SPI-2012 vs Pegfilgrastim in Management of Neutropenia in Breast Cancer Participants With Docetaxel and Cyclophosphamide
- Conditions
- NeutropeniaBreast Cancer
- Interventions
- Registration Number
- NCT02953340
- Lead Sponsor
- Spectrum Pharmaceuticals, Inc
- Brief 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).
- Detailed 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 & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 237
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description (Arm 1): SPI-2012 and TC SPI-2012 At each cycle for 4 cycles, participants received SPI-2012 at a fixed dose of 13.2 milligrams (mg)/0.6 milliliter (mL), \[3.6 mg granulocyte colony-stimulating factor {G-CSF}\] subcutaneously (SC) approximately 24-26 hours after receiving intravenous (IV) infusion of docetaxel 75 mg/m\^2 and cyclophosphamide 600 mg/m\^2 IV infusion per institute's standard of care. All participants were followed for 35 (±5) days after last study treatment or patient discontinuation and long-term safety follow-up continued for 12 months after last dose of study treatment. (Arm 1): SPI-2012 and TC Docetaxel At each cycle for 4 cycles, participants received SPI-2012 at a fixed dose of 13.2 milligrams (mg)/0.6 milliliter (mL), \[3.6 mg granulocyte colony-stimulating factor {G-CSF}\] subcutaneously (SC) approximately 24-26 hours after receiving intravenous (IV) infusion of docetaxel 75 mg/m\^2 and cyclophosphamide 600 mg/m\^2 IV infusion per institute's standard of care. All participants were followed for 35 (±5) days after last study treatment or patient discontinuation and long-term safety follow-up continued for 12 months after last dose of study treatment. (Arm 2): Pegfilgrastim and TC Cyclophosphamide At each cycle for 4 cycles, participants received pegfilgrastim 6 mg (6 mg/0.6 mL GCSF) SC approximately 24-26 hours after receiving IV infusion of docetaxel 75 mg/m\^2 and cyclophosphamide 600 mg/m\^2 IV infusion per institute's standard of care. All participants were followed for 35 (±5) days after last study treatment or patient discontinuation and long-term safety follow-up continued for 12 months after last dose of study treatment. (Arm 1): SPI-2012 and TC Cyclophosphamide At each cycle for 4 cycles, participants received SPI-2012 at a fixed dose of 13.2 milligrams (mg)/0.6 milliliter (mL), \[3.6 mg granulocyte colony-stimulating factor {G-CSF}\] subcutaneously (SC) approximately 24-26 hours after receiving intravenous (IV) infusion of docetaxel 75 mg/m\^2 and cyclophosphamide 600 mg/m\^2 IV infusion per institute's standard of care. All participants were followed for 35 (±5) days after last study treatment or patient discontinuation and long-term safety follow-up continued for 12 months after last dose of study treatment. (Arm 2): Pegfilgrastim and TC Pegfilgrastim At each cycle for 4 cycles, participants received pegfilgrastim 6 mg (6 mg/0.6 mL GCSF) SC approximately 24-26 hours after receiving IV infusion of docetaxel 75 mg/m\^2 and cyclophosphamide 600 mg/m\^2 IV infusion per institute's standard of care. All participants were followed for 35 (±5) days after last study treatment or patient discontinuation and long-term safety follow-up continued for 12 months after last dose of study treatment. (Arm 2): Pegfilgrastim and TC Docetaxel At each cycle for 4 cycles, participants received pegfilgrastim 6 mg (6 mg/0.6 mL GCSF) SC approximately 24-26 hours after receiving IV infusion of docetaxel 75 mg/m\^2 and cyclophosphamide 600 mg/m\^2 IV infusion per institute's standard of care. All participants were followed for 35 (±5) days after last study treatment or patient discontinuation and long-term safety follow-up continued for 12 months after last dose of study treatment.
- Primary Outcome Measures
Name Time Method Duration of Severe Neutropenia (DSN) in Cycle 1 Day 1 and daily on Days 4-15 in Cycle 1 (each cycle = 21 days) 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.
- Secondary Outcome Measures
Name Time Method Time to Absolute Neutrophil Count (ANC) Recovery in Cycle 1 Day 1 and daily on Days 4-15 in Cycle 1 (each cycle = 21 days) 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.
Duration of Severe Neutropenia (DSN) in Cycles 2, 3 and 4 Days 1, 4, 7, 10, and 15 of Cycles 2, 3, and 4 (each cycle = 21 days) 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.
Number of Participants With Febrile Neutropenia (FN) in Cycle 1 Day 1 and daily on Days 4-15 in Cycle 1 (each cycle = 21 days) 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.
Number of Participants With Neutropenic Complications in Cycle 1 Day 1 and daily on Days 4-15 in Cycle 1 (each cycle = 21 days) Neutropenic complications refer to hospitalizations due to neutropenic events and/or the use of anti-infectives due to neutropenia.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs), and Death Up to 4 cycles (each cycle = 21 days) plus a 12-month follow-up from the last dose (up to 15 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 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.
Depth of ANC Nadir in Cycle 1 Day 1 and daily on Days 4-15 in Cycle 1 (each cycle = 21 days) The depth of ANC Nadir was defined as the lowest ANC value after administration of study drug (SPI-2012 or pegfilgrastim) in Cycle 1.
Relative Dose Intensity (RDI) of TC Chemotherapy Cycles 1, 2, 3 and 4 (each cycle = 21 days) 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.
Number of Participants With Clinically Significant Laboratory Abnormalities Up to 4 cycles (each cycle = 21 days) plus a 12-month follow-up from the last dose (up to 15 months) 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.
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 = 21 days) 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.
Trial Locations
- Locations (74)
Millennium Oncology
🇺🇸Pembroke Pines, Florida, United States
Hattiesburg Clinic Hematology/Oncology
🇺🇸Hattiesburg, Mississippi, United States
Lakes Research, LLC
🇺🇸Miami Lakes, Florida, United States
Freeman Health Systems
🇺🇸Joplin, Missouri, United States
Quest Research Institute
🇺🇸Royal Oak, Michigan, United States
Coborn Cancer Center
🇺🇸Saint Cloud, Minnesota, United States
CISSS de la Montérégie-Centre
🇨🇦Longueuil, Quebec, Canada
St. Elizabeth Youngstown Hospital JACBCC/Oncology/ Mercy Health Youngstown LLC
🇺🇸Youngstown, Ohio, United States
ACRC/ Arizona Clinical Research Center Inc.
🇺🇸Tucson, Arizona, United States
Genesis Cancer Center
🇺🇸Hot Springs, Arkansas, United States
NEA Baptist Clinic | Fowler Family Center for Cancer Care
🇺🇸Jonesboro, Arkansas, United States
St. Vincent Frontier Cancer Center
🇺🇸Billings, Montana, United States
Pracownia Leku Cytotoksycznego Szpitala Klinicznego Przemienienia Panskiego UM im. Karola Marcinkowskiego w Poznaniu
🇵🇱Poznan, Poland
MrukMed. Lekarz Beata Madej Mruk i Partner. Spolka Partnerska Oddzial nr 1 w Rzeszowie
🇵🇱Rzeszow, Poland
Innovative Clinical Research Institute/ The Oncology Institute of Hope and Innovation
🇺🇸Whittier, California, United States
Oncology Specialists, SC
🇺🇸Park Ridge, Illinois, United States
CHI Health St Francis, St Francis Cancer Treatment Center
🇺🇸Grand Island, Nebraska, United States
Magyar Honvedseg Egeszsegugyi Kozpont, Onkologiai Osztaly
🇭🇺Budapest, Hungary
Szent Imre Egyetemi Oktatokorhaz, Klinikai Onkologiai Osztaly
🇭🇺Budapest, Hungary
National Cancer Center
🇰🇷IIsan-ro, Gyeonggi-do, Korea, Republic of
Wonju Severance Christian Hospital
🇰🇷Ilsan-ro, Gangwon-do, Korea, Republic of
The Christ Hospital Cancer Center
🇺🇸Cincinnati, Ohio, United States
Christian Medical College
🇮🇳Vellore, Tamil Nadu, India
Yuma Regional Cancer Center
🇺🇸Yuma, Arizona, United States
Compassionate Care Research Group, Inc.
🇺🇸Fountain Valley, California, United States
California Cancer Associates for Research and Excellence Inc.
🇺🇸Fresno, California, United States
Pacific Shores Medical Group
🇺🇸Long Beach, California, United States
Pacific Cancer Medical Center, Inc.
🇺🇸Anaheim, California, United States
Los Angeles Hematology Oncology Medical Group
🇺🇸Los Angeles, California, United States
Desert Regional Medical Center
🇺🇸Palm Springs, California, United States
Pasco Pinellas Cancer Center
🇺🇸Holiday, Florida, United States
Emad Ibrahim, MD, INC.
🇺🇸Redlands, California, United States
Mid-Florida Hematology and Oncology Centers
🇺🇸Orange City, Florida, United States
BRCR Medical Center Inc
🇺🇸Plantation, Florida, United States
Pinellas Hematology and Oncology
🇺🇸Saint Petersburg, Florida, United States
Bond & Steele Clinic, PA.
🇺🇸Winter Haven, Florida, United States
John B. Amos Cancer Center
🇺🇸Columbus, Georgia, United States
Saint Alphonsus Regional Medical Center
🇺🇸Boise, Idaho, United States
Cancer Center of Middle Georgia
🇺🇸Dublin, Georgia, United States
Dwight D. Eisenhower Army Medical Center
🇺🇸Fort Gordon, Georgia, United States
FPN Oncology and Hematology Specialists
🇺🇸Indianapolis, Indiana, United States
Commonwealth Hematology-Oncology, PSC
🇺🇸Danville, Kentucky, United States
Pontchartrain Cancer Center
🇺🇸Covington, Louisiana, United States
Waverly Hematology Oncology
🇺🇸Cary, North Carolina, United States
Gaston Hematology & Oncology Associates, PC
🇺🇸Gastonia, North Carolina, United States
Aultman Hospital
🇺🇸Canton, Ohio, United States
Carolina Blood and Cancer Care Associates
🇺🇸Rock Hill, South Carolina, United States
The West Clinic, PC, d/b/a West Cancer Center
🇺🇸Germantown, Tennessee, United States
Texas Oncology, PA- McAllen South 2nd Street
🇺🇸McAllen, Texas, United States
HOPE Cancer Center of East Texas
🇺🇸Tyler, Texas, United States
CHI St Joseph Health Cancer Center
🇺🇸Bryan, Texas, United States
Envision Cancer Center, LLC
🇺🇸Laredo, Texas, United States
Providence Regional Center Partnership
🇺🇸Everett, Washington, United States
Delta Hematology/Oncology Associates
🇺🇸Portsmouth, Virginia, United States
Northwest Medical Specialties, PLLC
🇺🇸Tacoma, Washington, United States
Jewish General Hospital
🇨🇦Montreal, Quebec, Canada
Tolna Megyei Balassa Janos Korhaz, Klinikai Onkologiai Osztaly
🇭🇺Szekszard, Hungary
Orszagos Onkologiai Intezet, ""B"" Belgyogyaszati 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
KEM Hospital Research Centre
🇮🇳Pune, Maharashtra, India
Samsung Medical Center
🇰🇷Irwon-ro, Gangnam-gu Seoul, Korea, Republic of
Regionalny Szpital Specjalistyczny im. dr Wladyslawa Bieganskiego Oddział Onkologii Klinicznej
🇵🇱Grudziadz, Poland
Cha Bundang Medical Center
🇰🇷Yatap-ro, Gyeonggi-do, Korea, Republic of
Korea University Anam Hospital
🇰🇷Inchon-ro, Seongbuk-guSeoul, Korea, Republic of
BIALOSTOCKIE CENTRUM ONKOLOGII im. Marii Sklodowskiej-Curie Oddzial Onkologii Klinicznej im. Ewy Pileckiej z Pododdzialem Chemioterapii dziennej
🇵🇱Bialystok, Poland
Inha University Hospital
🇰🇷Inhang-ro, Jung-guIncheon, Korea, Republic of
Seoul National University Hospital
🇰🇷Daehwa-ro, Jongno-gu Seoul, Korea, Republic of
Severance Hospital
🇰🇷Yonsei-ro, Seoul, Korea, Republic of
Instytut Centrum Zdrowia Matki Polki Klinika Chirurgii Onkologicznej i Chorob Piersi z Pododdzialem Onkologii Klinicznej
🇵🇱Lodz, Poland
Zachodniopomorskie Centrum Onkologii Osrodek Innowacyjnosci, Rozwoju i Badan Klinicznych
🇵🇱Szczecin, Poland
Szpital Rejonowy im. Dr. Jozefa Rostka w Raciborzu Dzienny Oddzial Chemioterapii
🇵🇱Racibórz, Poland
West Virginia University
🇺🇸Morgantown, West Virginia, United States
Denver Health & Hospital Authority
🇺🇸Denver, Colorado, United States