Phase 2 Study of SPI-2012 or Pegfilgrastim for the Management of Neutropenia in Participants With Breast Cancer

Neutropenia Clinical Trial

Official title:

Phase 2, Open-Label, Dose-Ranging Study of SPI-2012 (HM10460A) or Pegfilgrastim Use for the Management of Neutropenia in Patients With Breast Cancer Who Are Candidates for Adjuvant and Neoadjuvant Chemotherapy With the Docetaxel + Cyclophosphamide (TC) Regimen

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01724866
• Other study ID #: SPI-GCF-12-201
• Secondary ID: 2013-003094-10
• Status: Completed
• Phase: Phase 2
• Start date: March 25, 2013
• Est. completion date: August 12, 2014

Study information

• Verified date: March 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 assess the effect of test doses of SPI-2012 on the duration of severe neutropenia (DSN) during Cycle 1 in participants with breast cancer who are candidates for adjuvant or neoadjuvant chemotherapy.

Description:

This is an open label, multicenter, dose ranging study, sequentially enrolled by study dose, with a non-inferiority design to compare the effectiveness of SPI-2012 relative to a fixed dose of pegfilgrastim as a concurrent active control to each dose of SPI-2012 in participants with breast cancer. This study included four arms comprising three dose levels of SPI-2012 (Arm 1: 45 µg/kg, Arm 2: 135 µg/kg, Arm 3: 270 µg/kg) versus pegfilgrastim (Arm 4: 6 mg). The start of study is defined as the initiation of treatment with SPI-2012 or pegfilgrastim. The duration of treatment consists of a maximum of 4 cycles (21 days per cycle) beginning on Day 1 with chemotherapy administration and continue through Day 21, plus a 30-day follow-up period, unless any of the discontinuation criteria applies. The target population are participants with breast cancer who are candidates for neoadjuvant or adjuvant treatment with Docetaxel + Cyclophosphamide (TC) chemotherapy. All participants who receive at least 1 dose of either SPI-2012 or pegfilgrastim were followed for safety through 30 days after their last dose of study treatment or until all treatment-related adverse events (AEs) have resolved or returned to baseline/Grade 1, whichever is longer, or until it is determined that the outcome will not change with further follow-up.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 148
• Est. completion date: August 12, 2014
• Est. primary completion date: August 12, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically confirmed breast cancer and candidate for adjuvant or neoadjuvant chemotherapy
• Candidate for docetaxel and cyclophosphamide chemotherapy
• Female or male at least 18 years of age
• Eastern Cooperative Oncology Group (ECOG) = 2
• Absolute neutrophil count (ANC) = 1.5×109/L
• Platelet count = 100 x 10^9/L
• Creatinine = 1.5 x upper limit of normal (ULN)
• Total bilirubin =1.5 mg/dL(= 25.65 µmol/L).
• Aspartate aminotransferase per serum glutamic-oxaloacetic transaminase (AST/SGOT) and/or alanine aminotransferase per serum glutamic-pyruvic transaminase (ALT/SGPT) = 2.5 x ULN
• Hemoglobin > 9 g/dL
• Alkaline phosphatase = 1.5 x ULN

Exclusion Criteria:

• Known sensitivity to E. coli-derived products or known sensitivity to any of the products to be administered
• Known Human Immunodeficiency Virus (HIV) infection
• Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) diagnosis with detectable viral load or immunological evidence of chronic active disease
• Active infection or any serious underlying medical condition that would impair ability to receive protocol treatment
• Prior bone marrow or stem cell transplant
• Prolonged exposure to glucocorticosteroids and immunosuppressive agents

Related Conditions & MeSH terms

• Neutropenia

Intervention

Drug:
• SPI-2012
SPI-2012 SC injection.
• Pegfilgrastim
Pegfilgrastim SC injection, per manufacturer's Prescribing Information.
• Docetaxel
Docetaxel given based on standard dose for chemotherapy.
• Cyclophosphamide
Cyclophosphamide given based on standard dose for chemotherapy.

Locations

Country	Name	City	State
Australia	Royal Hobart	Brisbane
Australia	Frankston Hospital	Frankston	Victoria
Australia	Ashford Cancer Center Research	Kurralta Park
Australia	Breast Cancer Research Center, WA	Perth
Australia	Ballarat Oncology & Haematology	Wendouree
Georgia	LTD " Cancer Center of Adjara Autonomic Republic"	Batumi
Georgia	Ltd ' Medulla - Chemotherapy and Immunotherapy Clinic	Tbilisi
Hungary	National Institute of Oncology	Budapest
Hungary	State Health Center	Budapest
Hungary	Uzsoki Hospital	Budapest
Hungary	University Debrecen, Oncology Clinic	Debrecen
Hungary	Szabolcs - Szatmár - Bereg megyei Kórházak és Egyetemi Oktatókórház	Nyíregyháza
Israel	Ziv Medical Center	Zefat
Poland	Regionalny Szpital Specjalistyczny	Grudziadz
Poland	Szpital Uniwersytecki w Krakowie	Kraków
Poland	Dzienny Oddzial Chemioterapii	Racibórz
Poland	MTZ Clinical Research Sp. z o.o.	Warszawa
United States	New York Oncology Hematology, PC	Albany	New York
United States	Good Samaritan Hospital, Corvallis	Corvallis	Oregon
United States	California Cancer Associates for Research and Excellence	Fresno	California
United States	Arizona Center for Cancer Care	Glendale	Arizona
United States	Kentucky Cancer Clinic	Hazard	Kentucky
United States	Beaver Medical Group	Highland	California
United States	California Cancer Associates for Research and Excellence	Los Angeles	California
United States	Desert Springs Cancer Care	Scottsdale	Arizona
United States	North Shore Hematology/Oncology Associates	Setauket	New York
United States	Innovative Clinical Research Institute	Whittier	California

Sponsors (1)

Lead Sponsor	Collaborator
Spectrum Pharmaceuticals, Inc

Countries where clinical trial is conducted

United States,  Australia,  Georgia,  Hungary,  Israel,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Duration of Severe Neutropenia (DSN) in Cycle 1	DSN was defined as the interval from the day of first observation of severe neutropenia (ANC <0.5*10^9/L, Grade 4 neutropenia per NCI CTCAE) to the first ANC recovery to => 2.0*10^9/L in Cycle 1.	Cycle 1 (each cycle was 21 days)
Secondary	Duration of DSN in Cycle 2	DSN was defined as the interval from the day of first observation of severe neutropenia (ANC <0.5*10^9/L, Grade 4 neutropenia per NCI CTCAE) to the first ANC recovery to => 2.0*10^9/L in Cycle 2.	Cycle 2 (each cycle was 21 days)
Secondary	Duration of DSN in Cycle 3	DSN was defined as the interval from the day of first observation of severe neutropenia (ANC <0.5*10^9/L, Grade 4 neutropenia per NCI CTCAE) to the first ANC recovery to => 2.0*10^9/L in Cycle 3.	Cycle 3 (each cycle was 21 days)
Secondary	Duration of DSN in Cycle 4	DSN was defined as the interval from the day of first observation of severe neutropenia (ANC <0.5*10^9/L, Grade 4 neutropenia per NCI CTCAE) to the first ANC recovery to => 2.0*10^9/L in Cycle 4.	Cycle 4 (each cycle was 21 days)
Secondary	Time to ANC Recovery in Cycle 1	Time to ANC recovery was defined as the time from chemotherapy administration until ANC increased to = 2×10^9/L after the expected nadir within Cycle 1. Time to ANC recovery was not calculated for participants whose ANC value didn't drop below 2 x10^9/L within Cycle 1.	Cycle 1 (each cycle was 21 days)
Secondary	Time to ANC Recovery in Cycle 2	Time to ANC recovery was defined as the time from chemotherapy administration until ANC increased to =2×10^9/L after the expected nadir within Cycle 2. Time to ANC recovery was not calculated for participants whose ANC value didn't drop below 2 x10^9/L within Cycle 2.	Cycle 2 (each cycle was 21 days)
Secondary	Time to ANC Recovery in Cycle 3	Time to ANC recovery was defined as the time from chemotherapy administration until ANC increased to =2×10^9/L after the expected nadir within Cycle 3. Time to ANC recovery was not calculated for participants whose ANC value didn't drop below 2 x10^9/L within Cycle 3.	Cycle 3 (each cycle was 21 days)
Secondary	Time to ANC Recovery in Cycle 4	Time to ANC recovery was defined as the time from chemotherapy administration until ANC increased to =2×10^9/L after the expected nadir within Cycle 4. Time to ANC recovery was not calculated for participants whose ANC value didn't drop below 2 x10^9/L within Cycle 4.	Cycle 4 (each cycle was 21 days)
Secondary	Absolute Neutrophil Count (ANC) Nadir Overtime in Cycle 1	Mean ANC nadir was defined as the mean of the lowest ANC value (*10^9/L) after administration of the study drug (SPI-2012 or pegfilgrastim) on any day in Days 1-3 of Cycle 1.	Cycle 1 (each cycle was 21 days)
Secondary	Absolute ANC Nadir Overtime in Cycle 2	Mean ANC nadir was defined as the mean of the lowest ANC value (*10^9/L) after administration of the study drug (SPI-2012 or pegfilgrastim) on any day in Days 1-3 of Cycle 2.	Cycle 2 (each cycle was 21 days)
Secondary	Absolute ANC Nadir Overtime in Cycle 3	Mean ANC nadir was defined as the mean of the lowest ANC value (*10^9/L) after administration of the study drug (SPI-2012 or pegfilgrastim) on any day in Days 1-3 of Cycle 3.	Cycle 3 (each cycle was 21 days)
Secondary	Absolute ANC Nadir Overtime in Cycle 4	Mean ANC nadir was defined as the mean of the lowest ANC value (*10^9/L) after administration of the study drug (SPI-2012 or pegfilgrastim) on any day in Days 1-3 of Cycle 4.	Cycle 4 (each cycle was 21 days)
Secondary	Depth of ANC Nadir in Cycle 1	Depth of ANC nadir was defined as the lowest Median ANC value (*10^9/L) after administration of the study drug (SPI-2012 or pegfilgrastim) on any day in Days 1-3 of Cycle 1.	Cycle 1 (each cycle was 21 days)
Secondary	Depth of ANC Nadir in Cycle 2	Depth of ANC nadir was defined as the lowest Median ANC value (*10^9/L) after administration of the study drug (SPI-2012 or pegfilgrastim) on any day in Days 1-3 of Cycle 2.	Cycle 2 (each cycle was 21 days)
Secondary	Depth of ANC Nadir in Cycle 3	Depth of ANC nadir was defined as the lowest Median ANC value (*10^9/L) after administration of the study drug (SPI-2012 or pegfilgrastim) on any day in Days 1-3 of Cycle 3.	Cycle 3 (each cycle was 21 days)
Secondary	Depth of ANC Nadir in Cycle 4	Depth of ANC nadir was defined as the lowest Median ANC value (*10^9/L) after administration of the study drug (SPI-2012 or pegfilgrastim) on any day in Days 1-3 of Cycle 4.	Cycle 4 (each cycle was 21 days)
Secondary	Time to ANC Nadir in Cycle 1	Time to ANC nadir was defined as the time from chemotherapy administration until the occurrence of the ANC nadir.	Cycle 1 (each cycle was 21 days)
Secondary	Time to ANC Nadir in Cycle 2	Time to ANC nadir was defined as the time from chemotherapy administration until the occurrence of the ANC nadir.	Cycle 2 (each cycle was 21 days)
Secondary	Time to ANC Nadir in Cycle 3	Time to ANC nadir was defined as the time from chemotherapy administration until the occurrence of the ANC nadir.	Cycle 3 (each cycle was 21 days)
Secondary	Time to ANC Nadir in Cycle 4	Time to ANC nadir was defined as the time from chemotherapy administration until the occurrence of the ANC nadir.	Cycle 4 (each cycle was 21 days)
Secondary	Percentage of Participants With Febrile Neutropenia (FN) Across All Cycles From Cycle 1 to Cycle 4	FN was defined as a temperature of more than 38.2 degree Celsius (°C) concurrent with an ANC greater than 0.5×10^9/L..	Cycle 1 to Cycle 4 (each cycle was 21 days)
Secondary	Number of Participants With Worst Grade Adverse Events (AEs), Deaths, Other Serious Adverse Events (SAEs), and Other AEs Leading to Discontinuation From Study Therapy, and Worst Grade Laboratory Abnormalities	An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. An SAE was an AE resulting in any of following outcomes or deemed significant for any other reason: death, initial or prolonged inpatient hospitalization, life-threatening experience (immediate risk of dying), persistent or significant disability or incapacity, congenital anomaly. Participants with SAE other than death were reported.AE and Laboratory Abnormalities ("Hematology and Chemistry") were collected and graded as per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03, where Grade 3 refers to severe or medically significant but not immediately life threatening; hospitalization or prolongation of hospitalization indicated and Grade 4 refers to life-threatening consequences; urgent intervention indicated.	From the first dose up to 30 days post last dose of study drug (up to 4 months)
Secondary	Percentage of Participants With Hospitalization Across All Cycles From Cycle 1 to Cycle 4		All cycles from Cycle 1 to Cycle 4 (each cycle was 21 days)
Secondary	Number of Participants With Positive Antibodies for SPI-2012	Serum samples were to be tested in a screening assay for antibodies binding to SPI-2012 using a validated enzyme-linked immunosorbent assay (ELISA). Any serum samples positive for the antibody were to be tested in a confirmatory competitive inhibition assay using two antigens, SPI-2012 or granulocyte colony-stimulating factor (G-CSF), to confirm the presence of antibodies binding to SPI-2012 and to identify samples that were positive for antibodies binding to G-CSF.	Up to the end of the study (Approximately 3.5 months)
Secondary	Time to Reach Maximum Concentration of SPI-2012 (Tmax)	Blood samples were collected at specific time points to determine the serum concentrations of SPI-2012 and to derive pharmacokinetic (PK) parameters.	Pre-dose and at 1, 3, 6, 8, 10, 24, 48, 72, 144, 192, and 312 hours post-dose in Cycle 1 (each cycle was 21 days)
Secondary	Maximum Concentration of SPI-2012 (Cmax)	Blood samples were collected at specific time points to determine the serum concentrations of SPI-2012 and to derive PK parameters.	Pre-dose and at 1, 3, 6, 8, 10, 24, 48, 72, 144, 192, and 312 hours post-dose in Cycle 1 (each cycle was 21 days)
Secondary	Area Under the Serum Concentration-Time Curve From Time Zero to 312 Hours Post-Dose (AUC0-312)	AUC(0-312) is the area under the serum concentration-time curve from time zero to 312 hour post dose calculated by the linear trapezoidal rule. Blood samples were collected at specific time points to determine the serum concentrations of SPI-2012 and to derive PK parameters.	Pre-dose and at 1, 3, 6, 8, 10, 24, 48, 72, 144, 192, and 312 hours post-dose in Cycle 1 (each cycle was 21 days)
Secondary	Half-life of SPI-2012 (t1/2)	t1/2 data were calculated and reported as harmonic mean and pseudo standard deviation (SD). Blood samples were collected at specific time points to determine the serum concentrations of SPI-2012 and to derive PK parameters.	Pre-dose and at 1, 3, 6, 8, 10, 24, 48, 72, 144, 192, and 312 hours post-dose in Cycle 1 (each cycle was 21 days)