Clinical trial NCT01724866: Phase 2 Study of SPI-2012 or Pegfilgrastim for the Management of Neutropenia in Participants With Breast Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Neutropenia
Lead sponsor: Spectrum Pharmaceuticals, Inc
Sponsor class: INDUSTRY
First posted: 2012-11-12
Enrollment: 148
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Duration of Severe Neutropenia (DSN) in Cycle 1
timeFrame: Cycle 1 (each cycle was 21 days)
Secondary outcomes:
measure: Duration of DSN in Cycle 2
timeFrame: Cycle 2 (each cycle was 21 days)
measure: Duration of DSN in Cycle 3
timeFrame: Cycle 3 (each cycle was 21 days)
measure: Duration of DSN in Cycle 4
timeFrame: Cycle 4 (each cycle was 21 days)
measure: Time to ANC Recovery in Cycle 1
timeFrame: Cycle 1 (each cycle was 21 days)
measure: Time to ANC Recovery in Cycle 2
timeFrame: Cycle 2 (each cycle was 21 days)
measure: Time to ANC Recovery in Cycle 3
timeFrame: Cycle 3 (each cycle was 21 days)
measure: Time to ANC Recovery in Cycle 4
timeFrame: Cycle 4 (each cycle was 21 days)
measure: Absolute Neutrophil Count (ANC) Nadir Overtime in Cycle 1
timeFrame: Cycle 1 (each cycle was 21 days)
measure: Absolute ANC Nadir Overtime in Cycle 2
timeFrame: Cycle 2 (each cycle was 21 days)
measure: Absolute ANC Nadir Overtime in Cycle 3
timeFrame: Cycle 3 (each cycle was 21 days)
measure: Absolute ANC Nadir Overtime in Cycle 4
timeFrame: Cycle 4 (each cycle was 21 days)
measure: Depth of ANC Nadir in Cycle 1
timeFrame: Cycle 1 (each cycle was 21 days)
measure: Depth of ANC Nadir in Cycle 2
timeFrame: Cycle 2 (each cycle was 21 days)
measure: Depth of ANC Nadir in Cycle 3
timeFrame: Cycle 3 (each cycle was 21 days)
measure: Depth of ANC Nadir in Cycle 4
timeFrame: Cycle 4 (each cycle was 21 days)
measure: Time to ANC Nadir in Cycle 1
timeFrame: Cycle 1 (each cycle was 21 days)
measure: Time to ANC Nadir in Cycle 2
timeFrame: Cycle 2 (each cycle was 21 days)
measure: Time to ANC Nadir in Cycle 3
timeFrame: Cycle 3 (each cycle was 21 days)
measure: Time to ANC Nadir in Cycle 4
timeFrame: Cycle 4 (each cycle was 21 days)
measure: Percentage of Participants With Febrile Neutropenia (FN) Across All Cycles From Cycle 1 to Cycle 4
timeFrame: Cycle 1 to Cycle 4 (each cycle was 21 days)
measure: 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
timeFrame: From the first dose up to 30 days post last dose of study drug (up to 4 months)
measure: Percentage of Participants With Hospitalization Across All Cycles From Cycle 1 to Cycle 4
timeFrame: All cycles from Cycle 1 to Cycle 4 (each cycle was 21 days)
measure: Number of Participants With Positive Antibodies for SPI-2012
timeFrame: Up to the end of the study (Approximately 3.5 months)
measure: Time to Reach Maximum Concentration of SPI-2012 (Tmax)
timeFrame: 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)
measure: Maximum Concentration of SPI-2012 (Cmax)
timeFrame: 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)
measure: Area Under the Serum Concentration-Time Curve From Time Zero to 312 Hours Post-Dose (AUC0-312)
timeFrame: 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)
measure: Half-life of SPI-2012 (t1/2)
timeFrame: 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)
Other outcomes:
Locations:
city: Glendale
country: United States
facility: Arizona Center for Cancer Care
state: Arizona
city: Scottsdale
country: United States
facility: Desert Springs Cancer Care
state: Arizona
city: Fresno
country: United States
facility: California Cancer Associates for Research and Excellence
state: California
city: Highland
country: United States
facility: Beaver Medical Group
state: California
city: Los Angeles
country: United States
facility: California Cancer Associates for Research and Excellence
state: California
city: Whittier
country: United States
facility: Innovative Clinical Research Institute
state: California
city: Hazard
country: United States
facility: Kentucky Cancer Clinic
state: Kentucky
city: Albany
country: United States
facility: New York Oncology Hematology, PC
state: New York
city: Setauket
country: United States
facility: North Shore Hematology/Oncology Associates
state: New York
city: Corvallis
country: United States
facility: Good Samaritan Hospital, Corvallis
state: Oregon
city: Frankston
country: Australia
facility: Frankston Hospital
state: Victoria
city: Brisbane
country: Australia
facility: Royal Hobart
city: Kurralta Park
country: Australia
facility: Ashford Cancer Center Research
city: Perth
country: Australia
facility: Breast Cancer Research Center, WA
city: Wendouree
country: Australia
facility: Ballarat Oncology & Haematology
city: Batumi
country: Georgia
facility: LTD " Cancer Center of Adjara Autonomic Republic"
city: Tbilisi
country: Georgia
facility: Ltd ' Medulla - Chemotherapy and Immunotherapy Clinic
city: Budapest
country: Hungary
facility: State Health Center
city: Budapest
country: Hungary
facility: National Institute of Oncology
city: Budapest
country: Hungary
facility: Uzsoki Hospital
city: Debrecen
country: Hungary
facility: University Debrecen, Oncology Clinic
city: Nyíregyháza
country: Hungary
facility: Szabolcs - Szatmár - Bereg megyei Kórházak és Egyetemi Oktatókórház
city: Zefat
country: Israel
facility: Ziv Medical Center
city: Grudziądz
country: Poland
facility: Regionalny Szpital Specjalistyczny
city: Kraków
country: Poland
facility: Szpital Uniwersytecki w Krakowie
city: Racibórz
country: Poland
facility: Dzienny Oddział Chemioterapii
city: Warszawa
country: Poland
facility: MTZ Clinical Research Sp. z o.o.
Study officials:
References:
citation: 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.