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

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ClinicalTrials.gov Identifier: NCT03294577
Recruitment Status : Recruiting
First Posted : September 27, 2017
Last Update Posted : October 11, 2018
Sponsor:
Information provided by (Responsible Party):
BeyondSpring Pharmaceuticals Inc.

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.


Condition or disease Intervention/treatment Phase
Chemotherapy-induced Neutropenia Drug: Pegfilgrastim Drug: Plinabulin Other: D5W Placebo Other: Saline Placebo Drug: Docetaxel, doxorubicin, and cyclophosphamide (TAC) Phase 2 Phase 3

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 237 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: During Phase 3 Only: Plinabulin and pegfilgrastim are each masked using a double-dummy design. Docetaxel/Doxorubicin/Cyclophasphamide administration is not masked.
Primary Purpose: Supportive Care
Official Title: A Phase 2/3, Multicenter, Randomized Study to Evaluate Plinabulin Versus Pegfilgrastim in Reducing the Duration of Severe Neutropenia in Breast Cancer Patients Receiving Myelosuppressive Chemotherapy With Docetaxel, Doxorubicin, and Cyclophosphamide (TAC) (Protective 2)
Actual Study Start Date : November 27, 2017
Estimated Primary Completion Date : October 1, 2018
Estimated Study Completion Date : April 18, 2019


Arm Intervention/treatment
Active Comparator: Pegfilgrastim (6 mg)
Phase 2: TAC + Pegfilgrastim (6 mg)
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: 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

Experimental: Plinabulin (10 mg/m^2)
Phase 2: TAC + Plinabulin (10 mg/m^2)
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

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

Experimental: Plinabulin (20 mg/m^2)
Phase 2: TAC + Plinabulin (20 mg/m^2)
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

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

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

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

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

Experimental: Plinabulin (PR3D)

Phase 3: TAC+ Plinabulin + saline placebo

Saline Placebo: Placebo Syringe 0.6 ml Saline to match the 0.6 ml pegfilgrastim administration

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: Saline Placebo
Placebo Syringe 0.6 ml Saline to match the 0.6 ml pegfilgrastim administration

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

Experimental: Plinabulin (30 mg/m^2)
Phase 2: TAC + Plinabulin (30 mg/m^2)
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

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

Experimental: Plinabulin20 mg+pegfilgrastim1.5mg
Phase 2: TAC + Plinabulin (20 mg/m^2) + pegfilgrastim (1.5 mg)
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

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

Experimental: Plinabulin20 mg+pegfilgrastim 3mg
Phase 2: TAC + Plinabulin (20 mg/m^2) + pegfilgrastim (3.0 mg)
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

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

Experimental: Plinabulin20 mg+pegfilgrastim 6mg
Phase 2: TAC + Plinabulin (20 mg/m^2) + pegfilgrastim (6.0 mg)
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

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




Primary Outcome Measures :
  1. Duration of Severe Neutropenia (DSN) [ Time Frame: Duration of Grade 4 neutropenia assessed during the first 21-day cycle ]
    Duration of Grade 4 Neutropenia (ANC less than 0.5 X 109/L)


Secondary Outcome Measures :
  1. Bone Pain [ Time Frame: Duration of the study treatment period (approximately 4 cycles of 21 days each) ]
    Bone pain Scale

  2. 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)

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. Incidence of antibiotic use [ Time Frame: Duration of the study treatment period (approximately 4 cycles of 21 days each) ]
    Frequency of antibiotic use



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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 prior doxorubicin (>240 mg/m2) or anthracycline exposure that would preclude the safe administration of TAC chemotherapy as described in the protocol.
  11. 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
  12. 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.
  13. Any other active malignancy requiring active therapy.
  14. Known human immunodeficiency virus (HIV) seropositivity.
  15. 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.
  16. Female patient who is pregnant or lactating.
  17. Use of prophylactic antibiotics.
  18. Unwilling or unable to comply with procedures required in this protocol.
  19. History of allergy to any of the study drugs.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03294577


Contacts
Contact: Ramon Mohanlal, M.D., Ph.D. 917-526-1956 rmohanlal@beyondspringpharma.com
Contact: Ilda Boholli, M.P.H 973-919-4410 iboholli@beyondspringpharma.com

Locations
China, Guangzhou
Cancer Center of Guangzhou Medical University Breast Oncology Recruiting
Guangzhou, Guangzhou, China, 510000
Contact: Hongsheng Li, MD         
China, Harbin
Harbin Medical University Cancer Hospital Recruiting
Harbin, Harbin, China, 150000
Contact: Qingyuan Zhang, MD         
China, Shenyang
Liaoning Cancer Hospital & Institute Recruiting
Shenyang, Shenyang, China, 110000
Contact: Tao Sun, MD         
Sponsors and Collaborators
BeyondSpring Pharmaceuticals Inc.
Investigators
Study Chair: Douglas Blayney, M.D. Stanford University School of Medicine - Cancer Institute

Responsible Party: BeyondSpring Pharmaceuticals Inc.
ClinicalTrials.gov Identifier: NCT03294577     History of Changes
Other Study ID Numbers: BPI-2358-106
First Posted: September 27, 2017    Key Record Dates
Last Update Posted: October 11, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by BeyondSpring Pharmaceuticals Inc.:
Plinabulin
Pegfilgrastim
bone pain
Chemotherapy induced neutropenia

Additional relevant MeSH terms:
Neutropenia
Agranulocytosis
Leukopenia
Leukocyte Disorders
Hematologic Diseases
Cyclophosphamide
Docetaxel
Liposomal doxorubicin
Doxorubicin
Diketopiperazines
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Anti-Bacterial Agents
Anti-Infective Agents