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Chemotherapy-induced NeutropeniaPhase 3Protective-1NCT03102606

Plinabulin vs. Pegfilgrastim in Patients With Solid Tumors Receiving Docetaxel Myelosuppressive Chemotherapy Phase 3

A Phase 3 study testing Plinabulin and Pegfilgrastim in people with Chemotherapy-induced Neutropenia, run by BeyondSpring Pharmaceuticals Inc. at 18 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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; locally advanced or metastatic non small cell lung cancer (NSCLC) after platinum therapy failure; or hormone refractory (androgen… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Chemotherapy-induced Neutropenia
What is being tested?
Plinabulin and Pegfilgrastim
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
105 participants
Where
18 sitesin 4 countries
Study dates
29 May 2018to 8 Feb 2021
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • At least ≥ 18 years of age (male or female) at the time of signing the informed consent form.
  • ECOG performance status of 0 to 1.
  • Patients with:
  • Phase 2 only:
  • Advanced or metastatic NSCLC failing platinum-based therapy
  • Phase 3 only:
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  • Advanced or metastatic breast cancer, who have failed < 5 prior lines of chemotherapy (Note that study treatment may be the first chemotherapy treatment for advanced or metastatic cancer)
  • locally advanced or metastatic NSCLC after platinum therapy failure
  • HRPC (Note that study treatment may be the first chemotherapy treatment)
  • Pathology confirmation of cancer is required.
  • 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):
  • 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
  • Life expectancy of 3 months or more.
  • The following laboratory results assessed within 14 days prior to study drug administration:
  • Hemoglobin >/= 9 g/dL independent of transfusion or growth factor support
  • Absolute neutrophil count (ANC) >/= 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 </= 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
  • Note: Results are from the central laboratory. Local laboratory results 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)/International Normalized Ratio (INR) ≤ 1.5 × upper limit of normal (ULN), activated partial thromboplastin time (PTT) ≤ 1.5 × ULN, based on central laboratory results.
  • 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.

Who cannot join

  • History of myelogenous leukemia, myelodysplastic syndrome or concomitant sickle cell disease.
  • Received chemotherapy within 4 weeks prior to the first dose of study drug.
  • Received prior docetaxel treatment, except adjuvant docetaxel given > 1 year prior to first dose of study drug
  • Phase 3 only: Received >/= 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).
  • 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
  • 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 CTCAE (v4.03) treatment emergent AEs.
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  • Receiving any concurrent anticancer therapies (except continued hormonal treatment).
  • Received a prior bone marrow or stem cell transplant.
  • Has a co-existing active infection or received systemic anti-infective treatment within 72 hours before the first dose of study drug.
  • Prior radiation therapy within the 4 weeks before the first dose of study drug.
  • Prior use of pegfilgrastim or filgrastim within 4 weeks before the first dose of study drug.
  • 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.
  • Significant cardiovascular history:
  • 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 malignancy requiring active therapy.
  • Known human immunodeficiency virus (HIV) seropositivity.
  • Active Hepatitis B virus (HBV) infection which requires antiviral treatment. Patients with detectable Hepatitis B surface Antigen (HBsAg) may be eligible provided the patient has a negative viral load. Patients with a positive HBsAg must have a negative viral load before each chemotherapy administration. 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.
  • Female subject who is pregnant or lactating.
  • Unwilling or unable to comply with procedures required in this protocol

Trial locations and contacts

18 sites in 4 countries.

18 sites in 4 countries

China6 sites

  • Cancer Hospital Chinese Academy of Medical Sciences

    Beijing

  • Heilongjiang Cancer Hospital

    Harbin, Heilongjiang, 150000

  • Linyi Cancer Hospital

    Linyi

  • Jiangsu Cancer Hospital

    Nanjing, Jiangsu, 210000

  • Liaoning Cancer Hospital & Institute

    Shenyang

  • Henan Cancer Hospital

    Zhengzhou

Other trials in China

Ukraine6 sites

  • Dnipropetrovsk City Multifunctional Hospital

    Dnipro, 49102

  • Prykarpatskiy Regional Oncological Center

    Ivano-Frankivsk, 76000

  • Communal Institution of Kherson Regional Council "Kherson regional oncological dispensary"

    Kherson, 73000

  • Kryvyi Rih Oncology Dispensary

    Kryvyi Rih

  • Lviv State Oncological Regional Treatment and Preventive Center

    Lviv, 79031

  • Municipal Institution "Sumy Regional Clinical Oncology Dispensary"

    Sumy, 40022

Other trials in Ukraine

United States3 sites

  • Norton Cancer Institute

    Louisville, Kentucky, 40241

  • Hematology/Oncology of the North Shore

    Skokie, Illinois, 60076

  • Stanford University School of Medicine - Cancer Institute

    Stanford, California, 94305-5827

Other trials in United States

Russia3 sites

  • State Budgetary Healthcare Institution of Stavropol Territory "Pyatigorsk Interregional Oncology Dispensary"

    Pyatigorsk

  • SBI of Healthcare "Oncology Dispensary #2" Ministry of Healthcare of Krasnodar Region

    Sochi, 354067

  • Volgograd Regional Clinical Oncology Dispensary

    Volgograd, 400138

Other trials in Russia

About this study

Official title: A Phase 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)

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; locally advanced or metastatic non small cell lung cancer (NSCLC) after platinum therapy failure; or hormone refractory (androgen independent) metastatic prostate cancer treated with docetaxel (75 mg/m2) + plinabulin (40 mg) versus docetaxel (75 mg/m2) + pegfilgrastim (6 mg). Neutrophils count will be assessed at baseline; Pre dose during Cycle 1, Day 1, 2, 6, 7, 8, 9, 10, 15.

*Study is officially closed on 08 Feb 2021*

Read the detailed description

Arm 1: Docetaxel (75 mg/m2) + pegfilgrastim (6 mg) + placebo matching plinabulin

Arm 2: Docetaxel (75 mg/m2) + plinabulin (40 mg) + placebo matching pegfilgrastim

Being tested
Plinabulin, Pegfilgrastim, Saline Placebo, D5W Placebo
Keywords
Plinabulin, Pegfilgrastim, Duration of Severe Neutropenia, Bone Pain

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PlinabulinDrug

    Also called BPI-2358, NPI-2358

    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).

  • PegfilgrastimDrug

    Also called Neulasta, G-CSF

    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.

  • Saline PlaceboOther

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

  • D5W PlaceboOther

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

Study groups in NCT03102606
Study groupRoleWhat they receive
Docetaxel (75 mg/m2) + pegfilgrastim (6 mg) + placebo matching plinabulinActive comparatorArm 1
Receives: Drug: Pegfilgrastim; Other: D5W Placebo
Docetaxel (75 mg/m2) + plinabulin (40 mg) + placebo matching pegfilgrastimExperimentalArm 2
Receives: Drug: Plinabulin; Other: Saline Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Duration of Severe Neutropenia (DSN)

    Duration of severe neutropenia (ANC < 0.5 × 109/L)

    Measured: 21 Days

Secondary outcomes (7)

  1. Change in Estimated Mean Bone Pain Score

    Change in estimated mean bone pain score from pre-dose Day 1 through Day 8. The bone pain scale assessment was based on the validated Wong-Baker Faces® Pain Rating Scale. The pain scale range is from 0 to 10. The severity of pain marked on a scale is from 0 ('no hurt') to 10 ('hurt worst').

    Measured: Day 1 through 8 in Cycle 1 (each cycle is 21 days)

  2. Change in Patients With at Least 30% Platelet Count From Baseline in Cycle 1

    Patients with platelet count at least 30% change from baseline at any time during Cycle 1

    Measured: Anytime during Cycle 1 (each cycle is 21 days)

  3. Proportion of Patients With Neutrophil-to-lymphocyte Ratio (NLR) > 5

    Proportion of patients with neutrophil-to-lymphocyte ratio (NLR) > 5 from Day 1 through Day 15

    Measured: 15 Days

  4. Proportion of Patients With Thrombocytopenia

    Proportion of patients with thrombocytopenia (all grade) during 4 cycles

    Measured: 84 days

  5. Infections

    Incidence of infections in cycles 1 to 4

    Measured: 84 Days

  6. Antibiotic Use

    Incidence of antibiotic use

    Measured: 21 Days

  7. Sepsis

    To assess the incidence of sepsis

    Measured: 84 Days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Apr 2017
  2. Study start29 May 2018
  3. Primary completion12 Dec 2018
  4. Study completion8 Feb 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
105 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03102606
Sponsor's protocol ID
BPI-2358-105 phase 3
Acronym
Protective-1
Status last verified
Aug 2024
First submitted
6 Mar 2017
Last updated
29 Aug 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Blayney DW, Mohanlal R, Adamchuk H, Kirtbaya DV, Chen M, Du L, Ogenstad S, Ginn G, Huang L, Zhang Q. Efficacy of Plinabulin vs Pegfilgrastim for Prevention of Docetaxel-Induced Neutropenia in Patients With Solid Tumors: A Randomized Clinical Trial. JAMA Netw Open. 2022 Jan 4;5(1):e2145446. doi: 10.1001/jamanetworkopen.2021.45446.

    PubMed 35084480

  • Blayney DW, Zhang Q, Feng J, Zhao Y, Bondarenko I, Vynnychenko I, Kovalenko N, Nair S, Ibrahim E, Udovista DP, Mohanlal R, Ogenstad S, Ette E, Du L, Huang L, Shi YK. Efficacy of Plinabulin vs Pegfilgrastim for Prevention of Chemotherapy-Induced Neutropenia in Adults With Non-Small Cell Lung Cancer: A Phase 2 Randomized Clinical Trial. JAMA Oncol. 2020 Nov 1;6(11):e204429. doi: 10.1001/jamaoncol.2020.4429. Epub 2020 Nov 12.

    PubMed 32970104

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Plinabulin and Pegfilgrastim in people with Chemotherapy-induced Neutropenia, run by BeyondSpring Pharmaceuticals Inc. at 18 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 28 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 18 sites in China, Ukraine, United States, Russia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 Aug 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Duration of Severe Neutropenia (DSN) (time frame: 21 Days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03102606, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Aug 2024; AzTrials last refreshed its copy on 26 Oct 2026.

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