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Chemotherapy-induced NeutropeniaPhase 2NCT04227990

Plinabulin iv Solution in Prevention of TAC Induced Neutropenia

A Phase 2 study testing Plinabulin, Pegfilgrastim and Docetaxel, doxorubicin, and cyclophosphamide (TAC) in people with Chemotherapy-induced Neutropenia, run by BeyondSpring Pharmaceuticals Inc. at 11 sites in 2 countries.

Completed

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

Official record
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Trial 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… 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?
Plinabulin, Pegfilgrastim and Docetaxel, doxorubicin, and cyclophosphamide (TAC)
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
115 participants
Where
11 sitesin 2 countries
Study dates
27 Nov 2017to 3 Jan 2019
Phase
Phase 2
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, and 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 Are within 60 days of a diagnostic or surgical procedure (biopsy, umpectomy, mastectomy), and Have had no prior chemotherapy.
  • Pathological confirmation of cancer is required.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
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  • Have life expectancy of 3 months or more.
  • The following laboratory results provided by the central laboratory within 14 days prior to study drug administration:
  • ANC ≥ 1.5 x 10^9/L independent of growth factor support; hemoglobin ≥ 9 g/dL independent of transfusion or growth factor support; calculated creatinine clearance (CLcr) ≥ 60 mL/min using Cockcroft-Gault formula; Serum total bilirubin ≤ upper limit of normal (ULN); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) as 2.5 x ULN (≤ 1.5 x ULN if alkaline phosphate is > 2.5 x ULN).
  • 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. Women 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 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.

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.
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  • 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 prior doxorubicin (>240 mg/m2) or anthracycline exposure that would preclude the safe administration of TAC chemotherapy as described in the protocol.
  • 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

11 sites in 2 countries.

11 sites in 2 countries

Ukraine6 sites

  • Dnipropetrovsk City Multifunctional Hospital #4 Oncology Department

    Dnipro, 49102

  • Prykarpatskiy Regional Oncological Center

    Ivano-Frankivsk, 76000

  • "V.T. Zaycev Institute of General and Urgent Surgery NAMS of Ukraine Dept. of Oncology

    Kharkiv, 61103

  • Kirovograd Regional Oncological Center

    Kropyvnytskyi, 25011

  • Public Institution Kryvyi Rih Oncology Center

    Krutyi Bereh, 50048

  • Odessa regional clinical hospital Thoracic Surgery Department Academician Zabolotnoho

    Odesa, 65025

Other trials in Ukraine

China5 sites

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

    Changchun, Jilin, 130000

  • Cancer Center of Guangzhou Medical University Breast Oncology

    Guangzhou, Guangzhou, 510000

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

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.

Read the detailed description

This is a multi-center randomized study, Phase 2 study. 115 patients were enrolled in Phase 2. Two regimens were evaluated in Phase 2: a plinabulin monotherapy regimen and a combination therapy regimen of plinabulin + pegfilgrastim. The monotherapy regimen includes 4 arms: pegfilgrastim 6.0 mg alone; and 10, 20, or 30 mg/m2 plinabulin.

The combination regimen includes 4 arms: pegfilgrastim 6.0 mg alone; and 20 mg/m2 plinabulin + pegfilgrastim 1.5, 3, or 6.0 mg. The pegfilgrastim 6.0 mg alone arm is the control arm for comparison with the monotherapy and combination therapy arms for the interim evaluation.

The purpose of this study is to compare the duration of severe neutropenia (DSN) in patients with early stage (Stage I and II) and Stage III breast cancer (node positive or node negative with high risk of recurrence) receiving docetaxel, doxorubicin, and cyclophosphamide (TAC) and monotherapy plinabulin or combination therapy plinabulin/pegfilgrastim. Severe neutropenia is an absolute neutrophil count (ANC) <0.5 × 10^9/L.

Docetaxel, doxorubicin, and cyclophosphamide (TAC) were 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 was 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.

64 patients were enrolled for monotherapy evaluation and 51 patients were enrolled for the combination therapy Arm 5, 6 and 7 for efficacy and safety evaluation. The arm designation and planned intervention is as follows:

For monotherapy:

Arm 1: TAC + pegfilgrastim (6.0 mg)

Arm 2: TAC + plinabulin (10 mg/m2).

Arm 3: TAC + plinabulin (20 mg/m2).

Arm 4: TAC + plinabulin (30 mg/m2).

For combination therapy:

Arm 1: TAC + pegfilgrastim (6.0 mg)

Arm 5: TAC + plinabulin (20 mg/m2) + pegfilgrastim (1.5 mg)

Arm 6: TAC + plinabulin (20 mg/m2) + pegfilgrastim (3.0 mg)

Arm 7: TAC + plinabulin (20 mg/m2) + pegfilgrastim (6.0 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 in Arms 2, 3 and 4 will receive a single dose of plinabulin, 30 minutes after the end of the TAC (or TC for Cycles 2 to 4) infusion on Day 1. The plinabulin dose will be infused over 30 minutes (±5 minutes) in Arms 2 and 3 and over 60 minutes (±5 minutes) in Arm 4 (in order to improve tolerability at the higher 30 mg/m2 dose level).

On Day 2 of each cycle (≥24 hours after completing chemotherapy) patients in Arm 1 and in combination therapy will receive a single dose of pegfilgrastim (1.5, 3.0, or 6.0 mg) (subcutaneous injection).

Being tested
Plinabulin, Pegfilgrastim, Docetaxel, doxorubicin, and cyclophosphamide (TAC)

What participants receive

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

  • PlinabulinDrug

    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

    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.

  • Docetaxel, doxorubicin, and cyclophosphamide (TAC)Drug

    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 NCT04227990
Study groupRoleWhat they receive
TAC + Pegfilgrastim (6 mg)Active comparatorNot described
Receives: Drug: Pegfilgrastim; Drug: Docetaxel, doxorubicin, and cyclophosphamide (TAC)
TAC + Plinabulin 10 mg/m^2ExperimentalNot described
Receives: Drug: Plinabulin; Drug: Docetaxel, doxorubicin, and cyclophosphamide (TAC)
TAC + Plinabulin 20 mg/m^2ExperimentalNot described
Receives: Drug: Plinabulin; Drug: Docetaxel, doxorubicin, and cyclophosphamide (TAC)
TAC + Plinabulin 30 mg/m^2ExperimentalNot described
Receives: Drug: Plinabulin; Drug: Docetaxel, doxorubicin, and cyclophosphamide (TAC)
TAC + Pegfilgrastim (1.5 mg) + Plinabulin (20 mg/m^2)ExperimentalNot described
Receives: Drug: Plinabulin; Drug: Pegfilgrastim; Drug: Docetaxel, doxorubicin, and cyclophosphamide (TAC)
TAC + Pegfilgrastim (3 mg) + Plinabulin (20 mg/m^2)ExperimentalNot described
Receives: Drug: Plinabulin; Drug: Pegfilgrastim; Drug: Docetaxel, doxorubicin, and cyclophosphamide (TAC)
TAC + Pegfilgrastim (6 mg) + Plinabulin (20 mg/m^2)ExperimentalNot described
Receives: Drug: Plinabulin; Drug: Pegfilgrastim; Drug: Docetaxel, doxorubicin, and cyclophosphamide (TAC)

What is being measured

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

  1. Duration of Severe Neutropenia (DSN)

    Days with Severe Neutropenia in treatment Cycle 1

    Measured: Cycle 1 (21 days)

Secondary outcomes (4)

  1. Frequency of Grade 4 neutropenia

    Frequency of patients with at least 1 day of Grade 4 neutropenia (ANC <0.5 × 109/L)

    Measured: Cycle 1 (21 days)

  2. Bone pain score

    Mean pain score from the patient bone pain scale from pre-dose Day 1 to Day 8 in Cycle 1 (0-10 scale, higher score means worse outcome)

    Measured: Cycle 1 (21 days)

  3. Change in bone pain score

    Change in bone pain score from pre-dose Day 1 through Day 8 in Cycle1 (0-10 scale, higher score means worse outcome)

    Measured: Cycle 1 (21 days)

  4. Adverse events

    Incidences, occurrences, and severity of AEs/SAEs Cycle 1-4

    Measured: Cycle 1 - 4 (21-day cycle)

Timeline

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

  1. First posted14 Jan 2020
  2. Study start27 Nov 2017
  3. Primary completion15 Oct 2018
  4. Study completion3 Jan 2019

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 2
Primary purpose
Supportive care
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
115 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04227990
Sponsor's protocol ID
BPI-2358-106 Phase 2
Status last verified
Jan 2020
First submitted
10 Jan 2020
Last updated
18 Jan 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Plinabulin, Pegfilgrastim and Docetaxel, doxorubicin, and cyclophosphamide (TAC) in people with Chemotherapy-induced Neutropenia, run by BeyondSpring Pharmaceuticals Inc. at 11 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 13 inclusion and 21 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 18 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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: Cycle 1 (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 NCT04227990.

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 18 Jan 2020.

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