month follow-up from the last dose (up to 15 months)