Plinabulin vs. Pegfilgrastim in Prevention of TAC Induced Neutropenia

NCT03294577 | Unknown Phase 3 DMC FDA Drug

• 1 other identifier: BPI-2358-106 phase 3
• Study Type: interventional
• Target: 221
• Locations: 2 countries
• Sites: 20

Brief Summary

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.

Conditions

Chemotherapy-induced Neutropenia

Keywords

Plinabulin; Pegfilgrastim; Chemotherapy induced neutropenia; bone pain

Outcome Measures

Primary Outcomes (1)

• 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)

  Duration of Grade 4 neutropenia assessed during the first cycle (21 days)

Secondary Outcomes (7)

• Mean DSN assessment

  From day 1 to day 8 in first cycle (21 days)

• Mean ANC nadir

  Duration of first cycle (21 days)

• Percentage of Patients without grade 3 and grade 4 neutropenia

  Duration of first cycle (21 days)

• Mean DSN assessment within 15 days

  From day 1 to day 15 in the first cycle (21 days)

• Average change in bone pain

  From -1 day over the observational period

Study Arms (2)

TAC + Pegfilgrastim

ACTIVE COMPARATOR

Phase 3:TAC + Pegfilgrastim (6 mg)+ D5W placebo D5W Placebo: 250 ml D5W to match the administration of plinabulin diluted in 250 ml D5W

Drug: Pegfilgrastim; Other: D5W Placebo; Drug: Docetaxel, doxorubicin, and cyclophosphamide (TAC)

TAC + Pegfilgrastim + Plinabulin

EXPERIMENTAL

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

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

Interventions

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, G-CSF

TAC + Pegfilgrastim

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).

Also known as: BPI-2358, NPI-2358

TAC + Pegfilgrastim + Plinabulin

D5W Placebo OTHER

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

TAC + Pegfilgrastim

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.

Also known as: Taxotere, Adriamycin, Cytoxan

TAC + Pegfilgrastim; TAC + Pegfilgrastim + Plinabulin

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• 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, \& 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
• 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.
• Laboratory results provided by the central laboratory within 14 days prior to study drug administration within noted ranges, per study protocol (local laboratories may be accepted on a case by case basis after discussion with the medical monitor; however in this case central laboratories must also be taken within the screening time window)
• 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.

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 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

Sponsors & Collaborators

• BeyondSpring Pharmaceuticals Inc.: lead

Study Sites (20)

No. 1 Banshandong Road

Hangzhou, Gongshu District, China

Location

Cancer Center of Guangzhou Medical University

Guangzhou, Guangdong, China

Location

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, Ukraine

Location

Regional Clinical Oncology Center

Kharkiv, Ukraine

Location

V.T. Zaycev Institute

Kharkiv, Ukraine

Location

Kirovograd Regional Oncological Center

Kropyvnytskyi, 25011, Ukraine

Location

Public Institution Kryvyi Rih Oncology Center

Krutyi Bereh, 50048, Ukraine

Location

Hemotherapy Department

Kyiv, Ukraine

Location

Kyiv City Clinical Oncological Center

Kyiv, Ukraine

Location

Lviv State Oncological Regional

Lviv, Ukraine

Location

Odessa regional clinical hospital Thoracic Surgery Department Academician Zabolotnoho

Odesa, 65025, Ukraine

Location

Zakarpattia Regional Clinical Oncology Center

Uzhhorod, Ukraine

Location

Vinnytsya Regional Clinical Oncology Dispensary

Vinnytsia, Ukraine

Location

Zaporizhia Regional Clinical Oncology Dispensary

Zaporizhzhya, Ukraine

Location

MeSH Terms

Interventions

pegfilgrastim; Granulocyte Colony-Stimulating Factor; NPI 2358; Docetaxel; Doxorubicin; Cyclophosphamide

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Aminoglycosides; Glycosides; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds

Study Officials

• Douglas Blayney, M.D.

  Stanford University School of Medicine - Cancer Institute

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Plinabulin is masked using a double-dummy design. Docetaxel/Doxorubicin/Cyclophasphamide administration is not masked.
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 22, 2017
• First Posted: September 27, 2017
• Study Start: October 23, 2019
• Primary Completion: September 25, 2020
• Study Completion: September 25, 2025
• Last Updated: January 15, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

UA (13); CN (7)