NeutropeniaPhase 2NCT01724866
Phase 2 Study of SPI-2012 or Pegfilgrastim for the Management of Neutropenia in Participants With Breast Cancer
A Phase 2 study testing SPI-2012, Pegfilgrastim and Docetaxel in people with Neutropenia, run by Spectrum Pharmaceuticals, Inc at 27 sites in 6 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neutropenia
- What is being tested?
- SPI-2012, Pegfilgrastim and Docetaxel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 148 participants
- Where
- 27 sitesin 6 countries
- Study dates
- 25 Mar 2013to 12 Aug 2014
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
Trial locations and contacts
27 sites in 6 countries.
27 sites in 6 countries
United States10 sites
New York Oncology Hematology, PC
Albany, New York, 12206
Good Samaritan Hospital, Corvallis
Corvallis, Oregon, 97330
California Cancer Associates for Research and Excellence
Fresno, California, 93720
Arizona Center for Cancer Care
Glendale, Arizona, 85306
Kentucky Cancer Clinic
Hazard, Kentucky, 41701
Beaver Medical Group
Highland, California, 92346
California Cancer Associates for Research and Excellence
Los Angeles, California, 92025
Desert Springs Cancer Care
Scottsdale, Arizona, 85255
North Shore Hematology/Oncology Associates
Setauket, New York, 11733
Innovative Clinical Research Institute
Whittier, California, 90603
Australia5 sites
Royal Hobart
Brisbane, 7000
Frankston Hospital
Frankston, Victoria, 3199
Ashford Cancer Center Research
Kurralta Park, 5037
Breast Cancer Research Center, WA
Perth, 6000
Ballarat Oncology & Haematology
Wendouree, 3355
Hungary5 sites
State Health Center
Budapest, 1062
National Institute of Oncology
Budapest, 1122
Uzsoki Hospital
Budapest, 1146
University Debrecen, Oncology Clinic
Debrecen, 4032
Szabolcs - Szatmár - Bereg megyei Kórházak és Egyetemi Oktatókórház
Nyíregyháza
Poland4 sites
Regionalny Szpital Specjalistyczny
Grudziądz, 86-300
Szpital Uniwersytecki w Krakowie
Krakow, 31-501
Dzienny Oddział Chemioterapii
Racibórz, 47-400
MTZ Clinical Research Sp. z o.o.
Warsaw, 02-106
Georgia2 sites
LTD " Cancer Center of Adjara Autonomic Republic"
Batumi, 6000
Ltd ' Medulla - Chemotherapy and Immunotherapy Clinic
Tbilisi, 0186
About this study
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
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.
Read the detailed 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.
- Conditions
- Neutropenia
- Being tested
- SPI-2012, Pegfilgrastim, Docetaxel, Cyclophosphamide
- Medical subject headings
- Neutropenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SPI-2012Drug
Also called Rolontis®, HM10460A, Eflapegrastim
SPI-2012 SC injection.
PegfilgrastimDrug
Also called Neulasta®
Pegfilgrastim SC injection, per manufacturer's Prescribing Information.
DocetaxelDrug
Also called Taxotere
Docetaxel given based on standard dose for chemotherapy.
CyclophosphamideDrug
Also called Cytoxan
Cyclophosphamide given based on standard dose for chemotherapy.
| Study group | Role | What they receive |
|---|---|---|
| Arm 1: SPI-2012 45 µg/kg and Docetaxel + Cyclophosphamide (TC) | Experimental | Participants received SPI-2012 45 microgram/kilogram (µg/kg), subcutaneously (SC) once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:
Docetaxel 75 milligram/ square metre (mg/m^2) intravenous (IV) infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes. Receives: Drug: SPI-2012; Drug: Docetaxel; Drug: Cyclophosphamide |
| Arm 2: SPI-2012 135 µg/kg and Docetaxel + Cyclophosphamide (TC) | Experimental | Participants received SPI-2012 135 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:
Docetaxel 75 mg/m^2 intravenous (IV) infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes. Receives: Drug: SPI-2012; Drug: Docetaxel; Drug: Cyclophosphamide |
| Arm 3: SPI-2012 270 µg/kg and Docetaxel + Cyclophosphamide (TC) | Experimental | Participants received SPI-2012 270 µg/kg, SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:
Docetaxel 75 mg/m^2 intravenous (IV) infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes. Receives: Drug: SPI-2012; Drug: Docetaxel; Drug: Cyclophosphamide |
| Arm 4: Pegfilgrastim and Docetaxel + Cyclophosphamide (TC) | Experimental | Participants received Pegfilgrastim 6 milligram (mg), SC once per cycle on Day 2 of each cycle up to cycle 4 (each cycle was 21 days), approximately 24 hours after the administration of TC chemotherapy. TC chemotherapy was administered on Day 1 of each cycle as follows:
Docetaxel 75 mg/m^2 intravenous (IV) infusion over 60 minutes and Cyclophosphamide 600 mg/m^2 IV infusion over 30-60 minutes. Receives: Drug: Pegfilgrastim; Drug: Docetaxel; Drug: Cyclophosphamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Cycle 1 (each cycle was 21 days)
Secondary outcomes (27)
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.
Measured: Cycle 2 (each cycle was 21 days)
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.
Measured: Cycle 3 (each cycle was 21 days)
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.
Measured: Cycle 4 (each cycle was 21 days)
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.
Measured: Cycle 1 (each cycle was 21 days)
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.
Measured: Cycle 2 (each cycle was 21 days)
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.
Measured: Cycle 3 (each cycle was 21 days)
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.
Measured: Cycle 4 (each cycle was 21 days)
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.
Measured: Cycle 1 (each cycle was 21 days)
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.
Measured: Cycle 2 (each cycle was 21 days)
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.
Measured: Cycle 3 (each cycle was 21 days)
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.
Measured: Cycle 4 (each cycle was 21 days)
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.
Measured: Cycle 1 (each cycle was 21 days)
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.
Measured: Cycle 2 (each cycle was 21 days)
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.
Measured: Cycle 3 (each cycle was 21 days)
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.
Measured: Cycle 4 (each cycle was 21 days)
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.
Measured: Cycle 1 (each cycle was 21 days)
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.
Measured: Cycle 2 (each cycle was 21 days)
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.
Measured: Cycle 3 (each cycle was 21 days)
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.
Measured: Cycle 4 (each cycle was 21 days)
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..
Measured: Cycle 1 to Cycle 4 (each cycle was 21 days)
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.
Measured: From the first dose up to 30 days post last dose of study drug (up to 4 months)
Percentage of Participants With Hospitalization Across All Cycles From Cycle 1 to Cycle 4
Measured: All cycles from Cycle 1 to Cycle 4 (each cycle was 21 days)
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.
Measured: Up to the end of the study (Approximately 3.5 months)
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Nov 2012 (estimated)
- Study start25 Mar 2013
- Primary completion12 Aug 2014
- Study completion12 Aug 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for NeutropeniaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 148 participants (actual)
Sponsor and investigators
- Lead sponsor
- Spectrum Pharmaceuticals, Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01724866
- Sponsor's protocol ID
- SPI-GCF-12-201
- Other IDs
- 2013-003094-10
- Status last verified
- Mar 2022
- First submitted
- 24 Oct 2012
- Last updated
- 15 Apr 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Vacirca JL, Chan A, Mezei K, Adoo CS, Papai Z, McGregor K, Okera M, Horvath Z, Landherr L, Hanslik J, Hager SJ, Ibrahim EN, Rostom M, Bhat G, Choi MR, Reddy G, Tedesco KL, Agajanian R, Lang I, Schwartzberg LS. An open-label, dose-ranging study of Rolontis, a novel long-acting myeloid growth factor, in breast cancer. Cancer Med. 2018 May;7(5):1660-1669. doi: 10.1002/cam4.1388. Epub 2018 Mar 23.
PubMed 29573207