Chemotherapy-induced NeutropeniaPhase 2NCT04345900
Plinabulin vs. Pegfilgrastim in Patients With Solid Tumors Receiving Docetaxel Myelosuppressive Chemotherapy Phase 2
A Phase 2 study testing Plinabulin and Pegfilgrastim in people with Chemotherapy-induced Neutropenia, run by BeyondSpring Pharmaceuticals Inc. at 19 sites in 4 countries.
Trial summary
To assess the duration of severe neutropenia (DSN) in treatment Cycle 1 in patients treated with docetaxel (75 mg/m2) + plinabulin (5, 10, or 20 mg/m2) or with docetaxel (75 mg/m2) + pegfilgrastim (6 mg). 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?
- No, everyone receives an active treatment
- How many people
- 55 participants
- Where
- 19 sitesin 4 countries
- Study dates
- 5 Apr 2017to 20 Apr 2018
- Phase
- Phase 2
- 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.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
- Patients with:
- Advanced or metastatic NSCLC failing platinum based therapy
- Pathology confirmation of cancer
- 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:
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- 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 ANC ≥ 1.5 x 109/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 [AP] is > 2.5 x ULN) Serum creatinine ≤ 1.5 x ULN
- Prothrombin time (PT) and International Normalized Ratio (INR) ≤ 1.5 × upper limit of normal (ULN), activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN, based on central laboratory results.
- Female patients of childbearing potential who had 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 were 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 were sexually active and who were 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, except adjuvant docetaxel given > 1 year prior to first dose of study drug.
- 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 required use of strong CYP3A4 inhibitors (refer to Section 10.6.2)
- 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 AEs (TEAEs).
- Received any concurrent anticancer therapies.
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- Received a prior bone marrow or stem cell transplant.
- Had 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 despite 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.
- Hepatitis B virsu (HBV) or hepatitis C virus (HCV) infection requiring treatment
- Female subject who is pregnant or lactating.
- Unwilling or unable to comply with procedures required in this protocol
Trial locations and contacts
19 sites in 4 countries.
19 sites in 4 countries
Ukraine9 sites
Municipal Institution Dnipropetrovsk City Multi-functional Hospital
Dnipro, 49102
Prykarpatian Clinical Oncological Center
Ivano-Frankivsk, 76000
Kherson regional oncological dispensary Communal Institution of Kherson Regional council
Kherson, 73000
Regional Municipal Institution "Kryvyy Rig Oncology Dispensary"
Krivói Rog, 50048
Kirovograd Regional Oncological Center
Kropyvnytskyi, 25011
Kyiv City Clinical Oncology Center
Kyiv, 03115
Lviv State Oncological Regional Treatment and Preventive Center
Lviv, 79031
Municipal Institution "Sumy Regional Clinical Oncology Dispensary"
Sumy, 40022
Zakarpattia Regional Clinical Oncology Center
Uzhhorod, 88000
United States4 sites
Cancer Center of Middle Georgia
Dublin, Georgia, 31021
Mid Florida Hematology & Oncology Center
Orange City, Florida, 32763
Emad Ibrahim, MD, Inc.
Redlands, California, 92373
Hematology/Oncology of the North Shore
Skokie, Illinois, 60076
China3 sites
Harbin Medical University Cancer Hospital
Harbin, Harbin, 150000
Jiangsu Cancer Hospital
Nanjing, Jiangsu, 210000
Henan Cancer Hospital
Zhengzhou, Henan, 450008
Russia3 sites
Medical University 'REAVIZ'
Samara, 443001
SBI of Healthcare "Oncology Dispensary #2" Ministry of Healthcare of Krasnodar Region
Sochi, 354067
Volgograd Regional Clinical Oncology Dispensary
Volgograd, 400138
About this study
Official title: A Phase 2, Multicenter, Randomized Study to Evaluate Duration of Severe Neutropenia With Plinabulin Versus Pegfilgrastim in Patients With Solid Tumors Receiving Docetaxel Myelosuppressive Chemotherapy (Protective-1)
To assess the duration of severe neutropenia (DSN) in treatment Cycle 1 in patients treated with docetaxel (75 mg/m2) + plinabulin (5, 10, or 20 mg/m2) or with docetaxel (75 mg/m2) + pegfilgrastim (6 mg). Neutrophils count was to be assessed at baseline (prior to Cycle 1 docetaxel dose) and during Cycle 1 on Days 1, 2, 6, 7, 8, 9, 10, and 15 (pre-dose on dosing days; times equivalent to pre dose on other days).
Read the detailed description
55 patients with advanced and metastatic NSCLC have been randomized with the arm designation and planned intervention as follows: Arm 1: Docetaxel (75 mg/m2) + pegfilgrastim (6 mg) Arm 2: Docetaxel (75 mg/m2) + plinabulin (20 mg/m^2) Arm 3: Docetaxel (75 mg/m2) + plinabulin (10 mg/m^2) Arm 4: Docetaxel (75 mg/m2) + plinabulin (5 mg/m^2)
- Conditions
- Chemotherapy-induced Neutropenia
- Being tested
- Plinabulin, Pegfilgrastim
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlinabulinDrug
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 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.
| Study group | Role | What they receive |
|---|---|---|
| 20 mg/m^2 Plinabulin | Experimental | 75 mg/m^2 Docetaxel + 20 mg/m^2 Plinabulin Receives: Drug: Plinabulin |
| 10 mg/m^2 Plinabulin | Experimental | 75 mg/m^2 Docetaxel + 10 mg/m^2 Plinabulin Receives: Drug: Plinabulin |
| 5 mg/m^2 Plinabulin | Experimental | 75 mg/m^2 Docetaxel + 5 mg/m^2 Plinabulin Receives: Drug: Plinabulin |
| 6 mg Pegfilgrastim | Active comparator | 75 mg/m^2 Docetaxel + 6 mg Pegfilgrastim Receives: Drug: Pegfilgrastim |
What is being measured
The primary outcome is the main question the study is designed to answer.
DSN
Duration of Grade 4 neutropenia (ANC < 0.5 × 109/L)
Measured: At the end of Cycle 1 (each cycle is 21 days)
Secondary outcomes (8)
Peak Plasma Concentration (Cmax)
a parameter to establish the pharmacokinetic profile of plinabulin by evaluating the peak plasma concentration (Cmax) of the drug in the blood after administration of a single dose of the drug
Measured: 0, 0.5, 1, 4.5, 24 hours post-dose
Area Under Curve (AUC)
A parameter to establish the pharmacokinetic profile of plinabulin to describe the variation of the drug concentration in blood plasma as a function of time
Measured: 0, 0.5, 1, 4.5, 24 hours post-dose
Terminal Half-time (T1/2)
A parameter to establish the pharmacokinetic profile of plinabulin by measuring the time it takes for the concentration of the drug in the plasma to be reduced by 50%
Measured: 0, 0.5, 1, 4.5, 24 hours post-dose
Volume of Distribution in the Terminal Elimination Phase (Vz)
A parameter to establish the pharmacokinetic profile of plinabulin by evaluating Vz.
Measured: 0, 0.5, 1, 4.5, 24 hours post-dose
Clearance (Cl)
a parameter to establish the pharmacokinetic profile of plinabulin
Measured: 0, 0.5, 1, 4.5, 24 hours post-dose
Systolic Blood Pressure
a parameter to establish the pharmacodynamic profile of plinabulin
Measured: 0, 0.5, 1, 4.5, 24 hours post-dose
Diastolic Blood Pressure
a parameter to establish the pharmacodynamic profile of plinabulin
Measured: 0, 0.5, 1, 4.5, 24 hours post-dose
Area Over the Neutropenia Curve
a parameter to establish the pharmacodynamic profile of plinabulin
Measured: 0, 0.5, 1, 4.5, 24 hours post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Apr 2020
- Study start5 Apr 2017
- Primary completion20 Mar 2018
- Study completion20 Apr 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Chemotherapy-induced NeutropeniaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 55 participants (actual)
Sponsor and investigators
- Lead sponsor
- BeyondSpring Pharmaceuticals Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04345900
- Sponsor's protocol ID
- BPI-2358-105 Phase 2
- Status last verified
- Mar 2024
- First submitted
- 31 Mar 2020
- Last updated
- 16 May 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Multicenter, Randomized Study to Evaluate Duration of Severe Neutropenia With Plinabulin Versus Pegfilgrastim in Patients With Solid Tumors Receiving Docetaxel Myelosuppressive Chemotherapy (Protective-1)
- ClinicalTrials.gov ID
- NCT04345900
- Acronym / sponsor ID
- BPI-2358-105 Phase 2
- Conditions
- Chemotherapy-induced Neutropenia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 55 participants (actual)
- Lead sponsor
- BeyondSpring Pharmaceuticals Inc.Industry (pharma, biotech, devices)
- Study start
- 5 Apr 2017 (actual)
- Primary completion
- 20 Mar 2018 (actual)
- Study completion
- 20 Apr 2018 (actual)
- First posted
- 15 Apr 2020 (actual)
- Results
- Posted 16 May 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To assess the duration of severe neutropenia (DSN) in treatment Cycle 1 in patients treated with docetaxel (75 mg/m2) + plinabulin (5, 10, or 20 mg/m2) or with docetaxel (75 mg/m2) + pegfilgrastim (6 mg). Neutrophils count was to be assessed at baseline (prior to Cycle 1 docetaxel dose) and during Cycle 1 on Days 1, 2, 6, 7, 8, 9, 10, and 15 (pre-dose on dosing days; times equivalent to pre dose on other days).
Detailed description
55 patients with advanced and metastatic NSCLC have been randomized with the arm designation and planned intervention as follows: Arm 1: Docetaxel (75 mg/m2) + pegfilgrastim (6 mg) Arm 2: Docetaxel (75 mg/m2) + plinabulin (20 mg/m^2) Arm 3: Docetaxel (75 mg/m2) + plinabulin (10 mg/m^2) Arm 4: Docetaxel (75 mg/m2) + plinabulin (5 mg/m^2)
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 20 mg/m^2 Plinabulin | Experimental | Drug: Plinabulin75 mg/m^2 Docetaxel + 20 mg/m^2 Plinabulin |
| 10 mg/m^2 Plinabulin | Experimental | Drug: Plinabulin75 mg/m^2 Docetaxel + 10 mg/m^2 Plinabulin |
| 5 mg/m^2 Plinabulin | Experimental | Drug: Plinabulin75 mg/m^2 Docetaxel + 5 mg/m^2 Plinabulin |
| 6 mg Pegfilgrastim | Active comparator | Drug: Pegfilgrastim75 mg/m^2 Docetaxel + 6 mg Pegfilgrastim |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- At least ≥ 18 years of age (male or female) at the time of signing the informed consent form.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
- Patients with:
- Advanced or metastatic NSCLC failing platinum based therapy
- Pathology confirmation of cancer
Key exclusion criteria (19 listed)
- 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, except adjuvant docetaxel given > 1 year prior to first dose of study drug.
- 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 required use of strong CYP3A4 inhibitors (refer to Section 10.6.2)
- 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 AEs (TEAEs).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Plinabulina 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). | Drug | 10 mg/m^2 Plinabulin, 20 mg/m^2 Plinabulin, 5 mg/m^2 Plinabulin |
| PegfilgrastimAlso: G-CSFPEGFILGRASTIM 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. | Drug | 6 mg Pegfilgrastim |
Primary outcome
DSN
Time frame: At the end of Cycle 1 (each cycle is 21 days)
Duration of Grade 4 neutropenia (ANC < 0.5 × 109/L)
8 secondary outcomes
Peak Plasma Concentration (Cmax)
Time frame: 0, 0.5, 1, 4.5, 24 hours post-dose
Area Under Curve (AUC)
Time frame: 0, 0.5, 1, 4.5, 24 hours post-dose
Terminal Half-time (T1/2)
Time frame: 0, 0.5, 1, 4.5, 24 hours post-dose
Volume of Distribution in the Terminal Elimination Phase (Vz)
Time frame: 0, 0.5, 1, 4.5, 24 hours post-dose
Clearance (Cl)
Time frame: 0, 0.5, 1, 4.5, 24 hours post-dose
Systolic Blood Pressure
Time frame: 0, 0.5, 1, 4.5, 24 hours post-dose
Diastolic Blood Pressure
Time frame: 0, 0.5, 1, 4.5, 24 hours post-dose
Area Over the Neutropenia Curve
Time frame: 0, 0.5, 1, 4.5, 24 hours post-dose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 May 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
19 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Plinabulin and Pegfilgrastim in people with Chemotherapy-induced Neutropenia, run by BeyondSpring Pharmaceuticals Inc. at 19 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 19 inclusion and 19 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 16 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 19 sites in Ukraine, United States, China, 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 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?
Yes. Results are posted in the registry (first posted 16 May 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?
DSN (time frame: At the end of Cycle 1 (each cycle is 21 days)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 16 May 2024.