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

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)

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).

Study Overview

• Status: Completed
• Conditions: Breast Cancer; Neutropenia
• Intervention / Treatment: Drug: SPI-2012; Drug: Docetaxel; Drug: Cyclophosphamide; Drug: Pegfilgrastim

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.

• Study Type: Interventional
• Enrollment (Actual): 237
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Longueuil, Quebec, Canada, J4V 2H1
      • CISSS de la Monteregie-Centre
    • Montreal, Quebec, Canada, H3T 1E2
      • Jewish General Hospital
• Hungary
  • Budapest, Hungary, 1062
    • Magyar Honvedseg Egeszsegugyi Kozpont, Onkologiai Osztaly
  • Budapest, Hungary, 1115
    • Szent Imre Egyetemi Oktatokorhaz, Klinikai Onkologiai Osztaly
  • Budapest, Hungary, 1122
    • Orszagos Onkologiai Intezet, ""B"" Belgyogyaszati Onkologiai Osztaly
  • Miskolc, Hungary, 3526
    • Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi Okato Korhaz, Klinikai Onkologiai es Sugarterapias Centrum
  • Nyíregyháza, Hungary, 4400
    • Szabolcs-Szatmar-Bereg Megyei Korhazak, Egyetemi Oktato Korhaz, Onkoradiologiai Osztaly
  • Szekszard, Hungary, 7100
    • Tolna Megyei Balassa Janos Korhaz, Klinikai Onkologiai Osztaly
• India
  • Maharashtra
    • Pune, Maharashtra, India, 411011
      • KEM Hospital Research Centre
  • Tamil Nadu
    • Vellore, Tamil Nadu, India, 632004
      • Christian Medical College
• Korea, Republic of
  • Gangnam-gu Seoul
    • Irwon-ro, Gangnam-gu Seoul, Korea, Republic of, 06351
      • Samsung Medical Center
  • Gangwon-do
    • Ilsan-ro, Gangwon-do, Korea, Republic of, 26426
      • Wonju Severance Christian Hospital
  • Gyeonggi-do
    • IIsan-ro, Gyeonggi-do, Korea, Republic of, 10408
      • National Cancer Center
    • Yatap-ro, Gyeonggi-do, Korea, Republic of, 13496
      • CHA Bundang Medical Center
  • Jongno-gu Seoul
    • Daehwa-ro, Jongno-gu Seoul, Korea, Republic of, 03080
      • Seoul National University Hospital
  • Jung-guIncheon
    • Inhang-ro, Jung-guIncheon, Korea, Republic of, 22332
      • Inha University Hospital
  • Seongbuk-guSeoul
    • Inchon-ro, Seongbuk-guSeoul, Korea, Republic of, 02841
      • Korea University Anam Hospital
  • Seoul
    • Yonsei-ro, Seoul, Korea, Republic of, 03722
      • Severance Hospital
• Poland
  • Bialystok, Poland, 15-027
    • BIALOSTOCKIE CENTRUM ONKOLOGII im. Marii Sklodowskiej-Curie Oddzial Onkologii Klinicznej im. Ewy Pileckiej z Pododdzialem Chemioterapii dziennej
  • Grudziadz, Poland, 86-300
    • Regionalny Szpital Specjalistyczny im. dr Wladyslawa Bieganskiego Oddział Onkologii Klinicznej
  • Lodz, Poland, 93-338
    • Instytut Centrum Zdrowia Matki Polki Klinika Chirurgii Onkologicznej i Chorob Piersi z Pododdzialem Onkologii Klinicznej
  • Poznan, Poland, 60-569
    • Pracownia Leku Cytotoksycznego Szpitala Klinicznego Przemienienia Panskiego UM im. Karola Marcinkowskiego w Poznaniu
  • Racibórz, Poland, 47-400
    • Szpital Rejonowy im. Dr. Jozefa Rostka w Raciborzu Dzienny Oddzial Chemioterapii
  • Rzeszow, Poland, 35-021
    • Mrukmed. Lekarz Beata Madej Mruk i Partner. Spólka Partnerska Oddzial nr 1 w Rzeszowie
  • Szczecin, Poland, 71-730
    • Zachodniopomorskie Centrum Onkologii Osrodek Innowacyjnosci, Rozwoju i Badan Klinicznych
• United States
  • Arizona
    • Tucson, Arizona, United States, 85715
      • ACRC/ Arizona Clinical Research Center Inc.
    • Yuma, Arizona, United States, 85364
      • Yuma Regional Cancer Center
  • Arkansas
    • Hot Springs, Arkansas, United States, 71913
      • Genesis Cancer Center
    • Jonesboro, Arkansas, United States, 72401
      • NEA Baptist Clinic | Fowler Family Center for Cancer Care
  • California
    • Anaheim, California, United States, 92801
      • Pacific Cancer Medical Center, Inc.
    • Fountain Valley, California, United States, 92708
      • Compassionate Care Research Group, Inc.
    • Fresno, California, United States, 93720
      • California Cancer Associates for Research and Excellence Inc.
    • Long Beach, California, United States, 90813
      • Pacific Shores Medical Group
    • Los Angeles, California, United States, 90017
      • Los Angeles Hematology Oncology Medical Group
    • Palm Springs, California, United States, 92262
      • Desert Regional Medical Center
    • Redlands, California, United States, 92373
      • Emad Ibrahim, MD, Inc.
    • Whittier, California, United States, 90603
      • Innovative Clinical Research Institute/ The Oncology Institute of Hope and Innovation
  • Colorado
    • Denver, Colorado, United States, 80204
      • Denver Health & Hospital Authority
  • Florida
    • Holiday, Florida, United States, 34691
      • Pasco Pinellas Cancer Center
    • Miami Lakes, Florida, United States, 33014
      • Lakes Research, LLC
    • Orange City, Florida, United States, 32763
      • Mid-Florida Hematology and Oncology Centers
    • Pembroke Pines, Florida, United States, 33024
      • Millennium Oncology
    • Plantation, Florida, United States, 33324
      • BRCR Medical Center Inc
    • Saint Petersburg, Florida, United States, 33709
      • Pinellas Hematology and Oncology
    • Winter Haven, Florida, United States, 33880
      • Bond & Steele Clinic, PA.
  • Georgia
    • Columbus, Georgia, United States, 31904
      • John B. Amos Cancer Center
    • Dublin, Georgia, United States, 31021
      • Cancer Center of Middle Georgia
    • Fort Gordon, Georgia, United States, 30905
      • Dwight D. Eisenhower Army Medical Center
  • Idaho
    • Boise, Idaho, United States, 83706
      • Saint Alphonsus Regional Medical Center
  • Illinois
    • Park Ridge, Illinois, United States, 60068
      • Oncology Specialists, SC
  • Indiana
    • Indianapolis, Indiana, United States, 46237
      • FPN Oncology and Hematology Specialists
  • Kentucky
    • Danville, Kentucky, United States, 40422
      • Commonwealth Hematology-Oncology, PSC
  • Louisiana
    • Covington, Louisiana, United States, 70433
      • Pontchartrain Cancer Center
  • Michigan
    • Royal Oak, Michigan, United States, 48073
      • Quest Research Institute
  • Minnesota
    • Saint Cloud, Minnesota, United States, 56303
      • Coborn Cancer Center
  • Mississippi
    • Hattiesburg, Mississippi, United States, 39401
      • Hattiesburg Clinic Hematology/Oncology
  • Missouri
    • Joplin, Missouri, United States, 64804
      • Freeman Health Systems
  • Montana
    • Billings, Montana, United States, 59102
      • St. Vincent Frontier Cancer Center
  • Nebraska
    • Grand Island, Nebraska, United States, 68803
      • CHI Health St Francis, St Francis Cancer Treatment Center
  • North Carolina
    • Cary, North Carolina, United States, 27518
      • Waverly Hematology Oncology
    • Gastonia, North Carolina, United States, 28054
      • Gaston Hematology & Oncology Associates, PC
  • Ohio
    • Canton, Ohio, United States, 44710
      • Aultman Hospital
    • Cincinnati, Ohio, United States, 45219
      • The Christ Hospital Cancer Center
    • Youngstown, Ohio, United States, 44501
      • St. Elizabeth Youngstown Hospital JACBCC/Oncology/ Mercy Health Youngstown LLC
  • South Carolina
    • Rock Hill, South Carolina, United States, 29732
      • Carolina Blood and Cancer Care Associates
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • The West Clinic, PC, d/b/a West Cancer Center
  • Texas
    • Bryan, Texas, United States, 77802
      • CHI St Joseph Health Cancer Center
    • Laredo, Texas, United States, 78041
      • Envision Cancer Center, LLC
    • McAllen, Texas, United States, 78503
      • Texas Oncology, PA- McAllen South 2nd Street
    • Tyler, Texas, United States, 75701
      • HOPE Cancer Center of East Texas
  • Virginia
    • Portsmouth, Virginia, United States, 23704
      • Delta Hematology/Oncology Associates
  • Washington
    • Everett, Washington, United States, 98201
      • Providence Regional Center Partnership
    • Tacoma, Washington, United States, 98405
      • Northwest Medical Specialties, PLLC
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: (Arm 1): SPI-2012 and TC; 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.	Drug: SPI-2012; Supplied in prefilled single-use syringes for subcutaneous injection, administered on Day 2 of each cycle; Other Names: Rolontis®; Eflapegrastim; HM10460A; Drug: Docetaxel; 75mg/m^2 IV infusion administered on Day 1 of each cycle; Other Names: Taxotere; Drug: Cyclophosphamide; 600mg/m^2 IV infusion administered on Day 1 of each cycle; Other Names: Cytoxan
Experimental: (Arm 2): Pegfilgrastim and TC; 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.	Drug: Docetaxel; 75mg/m^2 IV infusion administered on Day 1 of each cycle; Other Names: Taxotere; Drug: Cyclophosphamide; 600mg/m^2 IV infusion administered on Day 1 of each cycle; Other Names: Cytoxan; Drug: Pegfilgrastim; Subcutaneous injection administered on Day 2 of each cycle.; Other Names: Neulasta®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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)
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)
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)
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)
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)
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)
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)
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)

Collaborators and Investigators

• Sponsor: Spectrum Pharmaceuticals, Inc

Study record dates

Study Major Dates

• Study Start (Actual): May 10, 2017
• Primary Completion (Actual): June 8, 2018
• Study Completion (Actual): May 6, 2019

Study Registration Dates

• First Submitted: October 27, 2016
• First Submitted That Met QC Criteria: November 1, 2016
• First Posted (Estimate): November 2, 2016

Study Record Updates

• Last Update Posted (Actual): March 2, 2022
• Last Update Submitted That Met QC Criteria: February 28, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: Breast Cancer; Early Stage Breast Cancer; Neutropenia; Docetaxel + Cyclophosphamide (TC) chemotherapy; Long-acting Granulocyte Colony Stimulating Factor
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Hematologic Diseases; Breast Diseases; Agranulocytosis; Leukopenia; Leukocyte Disorders; Breast Neoplasms; Neutropenia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Docetaxel; Cyclophosphamide
• Other Study ID Numbers: SPI-GCF-302; 2016-003469-24 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No