TriangleNCT02643420 · CITED IN SOURCE DOCUMENTS
SPI-2012 vs Pegfilgrastim in the Management of Neutropenia in Participants With Breast Cancer With Docetaxel and Cyclophosphamide (ADVANCE)
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE3
- Status at capture
- COMPLETED
- Registry last update
- 2022-03-02
The purpose of this study was to compare the efficacy of a single dose 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) in Cycle 1.
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
Duration of Severe Neutropenia (DSN) in Cycle 1
Time to Absolute Neutrophil Count (ANC) Recovery in Cycle 1
Depth of Absolute Neutrophil Count (ANC) Nadir in Cycle 1
Number of Participants With Febrile Neutropenia (FN) in Cycle 1
Duration of Severe Neutropenia in Cycle 2, 3 and 4
Number of Participants With Neutropenic Complications in Cycle 1
Number of Participants With Febrile Neutropenia in Cycles 2, 3, and 4
Relative Dose Intensity (RDI) of TC (Docetaxel + Cyclophosphamide) in Cycles 1 to 4
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Adverse events
Limitations, agreements, and source contact
Who could take part
- eligibility Criteria
- 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 neoadjuvant TC chemotherapy * Eastern Cooperative Oncology Group (ECOG) performance score ≤ 2 * Absolute neutrophil count (ANC) ≥ 1.5×10\^9/L * Platelet count ≥ 100×10\^9/L * Hemoglobin \> 9 g/dL * Creatinine clearance \> 50 mL/min * Total bilirubin ≤ 1.5 mg/dL * Aspartate Aminotransferase per Serum Glutamic-Oxaloacetic Transaminase (AST/SGOT) and Alanine Aminotransferase per Serum Glutamic-Pyruvic Transaminase (ALT/SGPT) ≤ 2.5× Upper Limit of Normal (ULN). * 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 or metastatic breast cancer * Known sensitivity to E. coli -derived products or to any products to be administered during dosing * 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 serious underlying medical condition that would impair ability to receive protocol treatment * Prior bone marrow or stem cell transplant * Use of 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
- healthy Volunteers
- false
- minimum Age
- 18 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- Participants received SPI-2012 13.2 milligram (mg)/0.6 milliliter (mL) (3.6 mg Granulocyte Colony-Stimulating Factor \[G-CSF\]) fixed-dose subcutaneous (SC) injection once per cycle on Day 2 of each cycle up to Cycle 4 (each cycle was 21 days), approximately 24-26 hours after TC chemotherapy administration. TC chemotherapy was administered on Day 1 of each cycle and included Docetaxel 75 mg/m\^2 intravenous (IV) infusion and Cyclophosphamide 600 mg/m\^2 IV infusion per institute's standard of care.
- intervention Names
- Drug: SPI-2012
- Drug: Docetaxel
- Drug: Cyclophosphamide
- label
- Arm 1: SPI-2012 and Docetaxel + Cyclophosphamide (TC)
- type
- EXPERIMENTAL
- description
- Participants received pegfilgrastim 6 mg SC injection once per cycle on Day 2 of each cycle up to Cycle 4 (each cycle was 21 days), approximately 24-26 hours after TC chemotherapy administration. TC chemotherapy on Day 1 of each cycle included Docetaxel 75 mg/m\^2 IV infusion and Cyclophosphamide 600 mg/m\^2 IV infusion per institute's standard of care.
- intervention Names
- Drug: Pegfilgrastim
- Drug: Docetaxel
- Drug: Cyclophosphamide
- label
- Arm 2: Pegfilgrastim and Docetaxel + Cyclophosphamide (TC)
- type
- EXPERIMENTAL
- interventions
- arm Group Labels
- Arm 1: SPI-2012 and Docetaxel + Cyclophosphamide (TC)
- description
- Single-use syringes for subcutaneous injection, administered on Day 2 of each cycle
- name
- SPI-2012
- other Names
- Rolontis®
- Eflapegrastim
- (HM10460A)
- type
- DRUG
- arm Group Labels
- Arm 2: Pegfilgrastim and Docetaxel + Cyclophosphamide (TC)
- description
- Single-dose subcutaneous injection administered on Day 2 of each cycle
- name
- Pegfilgrastim
- other Names
- Neulasta®
- type
- DRUG
- arm Group Labels
- Arm 1: SPI-2012 and Docetaxel + Cyclophosphamide (TC)
- Arm 2: Pegfilgrastim and Docetaxel + Cyclophosphamide (TC)
- description
- Standard therapy
- name
- Docetaxel
- other Names
- Taxotere
- type
- DRUG
- arm Group Labels
- Arm 1: SPI-2012 and Docetaxel + Cyclophosphamide (TC)
- Arm 2: Pegfilgrastim and Docetaxel + Cyclophosphamide (TC)
- description
- Standard therapy
- name
- Cyclophosphamide
- other Names
- Cytoxan
- type
- DRUG
Study design
- allocation
- RANDOMIZED
- intervention Model
- PARALLEL
- masking Info
- masking
- NONE
- primary Purpose
- TREATMENT
Enrollment
- count
- 406
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- DSN was defined as the number of days of severe neutropenia (absolute neutrophil count \[ANC\] \<0.5×10\^9/L), after the administration of study drug in Cycle 1.
- measure
- Duration of Severe Neutropenia (DSN) in Cycle 1
- time Frame
- Day 1 and Days 4-15 in Cycle 1 (each cycle was 21 days)
- secondary Outcomes
- description
- Time to ANC Recovery was defined as the time from chemotherapy administration until ANC increased to ≥1.5×10\^9/L after the expected nadir within Cycle 1. Time to ANC recovery was assigned as 0 for participants whose ANC value never dropped below 1.5 x10\^9/L.
- measure
- Time to Absolute Neutrophil Count (ANC) Recovery in Cycle 1
- time Frame
- Day 1 and Days 4, 15 in Cycle 1 (each cycle was 21 days)
- description
- Depth of ANC Nadir was defined as the lowest ANC value after administration of study drug (SPI-2012 or Pegfilgrastim) in Cycle 1.
- measure
- Depth of Absolute Neutrophil Count (ANC) Nadir in Cycle 1
- time Frame
- Day 1 and Days 4, 15 in Cycle 1 (each cycle was 21 days)
- description
- FN was defined as an oral temperature \> 38.3 degrees Celsius (C) (101.0 degrees Fahrenheit \[F\]) or two consecutive readings of \>=38.0 degrees C (100.4 degrees F) for 2 hours and ANC \<1.0×10\^9/L.
- measure
- Number of Participants With Febrile Neutropenia (FN) in Cycle 1
- time Frame
- Day 1 and Days 4, 15 in Cycle 1 (each cycle was 21 days)
- description
- DSN was defined as the number of days of severe neutropenia (ANC \<0.5×10\^9 /L) from the first occurrence of an ANC below the threshold in Cycles 2, 3, and 4.
- measure
- Duration of Severe Neutropenia in Cycle 2, 3 and 4
- time Frame
- Days 1, 4, 7, 10, and 15 in cycles 2, 3, and 4 (each cycle was 21 days)
- description
- Neutropenic complications refer to hospitalizations due to neutropenic events and/or the use of anti-infectives due to neutropenia.
- measure
- Number of Participants With Neutropenic Complications in Cycle 1
- time Frame
- Day 1 and Days 4, 15 in Cycle 1 (each cycle was 21 days)
- description
- FN was defined as an oral temperature \> 38.3 degrees C (101.0 degrees Fahrenheit \[F\]) or two consecutive readings of \>=38.0 degrees C (100.4 degrees F) for 2 hours and ANC \<1.0×10\^9/L.
- measure
- Number of Participants With Febrile Neutropenia in Cycles 2, 3, and 4
- time Frame
- Days 1, 4, 7, 10, and 15 of Cycles 2, 3, and 4 (each cycle was 21 days)
- description
- RDI was defined as the percentage of the planned dose that each participant actually received during the study, expressed as the total dose received, divided by the total dose planned and 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.
- measure
- Relative Dose Intensity (RDI) of TC (Docetaxel + Cyclophosphamide) in Cycles 1 to 4
- time Frame
- Cycles 1 to 4 (each cycle was 21 days)
- description
- 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 for Treatment Period is defined as adverse event with an onset date on or after the date of study drug administration through the end of treatment. TEAE for follow up is defined as any new onset or ongoing AE at the end of Treatment. 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.
- measure
- Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
- time Frame
- From the first dose of TC (Docetaxel + Cyclophosphamide) until 12 months after the last dose of study treatment (up to approximately 34 months)
Full study description
- brief Summary
- The purpose of this study was to compare the efficacy of a single dose 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) in Cycle 1.
- detailed Description
- This was a Phase 3, randomized, open-label, active-controlled, multicenter study to compare the efficacy and safety of SPI-2012 vs pegfilgrastim in participants with breast cancer treated with TC chemotherapy. Each cycle was 21 days. Four cycles were evaluated in 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).
Source references
Source notices and limitations
Discovery and provenance
- release id
- ctgov-registry-7ad944f6deaf1f5cd6122126
- edge id
- nct-edge-4b5eb9b4d8da9334770e
- requested nct id
- NCT02643420
- primary nct id
- NCT02643420
- source kind
- fda_spl_label
- source record id
- ef8eef01-b278-484e-b4d4-85905e756674
- source file sha256
- 24c521d95bd19e54a354ae592997052a3a1b19254da1496b3a98a5e9bac4ed08
- payload sha256
- 4c59da1f833db2cb104990675499161f498cff433fd6702027ae136af8eff50e
- payload
- application numbers
- BLA761148
- clinical indication matching status
- not_inferred
- end exclusive
- true
- id
- nct-edge-4b5eb9b4d8da9334770e
- link basis
- explicit_NCT_identifier_in_acquired_source
- nct id
- NCT02643420
- occurrences
- context exact
- ving myelosuppressive anti-cancer drugs was evaluated in two 1:1 randomized, open-label, active-controlled non-inferiority studies of similar design (Study 1 [ NCT02643420 ] and Study 2 [ NCT02953340 ]) that enrolled a total of 643 patients with early-stage breast cancer. Docetaxel 75 mg/m] and Study 2 [NCT02953340]) that enrolle
- end
- 401
- exact text
- NCT02643420
- start
- 390
- offset unit
- unicode_code_points
- source file
- /tmp/cancer-full-research/indications/raw/labels-00700.json
- source file sha256
- 24c521d95bd19e54a354ae592997052a3a1b19254da1496b3a98a5e9bac4ed08
- source json pointer
- /results/97/clinical_studies/0
- source kind
- fda_spl_label
- source record id
- ef8eef01-b278-484e-b4d4-85905e756674
- source string basis
- parsed_JSON_string_unmodified
- source string sha256
- 4c5cb7999e2c0a60446a51fdda665cf2d6ace452b116e3f17dc81f573735a780
- spl effective time
- 20260211
- spl set id
- 2dc62c46-bb10-4a62-a459-d3eeeb6dd82f
- release id
- ctgov-registry-7ad944f6deaf1f5cd6122126
- edge id
- nct-edge-e912dd80b393d24dfd50
- requested nct id
- NCT02643420
- primary nct id
- NCT02643420
- source kind
- fda_spl_label
- source record id
- 9209fc63-aee3-43dc-9bc6-16c5ed73d858
- source file sha256
- 424ccf5bc67db0a96ee2c35ed913dd5894642716182773d81ca19cdfb9ba32f3
- payload sha256
- 23d8cc67d883b732b5bf1883ddc1153c5d3c784091d6905b916211bc23293d00
- payload
- application numbers
- BLA761148
- clinical indication matching status
- not_inferred
- end exclusive
- true
- id
- nct-edge-e912dd80b393d24dfd50
- link basis
- explicit_NCT_identifier_in_acquired_source
- nct id
- NCT02643420
- occurrences
- context exact
- iving myelosuppressive anti-cancer drugs was evaluated in two 1:1 randomized, open-label, active-controlled non-inferiority studies of similar design (Study 1 [NCT02643420] and Study 2 [NCT02953340]) that enrolled a total of 643 patients with early-stage breast cancer. Docetaxel 75 mg/m 2 and cyclophosphamide 600 mg/m 2 (TC) were
- end
- 400
- exact text
- NCT02643420
- start
- 389
- offset unit
- unicode_code_points
- source file
- /tmp/cancer-full-research/indications/raw/labels-00500.json
- source file sha256
- 424ccf5bc67db0a96ee2c35ed913dd5894642716182773d81ca19cdfb9ba32f3
- source json pointer
- /results/36/clinical_studies/0
- source kind
- fda_spl_label
- source record id
- 9209fc63-aee3-43dc-9bc6-16c5ed73d858
- source string basis
- parsed_JSON_string_unmodified
- source string sha256
- 10554ddf8745b2faf1a5f4cd755523d014381db9e5a8795e263dae26601ffaad
- spl effective time
- 20260218
- spl set id
- 6e436115-62e7-4729-aeb0-ff78ea685206
Preserved source evidence · Not medical advice