SPI-2012 vs Pegfilgrastim in the Management of Neutropenia in Participants With Breast Cancer With Docetaxel and Cyclophosphamide (ADVANCE)

Study Overview
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Brief Summary
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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
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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).

Official Title
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RAnDomized Trial of SPI-2012 Versus Pegfilgrastim in the Management of Chemotherapy Induced Neutropenia in Breast CANCEr Patients Receiving Docetaxel and Cyclophosphamide (TC) (ADVANCE)

Conditions
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Neutropenia, Breast Cancer

Intervention / Treatment
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* Drug: SPI-2012
* Drug: Pegfilgrastim
* Drug: Docetaxel
* Drug: Cyclophosphamide


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1: SPI-2012 and Docetaxel + Cyclophosphamide (TC)<br>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. | Drug: SPI-2012<br>* Single-use syringes for subcutaneous injection, administered on Day 2 of each cycle<br>* Other names: (HM10460A);Drug: Docetaxel<br>* Standard therapy<br>* Other names: Taxotere;Drug: Cyclophosphamide<br>* Standard therapy<br>* Other names: Cytoxan;|
| Experimental: Arm 2: Pegfilgrastim and Docetaxel + Cyclophosphamide (TC)<br>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. | Drug: Pegfilgrastim<br>* Single-dose subcutaneous injection administered on Day 2 of each cycle<br>* Other names: Neulasta®;Drug: Docetaxel<br>* Standard therapy<br>* Other names: Taxotere;Drug: Cyclophosphamide<br>* Standard therapy<br>* Other names: Cytoxan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Severe Neutropenia (DSN) in Cycle 1 | 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. | Day 1 and Days 4-15 in Cycle 1 (each cycle was 21 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Absolute Neutrophil Count (ANC) Recovery in Cycle 1 | 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. | Day 1 and Days 4, 15 in Cycle 1 (each cycle was 21 days) | 
| Depth of Absolute Neutrophil Count (ANC) Nadir in Cycle 1 | Depth of ANC Nadir was defined as the lowest ANC value after administration of study drug (SPI-2012 or Pegfilgrastim) in Cycle 1. | Day 1 and Days 4, 15 in Cycle 1 (each cycle was 21 days) | 
| Number of Participants With Febrile Neutropenia (FN) in Cycle 1 | 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. | Day 1 and Days 4, 15 in Cycle 1 (each cycle was 21 days) | 
| Duration of Severe Neutropenia in Cycle 2, 3 and 4 | 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. | Days 1, 4, 7, 10, and 15 in cycles 2, 3, and 4 (each cycle was 21 days) | 
| Number of Participants With Neutropenic Complications in Cycle 1 | Neutropenic complications refer to hospitalizations due to neutropenic events and/or the use of anti-infectives due to neutropenia. | Day 1 and Days 4, 15 in Cycle 1 (each cycle was 21 days) | 
| Number of Participants With Febrile Neutropenia in Cycles 2, 3, and 4 | 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. | Days 1, 4, 7, 10, and 15 of Cycles 2, 3, and 4 (each cycle was 21 days) | 
| Relative Dose Intensity (RDI) of TC (Docetaxel + Cyclophosphamide) in Cycles 1 to 4 | 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. | Cycles 1 to 4 (each cycle was 21 days) | 
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | 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. | From the first dose of TC (Docetaxel + Cyclophosphamide) until 12 months after the last dose of study treatment (up to approximately 34 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neutropenia, Breast Cancer, Long-acting Myeloid Growth Factor, Early Stage Breast Cancer, Docetaxel + Cyclophosphamide (TC) chemotherapy