Plinabulin iv Solution in Prevention of TAC Induced Neutropenia

NCT04227990 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: BPI-2358-106 Phase 2
• Study Type: interventional
• Target: 115
• Locations: 2 countries
• Sites: 11

Brief 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.

Conditions

Chemotherapy-induced Neutropenia

Outcome Measures

Primary Outcomes (1)

• Duration of Severe Neutropenia (DSN)

  Days with Severe Neutropenia in treatment Cycle 1

  Cycle 1 (21 days)

Secondary Outcomes (4)

• Frequency of Grade 4 neutropenia

  Cycle 1 (21 days)

• Bone pain score

  Cycle 1 (21 days)

• Change in bone pain score

  Cycle 1 (21 days)

• Adverse events

  Cycle 1 - 4 (21-day cycle)

Study Arms (7)

TAC + Pegfilgrastim (6 mg)

ACTIVE COMPARATOR

Drug: Pegfilgrastim; Drug: Docetaxel, doxorubicin, and cyclophosphamide (TAC)

TAC + Plinabulin 10 mg/m^2

EXPERIMENTAL

Drug: Plinabulin; Drug: Docetaxel, doxorubicin, and cyclophosphamide (TAC)

TAC + Plinabulin 20 mg/m^2

EXPERIMENTAL

Drug: Plinabulin; Drug: Docetaxel, doxorubicin, and cyclophosphamide (TAC)

TAC + Plinabulin 30 mg/m^2

EXPERIMENTAL

Drug: Plinabulin; Drug: Docetaxel, doxorubicin, and cyclophosphamide (TAC)

TAC + Pegfilgrastim (1.5 mg) + Plinabulin (20 mg/m^2)

EXPERIMENTAL

Drug: Plinabulin; Drug: Pegfilgrastim; Drug: Docetaxel, doxorubicin, and cyclophosphamide (TAC)

TAC + Pegfilgrastim (3 mg) + Plinabulin (20 mg/m^2)

EXPERIMENTAL

Drug: Plinabulin; Drug: Pegfilgrastim; Drug: Docetaxel, doxorubicin, and cyclophosphamide (TAC)

TAC + Pegfilgrastim (6 mg) + Plinabulin (20 mg/m^2)

EXPERIMENTAL

Drug: Plinabulin; Drug: Pegfilgrastim; Drug: Docetaxel, doxorubicin, and cyclophosphamide (TAC)

Interventions

Plinabulin DRUG

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).

TAC + Pegfilgrastim (1.5 mg) + Plinabulin (20 mg/m^2); TAC + Pegfilgrastim (3 mg) + Plinabulin (20 mg/m^2); TAC + Pegfilgrastim (6 mg) + Plinabulin (20 mg/m^2); TAC + Plinabulin 10 mg/m^2; TAC + Plinabulin 20 mg/m^2; TAC + Plinabulin 30 mg/m^2

Pegfilgrastim DRUG

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.

Also known as: Neulasta

TAC + Pegfilgrastim (1.5 mg) + Plinabulin (20 mg/m^2); TAC + Pegfilgrastim (3 mg) + Plinabulin (20 mg/m^2); TAC + Pegfilgrastim (6 mg); TAC + Pegfilgrastim (6 mg) + Plinabulin (20 mg/m^2)

Docetaxel, doxorubicin, and cyclophosphamide (TAC) DRUG

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.

TAC + Pegfilgrastim (1.5 mg) + Plinabulin (20 mg/m^2); TAC + Pegfilgrastim (3 mg) + Plinabulin (20 mg/m^2); TAC + Pegfilgrastim (6 mg); TAC + Pegfilgrastim (6 mg) + Plinabulin (20 mg/m^2); TAC + Plinabulin 10 mg/m^2; TAC + Plinabulin 20 mg/m^2; TAC + Plinabulin 30 mg/m^2

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Women who are at least 18 years of age at the time of signing the informed consent form.
• In the opinion of their treating oncology investigator, are candidates for at least 4 cycles of chemotherapy with TAC (docetaxel, doxorubicin, and cyclophosphamide).
• Patients who are candidates for adjuvant or neoadjuvant TAC will meet all of the following criteria:
• Biopsy proven, early stage (Stage I and II) and Stage III breast cancer, and Are within 60 days of a diagnostic or surgical procedure (biopsy, umpectomy, mastectomy), and Have had no prior chemotherapy.
• Pathological confirmation of cancer is required.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Have life expectancy of 3 months or more.
• The following laboratory results provided by the central laboratory within 14 days prior to study drug administration:
• ANC ≥ 1.5 x 10\^9/L independent of growth factor support; hemoglobin ≥ 9 g/dL independent of transfusion or growth factor support; calculated creatinine clearance (CLcr) ≥ 60 mL/min using Cockcroft-Gault formula; Serum total bilirubin ≤ upper limit of normal (ULN); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) as 2.5 x ULN (≤ 1.5 x ULN if alkaline phosphate is \> 2.5 x ULN).
• Prothrombin time (PT) and International Normalized Ratio (INR) ≤1.5 × ULN, activated partial thromboplastin time (PTT) ≤1.5 × ULN, based on central laboratory results.
• Women of childbearing potential have a negative pregnancy test at screening. Women of childbearing potential are defined as sexually mature women without prior hysterectomy or who have had any evidence of menses in the past 12 months. However, women who have been amenorrhoeic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, anti-estrogens, or ovarian suppression.
• Women of childbearing potential (i.e., menstruating women) must have a negative urine pregnancy test (positive urine tests are to be confirmed by serum test) documented within the 24-hour period prior to the first dose of study drug.
• Sexually active women of childbearing potential enrolled in the study must agree to use two forms of accepted methods of contraception during the course of the study and for 3 months after their last dose of study drug. Effective birth control includes (a) intrauterine device plus one barrier method; (b) on stable doses of hormonal contraception for at least 3 months (e.g., oral, injectable, implant, transdermal) plus one barrier method; (c) 2 barrier methods. Effective barrier methods are male or female condoms, diaphragms, and spermicides (creams or gels that contain a chemical to kill sperm); or (d) a vasectomized partner.

You may not qualify if:

• History of myelogenous leukemia, myelodysplastic syndrome, or sickle cell disease.
• Use of strong CYP3A4, CYP2D6 or P-glycoprotein (P-gp) inhibitors and inducers, within 14 days of the first administration of study drug and for the duration of the study.
• Received an investigational agent or tumor vaccine within 2 weeks before the first dose of study drug; patients must have recovered from toxicity of prior treatment and have no \>Grade 1 Common Terminology Criteria for Adverse Events (CTCAE) (v4.03) treatment emergent adverse events (TEAE).
• Receiving any concurrent anticancer therapies (including concomitant anti-HER2/neu agents such as trastuzumab \[Herceptin\], trastuzumab emtansine \[TDM-1, Kadcyla®\], pertuzumab \[Perjeta®\], lapatinib \[Tykerb®\]).
• Received a prior bone marrow or stem cell transplant.
• Have a co-existing active infection or received systemic anti-infective treatment within 72 hours before the first dose of study drug.
• Concurrent or prior radiation therapy within 4 weeks before the first dose of study drug.
• Chronic use of filgrastim, pegfilgrastim, or any bioequivalent (biosimilar) for severe chronic neutropenia or other chronic neutropenia syndrome.
• Presence of any serious or uncontrolled illness including, but not limited to: uncontrolled diabetes, ongoing or active infection, symptomatic congestive heart failure unstable angina pectoris, uncontrolled cardiac arrhythmia, uncontrolled arterial thrombosis, symptomatic pulmonary embolism, and psychiatric illness that would limit compliance with study requirements or any other conditions that would preclude the patient from study treatment as per the discretion of the Investigator.
• Significant prior doxorubicin (\>240 mg/m2) or anthracycline exposure that would preclude the safe administration of TAC chemotherapy as described in the protocol.
• Significant cardiovascular history:
• Cardiac ventricular dysfunction inhibiting the patient"s ability to receive 4 cycles of doxorubicin.
• History of myocardial infarction or ischemic heart disease within 1 year (within a window of up to 18 days less than 1 year) before first study drug administration Uncontrolled arrhythmia History of congenital QT prolongation Electrocardiogram (ECG) findings consistent with active ischemic heart disease New York Heart Association Class III or IV cardiac disease; Uncontrolled hypertension: blood pressure consistently \>150 mm Hg systolic and \> 100 mm Hg diastolic in spite of antihypertensive medication
• History of hemorrhagic diarrhea, inflammatory bowel disease, or active uncontrolled peptic ulcer disease. (Concomitant therapy with ranitidine or its equivalent and/or omeprazole or its equivalent is acceptable). History of ileus or other significant gastrointestinal disorder known to predispose to ileus or chronic bowel hypomotility.
• Any other active malignancy requiring active therapy.

Sponsors & Collaborators

• BeyondSpring Pharmaceuticals Inc.: lead

Study Sites (11)

Cancer Center of Guangzhou Medical University Breast Oncology

Guangzhou, Guangzhou, 510000, China

Location

Harbin Medical University Cancer Hospital

Harbin, Harbin, 150000, China

Location

Fourth Hospital of Hebei Medical University Breast cancer department

Shijiazhuang, Hebei, 500000, China

Location

China-Japan Union Hospital of Jilin University Tumor department of Hematology

Changchun, Jilin, 130000, China

Location

Liaoning Cancer Hospital & Institute

Shenyang, Shenyang, 110000, China

Location

Dnipropetrovsk City Multifunctional Hospital #4 Oncology Department

Dnipro, 49102, Ukraine

Location

Prykarpatskiy Regional Oncological Center

Ivano-Frankivsk, 76000, Ukraine

Location

"V.T. Zaycev Institute of General and Urgent Surgery NAMS of Ukraine Dept. of Oncology

Kharkiv, 61103, Ukraine

Location

Kirovograd Regional Oncological Center

Kropyvnytskyi, 25011, Ukraine

Location

Public Institution Kryvyi Rih Oncology Center

Krutyi Bereh, 50048, Ukraine

Location

Odessa regional clinical hospital Thoracic Surgery Department Academician Zabolotnoho

Odesa, 65025, Ukraine

Location

MeSH Terms

Interventions

NPI 2358; pegfilgrastim; Docetaxel; Doxorubicin; Cyclophosphamide

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 10, 2020
• First Posted: January 14, 2020
• Study Start: November 27, 2017
• Primary Completion: October 15, 2018
• Study Completion: January 3, 2019
• Last Updated: January 18, 2020

Record last verified: 2020-01

Locations

CN (5); UA (6)