Plinabulin vs. Pegfilgrastim in Patients With Solid Tumors Receiving Docetaxel Myelosuppressive Chemotherapy Phase 2

NCT04345900 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: BPI-2358-105 Phase 2
• Study Type: interventional
• Target: 55
• Locations: 4 countries
• Sites: 19

Brief 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). 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).

Conditions

Chemotherapy-induced Neutropenia

Outcome Measures

Primary Outcomes (1)

• DSN

  Duration of Grade 4 neutropenia (ANC \< 0.5 × 109/L)

  At the end of Cycle 1 (each cycle is 21 days)

Secondary Outcomes (8)

• Peak Plasma Concentration (Cmax)

  0, 0.5, 1, 4.5, 24 hours post-dose

• Area Under Curve (AUC)

  0, 0.5, 1, 4.5, 24 hours post-dose

• Terminal Half-time (T1/2)

  0, 0.5, 1, 4.5, 24 hours post-dose

• Volume of Distribution in the Terminal Elimination Phase (Vz)

  0, 0.5, 1, 4.5, 24 hours post-dose

• Clearance (Cl)

  0, 0.5, 1, 4.5, 24 hours post-dose

Study Arms (4)

20 mg/m^2 Plinabulin

EXPERIMENTAL

75 mg/m\^2 Docetaxel + 20 mg/m\^2 Plinabulin

Drug: Plinabulin

10 mg/m^2 Plinabulin

EXPERIMENTAL

75 mg/m\^2 Docetaxel + 10 mg/m\^2 Plinabulin

Drug: Plinabulin

5 mg/m^2 Plinabulin

EXPERIMENTAL

75 mg/m\^2 Docetaxel + 5 mg/m\^2 Plinabulin

Drug: Plinabulin

6 mg Pegfilgrastim

ACTIVE COMPARATOR

75 mg/m\^2 Docetaxel + 6 mg Pegfilgrastim

Drug: Pegfilgrastim

Interventions

Plinabulin DRUG

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).

10 mg/m^2 Plinabulin; 20 mg/m^2 Plinabulin; 5 mg/m^2 Plinabulin

Pegfilgrastim DRUG

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.

Also known as: G-CSF

6 mg Pegfilgrastim

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• BeyondSpring Pharmaceuticals Inc.: lead

Study Sites (19)

Emad Ibrahim, MD, Inc.

Redlands, California, 92373, United States

Location

Mid Florida Hematology & Oncology Center

Orange City, Florida, 32763, United States

Location

Cancer Center of Middle Georgia

Dublin, Georgia, 31021, United States

Location

Hematology/Oncology of the North Shore

Skokie, Illinois, 60076, United States

Location

Harbin Medical University Cancer Hospital

Harbin, Harbin, 150000, China

Location

Henan Cancer Hospital

Zhengzhou, Henan, 450008, China

Location

Jiangsu Cancer Hospital

Nanjing, Jiangsu, 210000, China

Location

Medical University 'REAVIZ'

Samara, 443001, Russia

Location

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

Sochi, 354067, Russia

Location

Volgograd Regional Clinical Oncology Dispensary

Volgograd, 400138, Russia

Location

Municipal Institution Dnipropetrovsk City Multi-functional Hospital

Dnipro, 49102, Ukraine

Location

Prykarpatian Clinical Oncological Center

Ivano-Frankivsk, 76000, Ukraine

Location

Kherson regional oncological dispensary Communal Institution of Kherson Regional council

Kherson, 73000, Ukraine

Location

Regional Municipal Institution "Kryvyy Rig Oncology Dispensary"

Krivói Rog, 50048, Ukraine

Location

Kirovograd Regional Oncological Center

Kropyvnytskyi, 25011, Ukraine

Location

Kyiv City Clinical Oncology Center

Kyiv, 03115, Ukraine

Location

Lviv State Oncological Regional Treatment and Preventive Center

Lviv, 79031, Ukraine

Location

Municipal Institution "Sumy Regional Clinical Oncology Dispensary"

Sumy, 40022, Ukraine

Location

Zakarpattia Regional Clinical Oncology Center

Uzhhorod, 88000, Ukraine

Location

MeSH Terms

Interventions

NPI 2358; pegfilgrastim; Granulocyte Colony-Stimulating Factor

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Results Point of Contact

• Title: Ramon Mohanlal
• Organization: BeyondSpring Pharmaceuticals

rmohanlal@beyondspringpharma.com

6468491102

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 31, 2020
• First Posted: April 15, 2020
• Study Start: April 5, 2017
• Primary Completion: March 20, 2018
• Study Completion: April 20, 2018
• Last Updated: May 16, 2024
• Results First Posted: May 16, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (4); RU (3); UA (9); CN (3)