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Chemotherapy-induced NeutropeniaPhase 3NCT03294577

Plinabulin vs. Pegfilgrastim in Prevention of TAC Induced Neutropenia

A Phase 3 study testing Pegfilgrastim, Plinabulin and Docetaxel, doxorubicin, and cyclophosphamide (TAC) in people with Chemotherapy-induced Neutropenia, run by BeyondSpring Pharmaceuticals Inc. at 20 sites in 2 countries.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Chemotherapy-induced Neutropenia
What is being tested?
Pegfilgrastim, Plinabulin and Docetaxel, doxorubicin, and cyclophosphamide (TAC)
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
221 participants
Where
20 sitesin 2 countries
Study dates
23 Oct 2019to 25 Sep 2025
Phase
Phase 3
Are there results?
None posted in the registry

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
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
Show all 25Show fewer
  • 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
  • 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 active malignancy requiring active therapy.
  • Known human immunodeficiency virus (HIV) seropositivity.
  • 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.
  • Female patient who is pregnant or lactating.
  • Use of prophylactic antibiotics.
  • Unwilling or unable to comply with procedures required in this protocol.
  • History of allergy to any of the study drugs.

Trial locations and contacts

20 sites in 2 countries.

20 sites in 2 countries

Ukraine13 sites

  • Dnipropetrovsk City Multifunctional Hospital #4 Oncology Department

    Dnipro, 49102

  • Prykarpatskiy Regional Oncological Center

    Ivano-Frankivsk

  • Regional Clinical Oncology Center

    Kharkiv

  • V.T. Zaycev Institute

    Kharkiv

  • Kirovograd Regional Oncological Center

    Kropyvnytskyi, 25011

  • Public Institution Kryvyi Rih Oncology Center

    Krutyi Bereh, 50048

  • Hemotherapy Department

    Kyiv

  • Kyiv City Clinical Oncological Center

    Kyiv

  • Lviv State Oncological Regional

    Lviv

  • Odessa regional clinical hospital Thoracic Surgery Department Academician Zabolotnoho

    Odesa, 65025

  • Zakarpattia Regional Clinical Oncology Center

    Uzhhorod

  • Vinnytsya Regional Clinical Oncology Dispensary

    Vinnytsia

  • Zaporizhia Regional Clinical Oncology Dispensary

    Zaporizhzhya

Other trials in Ukraine

China7 sites

  • China-Japan Union Hospital of Jilin University Tumor department of Hematology

    Changchun, Jilin, 130000

  • Cancer Center of Guangzhou Medical University

    Guangzhou, Guangdong

  • Cancer Center of Guangzhou Medical University Breast Oncology

    Guangzhou, Guangzhou, 510000

  • No. 1 Banshandong Road

    Hangzhou, Gongshu District

  • Harbin Medical University Cancer Hospital

    Harbin, Harbin, 150000

  • Liaoning Cancer Hospital & Institute

    Shenyang, Shenyang, 110000

  • Fourth Hospital of Hebei Medical University Breast cancer department

    Shijiazhuang, Hebei, 500000

Other trials in China

About this study

Official title: 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)

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.

Read the 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).

The long-term safety follow-up through patients contacts by phone calls, letters or electronic means; or medical records reviews will be conducted to all subjects approximately every 6 months up to 5 years to monitor long term safety of plinabulin.

Being tested
Pegfilgrastim, Plinabulin, D5W Placebo, Docetaxel, doxorubicin, and cyclophosphamide (TAC)
Keywords
Plinabulin, Pegfilgrastim, Chemotherapy induced neutropenia, bone pain

What participants receive

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

  • 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.

  • 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).

  • D5W PlaceboOther

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

  • Docetaxel, doxorubicin, and cyclophosphamide (TAC)Drug

    Also called Taxotere, Adriamycin, Cytoxan

    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.

Study groups in NCT03294577
Study groupRoleWhat they receive
TAC + PegfilgrastimActive comparatorPhase 3:TAC + Pegfilgrastim (6 mg)+ D5W placebo D5W Placebo: 250 ml D5W to match the administration of plinabulin diluted in 250 ml D5W
Receives: Drug: Pegfilgrastim; Other: D5W Placebo; Drug: Docetaxel, doxorubicin, and cyclophosphamide (TAC)
TAC + Pegfilgrastim + PlinabulinExperimentalPhase 3: TAC+ Plinabulin (40 mg) + Pegfilgrastim (6 mg)
Receives: Drug: Plinabulin; Drug: Docetaxel, doxorubicin, and cyclophosphamide (TAC)

What is being measured

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

  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)

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

Secondary outcomes (7)

  1. Mean DSN assessment

    DSN is defined as Days of Grade 4 Neutropenia (ANC less than 0.5 X 109/L)

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

  2. Mean ANC nadir

    record and evaluate the lowest ANC value

    Measured: Duration of first cycle (21 days)

  3. Percentage of Patients without grade 3 and grade 4 neutropenia

    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.

    Measured: Duration of first cycle (21 days)

  4. Mean DSN assessment within 15 days

    To evaluate the effect of Plinabulin related to DSN within 15 days

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

  5. Average change in bone pain

    Record the bone pain score from the numerical rating scale (NRS)

    Measured: From -1 day over the observational period

  6. Rate of composite risks

    Composite risks includes infection, FN, hospitalization, significant disability, life threatening and death

    Measured: Duration of all 4 cycle (21 days)

  7. Percentage of patients with relative dose intensity < 85%

    Assess the percentage of patients with RDI < 85%

    Measured: Duration of all 4 cycle (21 days)

Timeline

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

  1. First posted27 Sep 2017
  2. Study start23 Oct 2019
  3. Primary completion25 Sep 2020
  4. Study completion25 Sep 2025 (estimated)

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
Supportive care
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
221 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03294577
Sponsor's protocol ID
BPI-2358-106 phase 3
Status last verified
Jan 2021
First submitted
22 Sep 2017
Last updated
15 Jan 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Pegfilgrastim, Plinabulin and Docetaxel, doxorubicin, and cyclophosphamide (TAC) in people with Chemotherapy-induced Neutropenia, run by BeyondSpring Pharmaceuticals Inc. at 20 sites in 2 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 11 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: status not confirmed, as of the sponsor's last update on 15 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 20 sites in Ukraine, China. 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?

Results are not available in the source record.

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?

Percentage of patients with Duration of Severe Neutropenia (DSN) =0 (time frame: Duration of Grade 4 neutropenia assessed during the first cycle (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 NCT03294577.

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 15 Jan 2021.

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