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

Browse trials for

• Neutropenia 396

Study arms

• Experimental
  Arm 1: SPI-2012 45 µg/kg and Docetaxel + Cyclophosphamide (TC)

  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.

  Drug: SPI-2012 · Drug: Docetaxel · Drug: Cyclophosphamide

• Experimental
  Arm 2: SPI-2012 135 µg/kg and Docetaxel + Cyclophosphamide (TC)

  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.

  Drug: SPI-2012 · Drug: Docetaxel · Drug: Cyclophosphamide

• Experimental
  Arm 3: SPI-2012 270 µg/kg and Docetaxel + Cyclophosphamide (TC)

  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.

  Drug: SPI-2012 · Drug: Docetaxel · Drug: Cyclophosphamide

• Experimental
  Arm 4: Pegfilgrastim and Docetaxel + Cyclophosphamide (TC)

  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.

  Drug: Pegfilgrastim · Drug: Docetaxel · Drug: Cyclophosphamide

Interventions

• DrugSPI-2012

  SPI-2012 SC injection.

  Also known as: Rolontis®, HM10460A, Eflapegrastim

• DrugPegfilgrastim

  Pegfilgrastim SC injection, per manufacturer's Prescribing Information.

  Also known as: Neulasta®

• DrugDocetaxel

  Docetaxel given based on standard dose for chemotherapy.

  Also known as: Taxotere

• DrugCyclophosphamide

  Cyclophosphamide given based on standard dose for chemotherapy.

  Also known as: Cytoxan

Primary outcomes

1. 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.

   Time frame: Cycle 1 (each cycle was 21 days)

Secondary outcomes

1. 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.

   Time frame: Cycle 2 (each cycle was 21 days)

2. 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.

   Time frame: Cycle 3 (each cycle was 21 days)

3. 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.

   Time frame: Cycle 4 (each cycle was 21 days)

4. 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.

   Time frame: Cycle 1 (each cycle was 21 days)

5. 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.

   Time frame: Cycle 2 (each cycle was 21 days)

6. 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.

   Time frame: Cycle 3 (each cycle was 21 days)

7. 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.

   Time frame: Cycle 4 (each cycle was 21 days)

8. 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.

   Time frame: Cycle 1 (each cycle was 21 days)

9. 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.

   Time frame: Cycle 2 (each cycle was 21 days)

10. 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.

    Time frame: Cycle 3 (each cycle was 21 days)

11. 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.

    Time frame: Cycle 4 (each cycle was 21 days)

12. 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.

    Time frame: Cycle 1 (each cycle was 21 days)

13. 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.

    Time frame: Cycle 2 (each cycle was 21 days)

14. 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.

    Time frame: Cycle 3 (each cycle was 21 days)

15. 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.

    Time frame: Cycle 4 (each cycle was 21 days)

16. 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.

    Time frame: Cycle 1 (each cycle was 21 days)

17. 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.

    Time frame: Cycle 2 (each cycle was 21 days)

18. 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.

    Time frame: Cycle 3 (each cycle was 21 days)

19. 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.

    Time frame: Cycle 4 (each cycle was 21 days)

20. 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..

    Time frame: Cycle 1 to Cycle 4 (each cycle was 21 days)

21. 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.

    Time frame: From the first dose up to 30 days post last dose of study drug (up to 4 months)

22. Percentage of Participants With Hospitalization Across All Cycles From Cycle 1 to Cycle 4

    Time frame: All cycles from Cycle 1 to Cycle 4 (each cycle was 21 days)

23. 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.

    Time frame: Up to the end of the study (Approximately 3.5 months)

24. 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.

    Time frame: 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)

25. 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.

    Time frame: 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)

26. 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.

    Time frame: 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)

27. 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.

    Time frame: 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)

Baseline characteristics

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 ↗

Individual participant data

Plan to share: No