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

NCT03102606 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: BPI-2358-105 phase 3
• Study Type: interventional
• Target: 105
• Locations: 4 countries
• Sites: 18

Brief 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 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\*

Conditions

Chemotherapy-induced Neutropenia

Keywords

Plinabulin; Pegfilgrastim; Duration of Severe Neutropenia; Bone Pain

Outcome Measures

Primary Outcomes (1)

• Duration of Severe Neutropenia (DSN)

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

  21 Days

Secondary Outcomes (7)

• Change in Estimated Mean Bone Pain Score

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

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

  Anytime during Cycle 1 (each cycle is 21 days)

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

  15 Days

• Proportion of Patients With Thrombocytopenia

  84 days

• Infections

  84 Days

Study Arms (2)

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

ACTIVE COMPARATOR

Arm 1

Drug: Pegfilgrastim; Other: D5W Placebo

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

EXPERIMENTAL

Arm 2

Drug: Plinabulin; Other: Saline Placebo

Interventions

Plinabulin DRUG

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).

Also known as: BPI-2358, NPI-2358

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

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: Neulasta, G-CSF

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

Saline Placebo OTHER

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

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

D5W Placebo OTHER

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

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

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.
• ECOG performance status of 0 to 1.
• Patients with:
• Phase 2 only:
• Advanced or metastatic NSCLC failing platinum-based therapy
• Phase 3 only:
• 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

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 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.
• 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;

Sponsors & Collaborators

• BeyondSpring Pharmaceuticals Inc.: lead
• Covance: collaborator
• ICON plc: collaborator

Study Sites (18)

Stanford University School of Medicine - Cancer Institute

Stanford, California, 94305-5827, United States

Location

Hematology/Oncology of the North Shore

Skokie, Illinois, 60076, United States

Location

Norton Cancer Institute

Louisville, Kentucky, 40241, United States

Location

Heilongjiang Cancer Hospital

Harbin, Heilongjiang, 150000, China

Location

Jiangsu Cancer Hospital

Nanjing, Jiangsu, 210000, China

Location

Cancer Hospital Chinese Academy of Medical Sciences

Beijing, China

Location

Linyi Cancer Hospital

Linyi, China

Location

Liaoning Cancer Hospital & Institute

Shenyang, China

Location

Henan Cancer Hospital

Zhengzhou, China

Location

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

Pyatigorsk, 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

Dnipropetrovsk City Multifunctional Hospital

Dnipro, 49102, Ukraine

Location

Prykarpatskiy Regional Oncological Center

Ivano-Frankivsk, 76000, Ukraine

Location

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

Kherson, 73000, Ukraine

Location

Kryvyi Rih Oncology Dispensary

Kryvyi Rih, 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

Related Publications (2)

• 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.

  PMID: 35084480 DERIVED

• 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.

  PMID: 32970104 DERIVED

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

Study Officials

• Douglas W. Blayney, MD

  Stanford University School of Medicine - Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Plinabulin and pegfilgrastim are each masked using a double-dummy design in phase 3. Docetaxel administration is not masked.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2017
• First Posted: April 6, 2017
• Study Start: May 29, 2018
• Primary Completion: December 12, 2018
• Study Completion: February 8, 2021
• Last Updated: August 29, 2024
• Results First Posted: August 29, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

RU (3); US (3); CN (6); UA (6)