ClinicalTrials.gov
ClinicalTrials.gov Menu

Plinabulin vs. Pegfilgrastim in Patients With Solid Tumors Receiving Docetaxel Myelosuppressive Chemotherapy (Protective-1)

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: NCT03102606
Recruitment Status : Recruiting
First Posted : April 6, 2017
Last Update Posted : April 6, 2017
Sponsor:
Collaborators:
Chiltern International Inc.
ICON plc
Information provided by (Responsible Party):
BeyondSpring Pharmaceuticals Inc.

Brief Summary:
To assess Duration of Severe Neutropenia (DSN) in treatment Cycle 1 in patients with advanced or metastatic breast cancer, who have failed >/= 1 but < 5 prior lines of chemotherapy; advanced or metastatic non-small cell lung cancer (NSCLC) after failing platinum based therapy; or hormone refractory (androgen independent) metastatic prostate cancer treated with docetaxel (75 mg/m2) + plinabulin (RP3D) versus docetaxel (75 mg/m2) + pegfilgrastim (6 mg). Neutrophils count will be assessed at baseline; Pre dose during Cycle 1, Day 1, 2, 5, 6, 7, 8, 9, 10, 15.

Condition or disease Intervention/treatment Phase
Chemotherapy-induced Neutropenia Drug: Plinabulin Drug: Pegfilgrastim Other: Saline Placebo Other: D5W Placebo Phase 2 Phase 3

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 170 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: Plinabulin and pegfilgrastim are each masked using a double-dummy design. Docetaxel administration is not masked.
Primary Purpose: Supportive Care
Official Title: A Phase 2/3, Multicenter, Randomized, Double Blind, Study to Evaluate Duration of Severe Neutropenia With Plinabulin Versus Pegfilgrastim in Patients With Solid Tumors Receiving Docetaxel Myelosuppressive Chemotherapy (Protective 1)
Actual Study Start Date : March 13, 2017
Estimated Primary Completion Date : March 15, 2018
Estimated Study Completion Date : June 15, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 20 mg/m2 Plinabulin + saline placebo
20 mg/m2 Plinabulin and 0.6 ml saline matching pegfilgrastim syringe
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

Experimental: 10 mg/m2 Plinabulin + saline placebo
10 mg/m2 Plinabulin and 0.6 ml saline matching pegfilgrastim syringe
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

Experimental: 5 mg/m2 Plinabulin + saline placebo
5 mg/m2 Plinabulin and 0.6 ml saline matching pegfilgrastim syringe
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

Active Comparator: 0.6 ml Pegfilgrastim + D5W placebo
0.6 ml Pegfilgrastim and 250 ml D5W matching plinabulin dilution
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




Primary Outcome Measures :
  1. 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 < 0.5 × 109/L)


Secondary Outcome Measures :
  1. Incidence of Grade 4 neutropenia [ Time Frame: Duration of the study treatment period (84 days) ]
    Grade 4 neutropenia (ANC < 0.5 × 109/L)

  2. Incidence of Febrile Neutropenia (FN) [ Time Frame: Duration of the study treatment period (84 days) ]
    FN = ANC < 0.5 × 10**9/L and body temperature ≥ 38.3°C

  3. Health-related QoL questionnaire evaluated with EORTC QLQ-C30 [ Time Frame: Duration of the study treatment period (84 days) ]
    Quality of Life Measurement

  4. Neutrophil Nadir [ Time Frame: The neutrophil nadir is identified once during the first 21-day cycle ]
    Minimum neutrophil count during Cycle 1

  5. Incidence of docetaxel treatment modification [ Time Frame: Duration of the study treatment period (84) days ]
    Modification of docetaxel administration

  6. Bone pain [ Time Frame: Duration of the study treatment period (84 days) ]
    Bone pain inventory - Short Form

  7. Incidence of Hospitalizations due to FN [ Time Frame: Duration of the study treatment period (84 days) ]
    FN = ANC < 0.5 × 10**9/L and body temperature ≥ 38.3°C

  8. Incidence of documented infections [ Time Frame: Duration of the study treatment period (84 days) ]
    Percentage of patients in with documented infections



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:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. At least ≥ 18 years of age (male or female) at the time of signing the informed consent form.
  2. ECOG performance status of 0 to 1.
  3. Patients with:

    Phase 2 only:

    • Advanced or metastatic NSCLC failing platinum based therapy

    Phase 3 only:

    • Advanced or metastatic breast cancer, who have failed </= 1 but < 5 prior lines of chemotherapy
    • Advanced or metastatic NSCLC failing platinum based therapy
    • Hormone refractory (androgen independent) metastatic prostate cancer (HRPC).
  4. Pathology confirmation of cancer is required.
  5. Patients with ≥ 1 of the following risk factors, at the initiation of docetaxel chemotherapy, that would require neutropenia prophylaxis per National Comprehensive Cancer Network (NCCN) guidelines (version 2, 2016) Myeloid Growth Factors (refer to Appendix C):

    • Prior chemotherapy or radiation treatment
    • Bone marrow involvement by tumor
    • Surgery and/or open wounds within 4 weeks of first administration of study drug
    • Age > 65 years of age and receiving full chemotherapy dose intensity
  6. Life expectancy of 3 months or more.
  7. The following laboratory results provided by the central laboratory within 14 days prior to study drug administration:

    • Hemoglobin >/= 9 g/dL independent of transfusion or growth factor support
    • Absolute neutrophil count >/= 1.5 x 10**9/L independent of growth factor support
    • Serum total bilirubin </= 1.5 times the upper limit normal (ULN), unless the patient has a diagnosis of Gilbert's disease in which case direct bilirubin < t 1.5 times ULN of the direct bilirubin. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) </= 2.5 x ULN (</= 1.5 x ULN if alkaline phosphatase is > 2.5 x ULN)
    • Serum creatinine </= 1.5 x ULN
  8. Prothrombin time (PT)/International Normalized Ratio (INR) ≤ 1.5 × upper limit of normal (ULN), activated partial thromboplastin time (PTT) ≤ 1.5 × ULN, based on central laboratory results.
  9. Female subjects of childbearing potential have a negative pregnancy test at screening. Females 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 (IUD) 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.
    • For male patients who are sexually active and who are partners of premenopausal women: agreement to use two forms of contraception during the treatment period and for at least 3 months after the last dose of study drug.

Exclusion Criteria:

  1. History of myelogenous leukemia, myelodysplastic syndrome or concomitant sickle cell disease.
  2. Received chemotherapy within 4 weeks prior to the first dose of study drug.
  3. Received prior docetaxel treatment, except if docetaxel received as adjuvant therapy for breast cancer > 1 year before the first dose of study drug.
  4. Received no prior chemotherapy or >/= 5 lines of cytotoxic chemotherapy for advanced or metastatic breast cancer (adjuvant chemotherapy will count as one line of chemotherapy, and any hormonal or biological, non conjugate therapy [e.g., trastuzumab] will not count as a line of therapy).
  5. Current use of strong cytochrome P450 (CYP) 3A4 inhibitors, within 3 days of the first administration of study drug, and 7 days after treatment with taxanes OR requires use of strong CYP3A4 inhibitors (refer to Section 11.6.2)
  6. 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 treatment emergent AEs.
  7. Receiving any concurrent anticancer therapies.
  8. Received a prior bone marrow or stem cell transplant.
  9. Has a co-existing active infection or received systemic anti-infective treatment within 72 hours before the first dose of study drug.
  10. Prior radiation therapy within the 4 weeks before the first dose of study drug.
  11. Prior use of pegfilgrastim or filgrastim within 4 weeks before the first dose of study drug.
  12. 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, or 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.
  13. Significant cardiovascular history:

    • History of myocardial infarction or ischemic heart disease within 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.
  14. 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.
  15. Any other malignancy requiring active therapy.
  16. Known human immunodeficiency virus (HIV) seropositivity.
  17. Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection requiring treatment.
  18. Female subject who is pregnant or lactating.
  19. Unwilling or unable to comply with procedures required in this protocol

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): NCT03102606


Contacts
Contact: Ramon Mohanlal, MD, PhD 917-526-1956 rmohanlal@beyondspringpharma.com
Contact: Ilda Boholli, MPH 973-919-4410 iboholli@beyondspringpharma.com

Locations
United States, California
Stanford University School of Medicine - Cancer Institute Not yet recruiting
Stanford, California, United States, 94305-5827
Contact: Dougles W Blayney, MD    650-725-6704    dblayney@stanford.edu   
United States, New York
North Shore Hematology/Oncology Associates, P.C. Recruiting
East Setauket, New York, United States, 11733
Contact: David Chu, MD    646-319-2862    dchu@nshoa.com   
Contact: Jeffrey Vacirca, MD    646-319-2862    jvacirca@nshoa.com   
Sponsors and Collaborators
BeyondSpring Pharmaceuticals Inc.
Chiltern International Inc.
ICON plc
Investigators
Principal Investigator: Douglas W. Blayney, MD Stanford University School of Medicine - Cancer Institute

Responsible Party: BeyondSpring Pharmaceuticals Inc.
ClinicalTrials.gov Identifier: NCT03102606     History of Changes
Other Study ID Numbers: BPI-2358-105
First Posted: April 6, 2017    Key Record Dates
Last Update Posted: April 6, 2017
Last Verified: November 2016
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
Duration of Severe Neutropenia
Bone Pain

Additional relevant MeSH terms:
Neutropenia
Agranulocytosis
Leukopenia
Leukocyte Disorders
Hematologic Diseases
Docetaxel
Diketopiperazines
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Anti-Bacterial Agents
Anti-Infective Agents