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

Spectrum Pharmaceuticals

Status and phase: Completed; Phase 3

Conditions: Breast Cancer; Neutropenia

Treatments: Drug: Cyclophosphamide; Drug: Pegfilgrastim; Drug: Docetaxel; Drug: SPI-2012

Study type: Interventional

Funder types: Industry

Identifiers

NCT02643420

SPI-GCF-301

Details and patient eligibility

About

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.

Full 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).

Enrollment: 406 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

406 participants in 2 patient groups

Arm 1: SPI-2012 and Docetaxel + Cyclophosphamide (TC)

Experimental group

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.

Treatment:

Drug: SPI-2012

Drug: Docetaxel

Drug: Cyclophosphamide

Arm 2: Pegfilgrastim and Docetaxel + Cyclophosphamide (TC)

Experimental group

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.

Treatment:

Drug: Docetaxel

Drug: Cyclophosphamide

Drug: Pegfilgrastim