The primary purpose of this study is to compare the percentage of patients with Duration of Severe Neutropenia (DSN) =0 in patients treated with: Docetaxel, doxorubicin, and cyclophosphamide (TAC) + pegfilgrastim versus Docetaxel, doxorubicin, and cyclophosphamide (TAC) + combination plinabulin/pegfilgrastim Severe neutropenia is an absolute neutrophil count (ANC) \<0.5 × 10\^9/L. Docetaxel, doxorubicin, and cyclophosphamide (TAC) will be used as the chemotherapy in this study.
This is a multi-center randomized study, double-blind phase 3 trial. Approximately 222 patients are planned to be enrolled in Phase 3. Docetaxel, doxorubicin, and cyclophosphamide (TAC) will be used as the chemotherapy in this study. These agents are among the most active and commonly used chemotherapeutic agents employed for treating patients with breast carcinoma. In particular, TAC chemotherapy has been used for the adjuvant treatment of HER2 negative early breast cancer patients with node positive disease as well as for node negative breast cancer patients who have a high risk of recurrence. Plinabulin is a novel small molecule that is being developed for the mitigation of chemotherapy-induced neutropenia. Administered by IV infusion on the same day of (approximately 1 hour after) chemotherapy (TAC), plinabulin will be given in a single dose per cycle. Plinabulin is being studied to see if it is a convenient alternative to G-CSF, pegfilgrastim, for the prevention of chemotherapy-induced neutropenia. In this trial, treatment will be double blinded, approximately 222 patients with breast cancer are expected to be enrolled. Patients are randomly assigned to one of the treatment arms, with 111 patients enrolled in each arm, with the arm designation and planned intervention as follows: Arm 1: TAC + pegfilgrastim (6.0 mg) + placebo matching plinabulin. Arm 2: TAC + pegfilgrastim (6.0 mg) + plinabulin (40 mg). Cycles 1 to 4 will consist of TAC (or TC for Cycles 2 to 4) administered IV on Day 1 every 21 days. Patients will receive a single dose of plinabulin or placebo IV over 30 minutes (±5 minutes) in a double blinded manner, 30 minutes after the end of the TAC (or TC for Cycles 2 to 4) infusion. On Day 2 of each cycle (≥24 hours after completing chemotherapy), all patients will receive a single dose of pegfilgrastim (6.0 mg). The long-term safety follow-up through patients contacts by phone calls, letters or electronic means; or medical records reviews will be conducted to all subjects approximately every 6 months up to 5 years to monitor long term safety of plinabulin.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
SUPPORTIVE_CARE
Masking
TRIPLE
Enrollment
221
PEGFILGRASTIM is a long-acting granulocyte colony-stimulating factor that stimulates the growth of neutrophils, to reduce the incidence of fever and infection in patients with certain types of cancer who are receiving chemotherapy that affects the bone marrow.
Plinabulin (BPI-2358) is a synthetic, low molecular weight, new chemical entity that belongs to the diketopiperazine class of compounds. Plinabulin is intended for intravenous (IV) infusion and is diluted in D5W and administered for 30 minutes (± 5 minutes).
Placebo 250 ml D5W to match the administration of plinabulin diluted in 250 ml D5W
No. 1 Banshandong Road
Hangzhou, Gongshu District, China
Percentage of patients with Duration of Severe Neutropenia (DSN) =0
DSN is defined as Days of Grade 4 Neutropenia (ANC less than 0.5 X 109/L)
Time frame: Duration of Grade 4 neutropenia assessed during the first cycle (21 days)
Mean DSN assessment
DSN is defined as Days of Grade 4 Neutropenia (ANC less than 0.5 X 109/L)
Time frame: From day 1 to day 8 in first cycle (21 days)
Mean ANC nadir
record and evaluate the lowest ANC value
Time frame: Duration of first cycle (21 days)
Percentage of Patients without grade 3 and grade 4 neutropenia
ANC less than 1 x 109/L and above 0.5x 109/L is defined as grade 3 neutropenia. ANC less than 0.5 X 109/L is defined as grade 4 neutropenia.
Time frame: Duration of first cycle (21 days)
Mean DSN assessment within 15 days
To evaluate the effect of Plinabulin related to DSN within 15 days
Time frame: From day 1 to day 15 in the first cycle (21 days)
Average change in bone pain
Record the bone pain score from the numerical rating scale (NRS)
Time frame: From -1 day over the observational period
Rate of composite risks
Composite risks includes infection, FN, hospitalization, significant disability, life threatening and death
Time frame: Duration of all 4 cycle (21 days)
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Docetaxel is a type of chemotherapy medicine called an taxane. Doxorubicin is a type of chemotherapy medicine called an anthracycline. Cyclophosphamide is a type of chemotherapy medicine called an alkylating agent.
Cancer Center of Guangzhou Medical University
Guangzhou, Guangdong, China
Cancer Center of Guangzhou Medical University Breast Oncology
Guangzhou, Guangzhou, China
Harbin Medical University Cancer Hospital
Harbin, Harbin, China
Fourth Hospital of Hebei Medical University Breast cancer department
Shijiazhuang, Hebei, China
China-Japan Union Hospital of Jilin University Tumor department of Hematology
Changchun, Jilin, China
Liaoning Cancer Hospital & Institute
Shenyang, Shenyang, China
Dnipropetrovsk City Multifunctional Hospital #4 Oncology Department
Dnipro, Ukraine
Prykarpatskiy Regional Oncological Center
Ivano-Frankivsk, Ukraine
Regional Clinical Oncology Center
Kharkiv, Ukraine
...and 10 more locations
Percentage of patients with relative dose intensity < 85%
Assess the percentage of patients with RDI \< 85%
Time frame: Duration of all 4 cycle (21 days)