Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Plinabulin vs. Pegfilgrastim in Prevention of TAC Induced Neutropenia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03294577
Recruitment Status : Recruiting
First Posted : September 27, 2017
Last Update Posted : May 8, 2020
Sponsor:
Information provided by (Responsible Party):
BeyondSpring Pharmaceuticals Inc.

Tracking Information
First Submitted Date  ICMJE September 22, 2017
First Posted Date  ICMJE September 27, 2017
Last Update Posted Date May 8, 2020
Actual Study Start Date  ICMJE December 1, 2019
Estimated Primary Completion Date June 15, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 6, 2020)
Percentage of patients with Duration of Severe Neutropenia (DSN) =0 [ Time Frame: Duration of Grade 4 neutropenia assessed during the first cycle (21 days) ]
DSN is defined as Days of Grade 4 Neutropenia (ANC less than 0.5 X 109/L)
Original Primary Outcome Measures  ICMJE
 (submitted: September 26, 2017)
Duration of Severe Neutropenia (DSN) [ Time Frame: Duration of Grade 4 neutropenia assessed once within the first 21-day cycle ]
Duration of Grade 4 Neutropenia (ANC less than 0.5 X 109/L)
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 6, 2020)
  • Mean DSN assessment [ Time Frame: From day 1 to day 8 in first cycle (21 days) ]
    DSN is defined as Days of Grade 4 Neutropenia (ANC less than 0.5 X 109/L)
  • Mean ANC nadir [ Time Frame: Duration of first cycle (21 days) ]
    record and evaluate the lowest ANC value
  • Percentage of Patients without grade 3 and grade 4 neutropenia [ Time Frame: Duration of first cycle (21 days) ]
    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.
  • Mean DSN assessment within 15 days [ Time Frame: From day 1 to day 15 in the first cycle (21 days) ]
    To evaluate the effect of Plinabulin related to DSN within 15 days
  • Average change in bone pain [ Time Frame: From -1 day over the observational period ]
    Record the bone pain score from the numerical rating scale (NRS)
  • Rate of composite risks [ Time Frame: Duration of all 4 cycle (21 days) ]
    Composite risks includes infection, FN, hospitalization, significant disability, life threatening and death
  • Percentage of patients with relative dose intensity < 85% [ Time Frame: Duration of all 4 cycle (21 days) ]
    Assess the percentage of patients with RDI < 85%
Original Secondary Outcome Measures  ICMJE
 (submitted: September 26, 2017)
  • Bone Pain [ Time Frame: Duration of the study treatment period (approximately 4 cycles of 21 days each) ]
    Bone pain inventory - Short Form
  • Incidence of Grade 4 neutropenia [ Time Frame: Duration of the 21 day, cycle 1 ]
    Grade 4 neutropenia (ANC less than 0.5 x 109/L)
  • Incidence of Febrile Neutropenia (FN) [ Time Frame: Duration of the study treatment period (approximately 4 cycles of 21 days each) ]
    FN = ANC less than 0.5 x 109/L and body temperature ≥ 38.3°C
  • Incidence of documented infections [ Time Frame: Duration of the study treatment period (approximately 4 cycles of 21 days each) ]
    Percentage of patients in with documented infections
  • Incidence of hospitalizations due to FN [ Time Frame: Duration of the study treatment period (approximately 4 cycles of 21 days each) ]
    FN = ANC less than 0.5 x 109/L and body temperature ≥ 38.3°C
  • Duration of hospitalizations due to FN [ Time Frame: Duration of the study treatment period (approximately 4 cycles of 21 days each) ]
    FN = ANC less than 0.5 x 109/L and body temperature ≥ 38.3°C
  • Incidence of use of pegfilgrastim or filgrastim as treatment for neutropenia [ Time Frame: Duration of the study treatment period (approximately 4 cycles of 21 days each) ]
    FN = ANC less than 0.5 × 109/L and body temperature ≥ 38.3°C
  • Incidence of antibiotic use [ Time Frame: Duration of the study treatment period (approximately 4 cycles of 21 days each) ]
    Frequency of antibiotic use
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Plinabulin vs. Pegfilgrastim in Prevention of TAC Induced Neutropenia
Official Title  ICMJE 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)
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.

Detailed Description

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).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description:
Plinabulin is masked using a double-dummy design. Docetaxel/Doxorubicin/Cyclophasphamide administration is not masked.
Primary Purpose: Supportive Care
Condition  ICMJE Chemotherapy-induced Neutropenia
Intervention  ICMJE
  • 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.
    Other Names:
    • Neulasta
    • G-CSF
  • 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).
    Other Names:
    • BPI-2358
    • NPI-2358
  • Other: D5W Placebo
    Placebo 250 ml D5W to match the administration of plinabulin diluted in 250 ml D5W
  • 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.
    Other Names:
    • Taxotere
    • Adriamycin
    • Cytoxan
Study Arms  ICMJE
  • Active Comparator: TAC + Pegfilgrastim

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

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

    Interventions:
    • Drug: Pegfilgrastim
    • Other: D5W Placebo
    • Drug: Docetaxel, doxorubicin, and cyclophosphamide (TAC)
  • Experimental: TAC + Pegfilgrastim + Plinabulin
    Phase 3: TAC+ Plinabulin (40 mg) + Pegfilgrastim (6 mg)
    Interventions:
    • Drug: Plinabulin
    • Drug: Docetaxel, doxorubicin, and cyclophosphamide (TAC)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 20, 2019)
222
Original Estimated Enrollment  ICMJE
 (submitted: September 26, 2017)
180
Estimated Study Completion Date  ICMJE July 15, 2020
Estimated Primary Completion Date June 15, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Women who are at least 18 years of age at the time of signing the informed consent form.
  2. In the opinion of their treating oncology investigator, are candidates for at least 4 cycles of chemotherapy with TAC (docetaxel, doxorubicin, & cyclophosphamide).
  3. 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.
  4. Pathological confirmation of cancer is required.
  5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  6. Have life expectancy of 3 months or more.
  7. 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)
  8. Prothrombin time (PT) and International Normalized Ratio (INR) ≤1.5 × ULN, activated partial thromboplastin time (PTT) ≤1.5 × ULN, based on central laboratory results.
  9. Women of childbearing potential have a negative pregnancy test at screening.

Exclusion Criteria:

  1. History of myelogenous leukemia, myelodysplastic syndrome, or sickle cell disease.
  2. 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.
  3. 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).
  4. Receiving any concurrent anticancer therapies (including concomitant anti-HER2/neu agents such as trastuzumab [Herceptin®], trastuzumab emtansine [TDM 1, Kadcyla®], pertuzumab [Perjeta®], lapatinib [Tykerb®]).
  5. Received a prior bone marrow or stem cell transplant.
  6. Have a co-existing active infection or received systemic anti-infective treatment within 72 hours before the first dose of study drug.
  7. Concurrent or prior radiation therapy within 4 weeks before the first dose of study drug.
  8. Chronic use of filgrastim, pegfilgrastim, or any bioequivalent (biosimilar) for severe chronic neutropenia or other chronic neutropenia syndrome.
  9. 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.
  10. 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
  11. 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.
  12. Any other active malignancy requiring active therapy.
  13. Known human immunodeficiency virus (HIV) seropositivity.
  14. Active Hepatitis B virus (HBV) infection which requires antiviral treatment or the patient has detectable Hepatitis B surface Antigen (HBsAg); hepatitis B surface antibody (anti-HBs) without detectable HBsAg does not exclude patients from the study. Hepatitis C infection (Hepatitis C antibody reactive) which requires treatment also excludes patients from the study.
  15. Female patient who is pregnant or lactating.
  16. Use of prophylactic antibiotics.
  17. Unwilling or unable to comply with procedures required in this protocol.
  18. History of allergy to any of the study drugs.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Ramon Mohanlal, M.D., Ph.D. 917-526- 1956 rmohanlal@beyondspringpharma.com
Contact: Ilda Boholli, M.P.H iboholli@beyondspringpharma.com
Listed Location Countries  ICMJE China,   Ukraine
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03294577
Other Study ID Numbers  ICMJE BPI-2358-106 phase 3
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party BeyondSpring Pharmaceuticals Inc.
Study Sponsor  ICMJE BeyondSpring Pharmaceuticals Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Douglas Blayney, M.D. Stanford University School of Medicine - Cancer Institute
PRS Account BeyondSpring Pharmaceuticals Inc.
Verification Date May 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP