Docetaxel + Plinabulin Compared to Docetaxel + Placebo in Patients With Advanced NSCLC
DUBLIN-3
Randomized Blinded Phase III Assessment of Second or Third-Line Chemotherapy With Docetaxel + Plinabulin Compared to Docetaxel + Placebo in Patients With Advanced Non-Small Cell Lung Cancer and With at Least One Measurable Lung Lesion
1 other identifier
interventional
559
3 countries
57
Brief Summary
To compare the overall survival of NSCLC patients receiving 2nd- or 3rd-line systemic therapy with docetaxel + plinabulin (DP Arm) to patients treated with docetaxel + placebo (D5W) (D Arm) for advanced or metastatic disease. Secondary purposes of the study are:
- To compare overall response rate (ORR) of NSCLC patients receiving 2nd- or 3rd-line systemic therapy with docetaxel + plinabulin (DP Arm) to patients treated with docetaxel + placebo (D5W) (D Arm) for advanced or metastatic disease.
- To compare progression free survival (PFS) of NSCLC patients receiving 2nd- or 3rd-line systemic therapy with docetaxel + plinabulin (DP Arm) to patients treated with docetaxel + placebo (D5W) (D Arm) for advanced or metastatic disease.
- To compare incidence of Grade 4 neutropenia (absolute neutrophil count \[ANC\] \< 0.5 × 109/L) on Day 8 (+/- 1 day) of Cycle 1 of NSCLC patients receiving 2nd- or 3rd-line systemic therapy with docetaxel + plinabulin (DP Arm) to patients treated with docetaxel + placebo (D5W) (D Arm) for advanced or metastatic disease.
- To compare 24-month and 36-month OS rate of NSCLC patients receiving 2nd- or 3rd-line systemic therapy with docetaxel + plinabulin (DP Arm) to patients treated with docetaxel + placebo (D5W) (D Arm) for advanced or metastatic disease.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3 nonsmall-cell-lung-cancer
Started Dec 2015
Typical duration for phase_3 nonsmall-cell-lung-cancer
57 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 16, 2015
CompletedFirst Posted
Study publicly available on registry
July 22, 2015
CompletedStudy Start
First participant enrolled
December 1, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 23, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
May 23, 2021
CompletedSeptember 10, 2022
September 1, 2022
5.3 years
July 16, 2015
September 9, 2022
Conditions
Outcome Measures
Primary Outcomes (1)
Overall Survival
Overall survival of NSCLC patients receiving 2nd- or 3rd-line systemic therapy
Mid-February 2021 (Approximately 2 years after study initiation)
Secondary Outcomes (13)
ORR
Approximately 2 years after study initiation.
PFS
Approximately 2 years after study initiation.
Severe Neutropenia
Day 8 of Cycle 1
Month 24 OS Rate
24-month after study initiation
Month 36 OS Rate
36 month after study initiation
- +8 more secondary outcomes
Study Arms (2)
Docetaxel (D)
ACTIVE COMPARATORA treatment cycle is 21 days. Treatment will be repeated until disease progression is detected by imaging studies or unacceptable toxicities are encountered. On Day 1, all patients will receive docetaxel 75 mg/m2 by intravenous (IV) infusion over 1 hour. Oral dexamethasone (16 mg, given as 8 mg twice daily) will be given on the day prior to, the day of (Day 1), and the day following docetaxel infusion (Day 2). Antiemetic prophylaxis will be administered according to institutional guideline for docetaxel. Institutional guideline/practice should be followed in the event of infusion/hypersensitivity reaction. Diphenhydramine and dexamethasone infusion may be administered in the event of infusion reaction.
Docetaxel + Plinabulin (DP)
EXPERIMENTALThe treatment regimen for Docetaxel (D) will be followed for this arm. In addition, on Days 1 and 8 of the 21 day cycle, patients will receive Plinabulin (P) administered via IV infusion over 60 minutes. On Day 1, the infusion begins 2 hours from the starting time of docetaxel infusion, i.e, approximately 60 minutes from the end of docetaxel infusion. On Day 8, patients must be given an anti-emetic prophylactically before the plinabulin infusion. If emesis persists after Day 8, with a grade \>1, plinabulin will be reduced to 20 mg/m2. Patients from the DP Arm who stop treatment with docetaxel due to toxicity or another medically acceptable reason, may continue treatment with plinabulin alone as previously described.
Interventions
Docetaxel 75 mg/m2 IV + Plinabulin 30 mg/m2
Docetaxel 75 mg/m2 IV
Eligibility Criteria
You may qualify if:
- Males and females ≥ 18 years of age
- ECOG performance status ≤ 2.
- Histopathologically or cytologically confirmed non-squamous or squamous NSCLC.
- Patients with active brain metastasis or leptomeningeal involvement with brain metastases who are asymptomatic, and whose lesions by imaging are at least stable and without interim development of new lesions for at least 4 weeks may be enrolled. Patients who require continued therapy with steroid medication for management for their brain metastases are eligible; dosing must be stable for at least 4 weeks prior to randomization;
- Patients must have at least one measurable lung lesion of ≥10 mm by CT or MRI per RECIST 1.1 criteria. Radiographic tumor assessment is to be performed within 28 days prior to randomization;
- All patients with non-squamous NSCLC must have been tested for 19 deletion and exon 21 L858R substitution mutation. Only patients without EGFR sensitizing mutations are eligible, and they must have progressed on platinum-based chemotherapy. Patients with known ALK-rearrangements should be treated with an appropriate tyrosine kinase inhibitor (TKI) before entering the study. The TKI regimen would count as a line of treatment.
- All adverse events of any prior systemic therapy, surgery, or radiotherapy, must have resolved to CTCAE (v4.03) Grade ≤2, except for neurological adverse events that must have resolved to Grade ≤1;
- The following laboratory results from the central laboratory within 14 days prior to Cycle 1 Day 1 study drug administration.
- Hemoglobin ≥9 g/dL independent of transfusion or growth factor support;
- Absolute neutrophil count ≥1.5 x 109/L independent of growth factor support;
- Platelet count ≥100 x 109/L independent of transfusion or growth factor support;
- Serum total bilirubin ≤ ULN, unless the patient has a diagnosis of Gilbert's disease in which case serum bilirubin ≤3.0 times ULN;
- AST and ALT ≤2.5 x ULN (≤1.5 x ULN if alkaline phosphatase is \>2.5 x ULN);
- Serum creatinine ≤1.5 x ULN;
- Life expectancy more than 12 weeks;
- +5 more criteria
You may not qualify if:
- Administration of chemotherapy, immunotherapy, biological, targeted, or radiation therapy or investigational agent (therapeutic or diagnostic) within 3 weeks prior to receipt of study medication. Major surgery, other than diagnostic surgery, within 4 weeks before first study drug administration.
- Significant cardiac history:
- History of myocardial infarction or ischemic heart disease within 1 year (within a window of 18 days) before first study drug administration;
- Uncontrolled arrhythmia;
- History of congenital QT prolongation;
- ECG findings consistent with active ischemic heart disease;
- New York Heart Association Class III or IV cardiac disease;
- Uncontrolled hypertension: blood pressure consistently greater than 150 mm Hg systolic and 100 mm Hg diastolic in spite of antihypertensive medication.
- Patients who have received prior treatment with docetaxel.
- Prior transient ischemic attack or cerebrovascular accident within the past year (within an 18-day window). Any neurologic toxicities ≥ Grade 2 within 3 weeks of randomization.
- 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.
- Active uncontrolled bacterial, viral, or fungal infection requiring systemic therapy.
- Known infection with human immunodeficiency virus (HIV) or active hepatitis A, B, or C.
- Known prior hypersensitivity reaction to any product containing polysorbate 80, polyoxyethylene 15 hydroxystearate/Macrogol 15 hydroxystearate (Solutol HS 15/ Kolliphor HS 15).
- Female subject who is pregnant or lactating.
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (57)
Ironwood Cancer & Research Centers
Chandler, Arizona, 85224, United States
Pacific Cancer Medical Center, Inc.
Anaheim, California, 92801, United States
Innovative Clinical Research Institute
Whittier, California, 90603, United States
Memorial Health Care System
Colorado Springs, Colorado, 80909, United States
Cancer Center of Central Connecticut
Plainville, Connecticut, 06062, United States
Peachtree Hematoloy-Oncology Consultants, PC
Atlanta, Georgia, 30318, United States
Orchard Healthcare Research Inc.
Skokie, Illinois, 60077, United States
Carle Cancer Center
Urbana, Illinois, 61801, United States
Kansas University Medical Center
Westwood, Kansas, 00913, United States
University of Louisville-Brown Cancer Center
Louisville, Kentucky, 40202, United States
Henry Ford Hospital
Detroit, Michigan, 48202, United States
Michigan Center of Medical Research
Farmington Hills, Michigan, 48334, United States
Hattiesburg Clinic Hematology/Oncology
Hattiesburg, Mississippi, 39401, United States
Central Care Cancer Center
Bolivar, Missouri, 65613, United States
Wake Forest Baptist Health
Winston-Salem, North Carolina, 27157, United States
University of Cincinnati
Cincinnati, Ohio, 45267, United States
Toledo Cancer Center
Toledo, Ohio, 43623, United States
Allegheny Health Network
Pittsburgh, Pennsylvania, 15212, United States
Cookeville Regional Medical Center Cancer Center
Cookeville, Tennessee, 61801, United States
Blacktown Cancer Centre
Blacktown, New South Wales, 2148, Australia
Border Medical Oncology Research Unit
East Albury, New South Wales, 2640, Australia
Gosford Hospital
Gosford, New South Wales, 2250, Australia
Adult Mater Hospital
South Brisbane, Queensland, 4101, Australia
Peninsula and South East Oncology
Melbourne, Victoria, 3199, Australia
Epworth Hospital
Richmond, Victoria, 3121, Australia
Fiona Stanley Hospital
Murdoch, Western Australia, 6150, Australia
Perth Oncology/Mount Hospital
Perth, Western Australia, 6000, Australia
St John of God Hospital, Subiaco
Subiaco, Western Australia, 6008, Australia
Anhui Provincial Hospital
Hefei, Anhui, 230000, China
Cancer Hospital Chinese Academy of Medical Science
Beijing, Beijing Municipality, 100021, China
Beijing Cancer Hospital
Beijing, Beijing Municipality, 100142, China
The PLA General Hospital
Beijing, Beijing Municipality, 100853, China
The First Affiliated Hospital of Xiamen University
Xiamen, Fujian, 361000, China
Zhongshan Hospital Xiamen University
Xiamen, Fujian, 361000, China
Guizhou Provincial Hospital
Guiyang, Guizhou, 550002, China
The Fourth Hospital of Hebei Medical University
Shijiazhuang, Hebei, 050011, China
Affiliated Cancer Hospital of Harbin Medical Unive
Harbin, Heilongjiang, 150040, China
Henan Cancer Hospital
Zhengzhou, Henan, 450008, China
The Second Xiangya Hospital of Central South Unive
Changsha, Hunan, 410011, China
Jiangyin People's Hospital
Jiangyin, Jiangsu, 214400, China
Jiangsu Cancer Hospital
Nanjing, Jiangsu, 210009, China
Nantong Tumor Hospital
Nantong, Jiangsu, 226361, China
Jiangxi Provincial Tumor Hospital
Nanchang, Jiangxi, 330000, China
Jilin Province Cancer Hospital
Changchun, Jilin, 100013, China
Liaoning Cancer Hospital & Institute
Shenyang, Liaoning, 110042, China
The First Affiliated Hospital of Xi'an Jiaotong U
Xi'an, Shaanxi, 710061, China
Shandong Cancer Hospital
Jinan, Shangdong, 250117, China
527-Linyi Cancer Hospital
Linyi, Shangdong, 276000, China
Yantai Yuhuangding Hospital
Yantai, Shangdong, 264000, China
Shanghai Chest Hospital, Shanghai Jiaotong Univers
Shanghai, Shanghai Municipality, 200030, China
The Fifth People's Hospital of Shanghai
Shanghai, Shanghai Municipality, 200240, China
West China Hospital of Sichuan University
Chengdu, Sichuan, 610041, China
Tianjin People's Hospital
Tianjin, Tianjin Municipality, 300060, China
Affiliated Tumor Hospital of Xinjiang Medical Univ
Ürümqi, Xinjiang, 830011, China
Sir Run Run Shaw Hospital, Zhejiang University
Hangzhou, Zhejiang, 310016, China
Zhejiang Cancer Hospital
Hangzhou, Zhejiang, 310022, China
The First Affiliated Hospital, Zhejiang University
Hanzhou, Zhejiang, 310003, China
Related Publications (1)
Han B, Feinstein T, Shi Y, Chen G, Yao Y, Hu C, Shi J, Feng J, Wu H, Cheng Y, Guo QS, Jie Z, Ye F, Zhang Y, Liu Z, Mao W, Zhang L, Lu J, Zhao J, Bazhenova L, Ruiz J, Kloecker GH, Sujith KR, Oliff IA, Wong M, Liu B, Wu Y, Huang L, Sun Y; DUBLIN-3 study group. Plinabulin plus docetaxel versus docetaxel in patients with non-small-cell lung cancer after disease progression on platinum-based regimen (DUBLIN-3): a phase 3, international, multicentre, single-blind, parallel group, randomised controlled trial. Lancet Respir Med. 2024 Oct;12(10):775-786. doi: 10.1016/S2213-2600(24)00178-4. Epub 2024 Sep 9.
PMID: 39265599DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- SINGLE
- Who Masked
- PARTICIPANT
- Masking Details
- placebo
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 16, 2015
First Posted
July 22, 2015
Study Start
December 1, 2015
Primary Completion
March 23, 2021
Study Completion
May 23, 2021
Last Updated
September 10, 2022
Record last verified: 2022-09
Data Sharing
- IPD Sharing
- Will not share