Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Blood and Lymph Conditions

Rare Diseases

Breast Neoplasms

Pain

Neutropenia

Agranulocytosis

Leukopenia

Cytopenia

Hematologic Diseases

Leukocyte Disorders

Granulocytopenia

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Anti-Inflammatory Agents

Anti-Infective Agents

Docetaxel

Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

Triamcinolone

Triamcinolone Acetonide

Triamcinolone hexacetonide

Triamcinolone diacetate

Lenograstim

Taxane

Alkylating Agents

Diketopiperazines

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Tubulin Modulators

Antimitotic Agents

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Phase 3:TAC + Pegfilgrastim (6 mg)+ D5W placebo

D5W Placebo: 250 ml D5W to match the administration of plinabulin diluted in 250 ml D5W

Phase 3: TAC+ Plinabulin (40 mg) + Pegfilgrastim (6 mg)

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.

Pegfilgrastim

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).

Plinabulin

Placebo 250 ml D5W to match the administration of plinabulin diluted in 250 ml D5W

D5W Placebo

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.

Docetaxel, doxorubicin, and cyclophosphamide (TAC)

Douglas Blayney, M.D.

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.

Plinabulin is masked using a double-dummy design. Docetaxel/Doxorubicin/Cyclophasphamide administration is not masked.

Plinabulin vs. Pegfilgrastim in Prevention of TAC Induced Neutropenia

A Phase 3, Randomized Study to Evaluate Plinabulin Versus Pegfilgrastim in the Prevention of Severe Neutropenia in Breast Cancer Patients Receiving Myelosuppressive Chemotherapy With Docetaxel, Doxorubicin, and Cyclophosphamide (TAC) (Protective 2)

DSN is defined as Days of Grade 4 Neutropenia (ANC less than 0.5 X 109/L)

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.

To evaluate the effect of Plinabulin related to DSN within 15 days

Record the bone pain score from the numerical rating scale (NRS)

Composite risks includes infection, FN, hospitalization, significant disability, life threatening and death

Assess the percentage of patients with RDI \< 85%

BeyondSpring Pharmaceuticals Inc.

Pharmaceutical Solutions

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.

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.

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).

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)

Days with Severe Neutropenia in treatment Cycle 1

Frequency of patients with at least 1 day of Grade 4 neutropenia (ANC \<0.5 × 109/L)

Mean pain score from the patient bone pain scale from pre-dose Day 1 to Day 8 in Cycle 1 (0-10 scale, higher score means worse outcome)

Change in bone pain score from pre-dose Day 1 through Day 8 in Cycle1 (0-10 scale, higher score means worse outcome)

Incidences, occurrences, and severity of AEs/SAEs Cycle 1-4

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Plinabulin vs. Pegfilgrastim in Prevention of TAC Induced Neutropenia	NCT03294577	Chemotherapy-in...	Pegfilgrastim Plinabulin D5W Placebo Docetaxel, doxo...	18 Years -	BeyondSpring Pharmaceuticals Inc.
Plinabulin iv Solution in Prevention of TAC Induced Neutropenia	NCT04227990	Chemotherapy-in...	Plinabulin Pegfilgrastim Docetaxel, doxo...	18 Years -	BeyondSpring Pharmaceuticals Inc.
Plinabulin iv Solution in Prevention of TAC Induced Neutropenia	NCT04227990	Chemotherapy-in...	Plinabulin Pegfilgrastim Docetaxel, doxo...	18 Years -	BeyondSpring Pharmaceuticals Inc.

Spots Global Cancer Trial Database for docetaxel, doxorubicin, and cyclophosphamide (tac)