NCT04227990

Plinabulin iv Solution in Prevention of TAC Induced Neutropenia

Plinabulin vs. Pegfilgrastim in Reducing the Duration of Severe Neutropenia in Breast Cancer Patients Receiving Myelosuppressive Chemotherapy With Docetaxel, Doxorubicin, and Cyclophosphamide (TAC)

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 115 (actual)
• Sponsor: BeyondSpring Pharmaceuticals Inc. · Industry
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The primary purpose of this study is to compare the duration of severe neutropenia (DSN) in patients treated with: Docetaxel, doxorubicin, and cyclophosphamide (TAC) + pegfilgrastim versus Docetaxel, doxorubicin, and cyclophosphamide (TAC) + monotheray plinabulin or 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.

Detailed description

This is a multi-center randomized study, Phase 2 study. 115 patients were enrolled in Phase 2. Two regimens were evaluated in Phase 2: a plinabulin monotherapy regimen and a combination therapy regimen of plinabulin + pegfilgrastim. The monotherapy regimen includes 4 arms: pegfilgrastim 6.0 mg alone; and 10, 20, or 30 mg/m2 plinabulin. The combination regimen includes 4 arms: pegfilgrastim 6.0 mg alone; and 20 mg/m2 plinabulin + pegfilgrastim 1.5, 3, or 6.0 mg. The pegfilgrastim 6.0 mg alone arm is the control arm for comparison with the monotherapy and combination therapy arms for the interim evaluation. The purpose of this study is to compare the duration of severe neutropenia (DSN) in patients with early stage (Stage I and II) and Stage III breast cancer (node positive or node negative with high risk of recurrence) receiving docetaxel, doxorubicin, and cyclophosphamide (TAC) and monotherapy plinabulin or combination therapy plinabulin/pegfilgrastim. Severe neutropenia is an absolute neutrophil count (ANC) \<0.5 × 10\^9/L. Docetaxel, doxorubicin, and cyclophosphamide (TAC) were 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 was 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. 64 patients were enrolled for monotherapy evaluation and 51 patients were enrolled for the combination therapy Arm 5, 6 and 7 for efficacy and safety evaluation. The arm designation and planned intervention is as follows: For monotherapy: Arm 1: TAC + pegfilgrastim (6.0 mg) Arm 2: TAC + plinabulin (10 mg/m2). Arm 3: TAC + plinabulin (20 mg/m2). Arm 4: TAC + plinabulin (30 mg/m2). For combination therapy: Arm 1: TAC + pegfilgrastim (6.0 mg) Arm 5: TAC + plinabulin (20 mg/m2) + pegfilgrastim (1.5 mg) Arm 6: TAC + plinabulin (20 mg/m2) + pegfilgrastim (3.0 mg) Arm 7: TAC + plinabulin (20 mg/m2) + pegfilgrastim (6.0 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 in Arms 2, 3 and 4 will receive a single dose of plinabulin, 30 minutes after the end of the TAC (or TC for Cycles 2 to 4) infusion on Day 1. The plinabulin dose will be infused over 30 minutes (±5 minutes) in Arms 2 and 3 and over 60 minutes (±5 minutes) in Arm 4 (in order to improve tolerability at the higher 30 mg/m2 dose level). On Day 2 of each cycle (≥24 hours after completing chemotherapy) patients in Arm 1 and in combination therapy will receive a single dose of pegfilgrastim (1.5, 3.0, or 6.0 mg) (subcutaneous injection).

Conditions

• Chemotherapy-induced Neutropenia

Interventions

Type	Name	Description
DRUG	Plinabulin	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).
DRUG	Pegfilgrastim	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.
DRUG	Docetaxel, doxorubicin, and cyclophosphamide (TAC)	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.

Timeline

• Start date: 2017-11-27
• Primary completion: 2018-10-15
• Completion: 2019-01-03
• First posted: 2020-01-14
• Last updated: 2020-01-18

Locations

11 sites across 2 countries: China, Ukraine

Regulatory

• FDA-regulated drug study