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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02504489




Registration number
NCT02504489
Ethics application status
Date submitted
16/07/2015
Date registered
22/07/2015

Titles & IDs
Public title
Docetaxel + Plinabulin Compared to Docetaxel + Placebo in Patients With Advanced NSCLC
Scientific title
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
Secondary ID [1] 0 0
BPI-2358-103
Universal Trial Number (UTN)
Trial acronym
DUBLIN-3
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-Small Cell Lung Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Docetaxel + Plinabulin (DP)
Treatment: Drugs - Docetaxel (D)

Active comparator: Docetaxel (D) - A 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.

Experimental: Docetaxel + Plinabulin (DP) - The 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.


Treatment: Drugs: Docetaxel + Plinabulin (DP)
Docetaxel 75 mg/m2 IV + Plinabulin 30 mg/m2

Treatment: Drugs: Docetaxel (D)
Docetaxel 75 mg/m2 IV
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Survival
Timepoint [1] 0 0
Mid-February 2021 (Approximately 2 years after study initiation)
Secondary outcome [1] 0 0
ORR
Timepoint [1] 0 0
Approximately 2 years after study initiation.
Secondary outcome [2] 0 0
PFS
Timepoint [2] 0 0
Approximately 2 years after study initiation.
Secondary outcome [3] 0 0
Severe Neutropenia
Timepoint [3] 0 0
Day 8 of Cycle 1
Secondary outcome [4] 0 0
Month 24 OS Rate
Timepoint [4] 0 0
24-month after study initiation
Secondary outcome [5] 0 0
Month 36 OS Rate
Timepoint [5] 0 0
36 month after study initiation
Secondary outcome [6] 0 0
DoR
Timepoint [6] 0 0
Approximately 2 years after study initiation.
Secondary outcome [7] 0 0
Quality of Life (EORTC QLQ-C30)
Timepoint [7] 0 0
Approximately 2 years after study initiation.
Secondary outcome [8] 0 0
Q-TWiST
Timepoint [8] 0 0
Approximately 2 years after study initiation.
Secondary outcome [9] 0 0
QoL (QLQ-LC13)
Timepoint [9] 0 0
Approximately 2 years after study initiation.
Secondary outcome [10] 0 0
Proportion of patients who received docetaxel
Timepoint [10] 0 0
During 1st 21-day cycle
Secondary outcome [11] 0 0
Month 18 OS Rate
Timepoint [11] 0 0
18 month after study initiation
Secondary outcome [12] 0 0
RDI
Timepoint [12] 0 0
First 4, 6, 8, 10, and 12 cycles
Secondary outcome [13] 0 0
Month 12 OS Rate
Timepoint [13] 0 0
12 month after study initiation

Eligibility
Key inclusion criteria
INCLUSION CRITERIA:

1. Males and females = 18 years of age
2. ECOG performance status = 2.
3. Histopathologically or cytologically confirmed non-squamous or squamous NSCLC.
4. Disease progression during or after treatment with one or two treatment regimen(s) Treatment regimens can be chemotherapy, targeted therapy, biological therapy, or immunotherapy for advanced (Stage IIIB) or metastatic disease (Stage IV). Modification of a regimen to manage toxicity with a different drug does not constitute a new regimen. Maintenance therapy following platinum-based chemotherapy is not considered as a separate regimen. Adjuvant or neoadjuvant chemotherapy and/or chemo-radiation for early stage disease do not count as prior systemic therapy. Prior radiation therapy is not exclusionary. Prior immunotherapy with a PD-1/PD-L1 inhibitor is not exclusionary. Prior treatment for advanced or metastatic disease must have included a platinum-based regimen. (Treatment of early stage disease [Stage IIIA or earlier] with a platinum-containing therapy does not count).
5. 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;
6. 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;
7. 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.
8. 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;
9. 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;
10. Life expectancy more than 12 weeks;
11. Female patients of childbearing potential have a negative pregnancy test at baseline. 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 amenorrheic 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.

1. 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.
2. 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.
3. For male patients who are sexually active and who are partners of premenopausal women: agreement to use two forms of contraception as in criterion 11b above during the treatment period and for at least 3 months after the last dose of study drug.
12. Signed informed consent.

EXCLUSION CRITERIA: Patients with any of the following:

1. 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.
2. 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.
3. Patients who have received prior treatment with docetaxel.
4. 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.
5. 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.
6. Active uncontrolled bacterial, viral, or fungal infection requiring systemic therapy.
7. Known infection with human immunodeficiency virus (HIV) or active hepatitis A, B, or C.
8. Known prior hypersensitivity reaction to any product containing polysorbate 80, polyoxyethylene 15 hydroxystearate/Macrogol 15 hydroxystearate (Solutol HS 15/ Kolliphor HS 15).
9. Female subject who is pregnant or lactating.
10. Second malignancy unless in remission for >5 years. (Non-melanoma skin cancer or carcinoma in situ of the cervix treated with curative intent is not exclusionary).
11. Any medical conditions that, in the Investigator's opinion, would impose excessive risk to the patient. Examples of such conditions include uncontrolled diabetes, infection requiring parenteral anti-infective treatment, liver failure, any altered mental status or any psychiatric condition that would interfere with the understanding of the informed consent form.
12. Unwilling or unable to comply with procedures required in this protocol.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/12/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
23/05/2021
Sample size
Target
Accrual to date
Final
559
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
Blacktown Cancer Centre - Blacktown
Recruitment hospital [2] 0 0
Border Medical Oncology Research Unit - East Albury
Recruitment hospital [3] 0 0
Gosford Hospital - Gosford
Recruitment hospital [4] 0 0
Adult Mater Hospital - South Brisbane
Recruitment hospital [5] 0 0
Peninsula and South East Oncology - Melbourne
Recruitment hospital [6] 0 0
Epworth Hospital - Richmond
Recruitment hospital [7] 0 0
Fiona Stanley Hospital - Murdoch
Recruitment hospital [8] 0 0
Perth Oncology/Mount Hospital - Perth
Recruitment hospital [9] 0 0
St John of God Hospital, Subiaco - Subiaco
Recruitment postcode(s) [1] 0 0
2148 - Blacktown
Recruitment postcode(s) [2] 0 0
2640 - East Albury
Recruitment postcode(s) [3] 0 0
2250 - Gosford
Recruitment postcode(s) [4] 0 0
4101 - South Brisbane
Recruitment postcode(s) [5] 0 0
3199 - Melbourne
Recruitment postcode(s) [6] 0 0
3121 - Richmond
Recruitment postcode(s) [7] 0 0
6150 - Murdoch
Recruitment postcode(s) [8] 0 0
6000 - Perth
Recruitment postcode(s) [9] 0 0
6008 - Subiaco
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Connecticut
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Kansas
Country [8] 0 0
United States of America
State/province [8] 0 0
Kentucky
Country [9] 0 0
United States of America
State/province [9] 0 0
Michigan
Country [10] 0 0
United States of America
State/province [10] 0 0
Mississippi
Country [11] 0 0
United States of America
State/province [11] 0 0
Missouri
Country [12] 0 0
United States of America
State/province [12] 0 0
North Carolina
Country [13] 0 0
United States of America
State/province [13] 0 0
Ohio
Country [14] 0 0
United States of America
State/province [14] 0 0
Pennsylvania
Country [15] 0 0
United States of America
State/province [15] 0 0
Tennessee
Country [16] 0 0
China
State/province [16] 0 0
Anhui
Country [17] 0 0
China
State/province [17] 0 0
Beijing
Country [18] 0 0
China
State/province [18] 0 0
Fujian
Country [19] 0 0
China
State/province [19] 0 0
Guizhou
Country [20] 0 0
China
State/province [20] 0 0
Hebei
Country [21] 0 0
China
State/province [21] 0 0
Heilongjiang
Country [22] 0 0
China
State/province [22] 0 0
Henan
Country [23] 0 0
China
State/province [23] 0 0
Hunan
Country [24] 0 0
China
State/province [24] 0 0
Jiangsu
Country [25] 0 0
China
State/province [25] 0 0
Jiangxi
Country [26] 0 0
China
State/province [26] 0 0
Jilin
Country [27] 0 0
China
State/province [27] 0 0
Liaoning
Country [28] 0 0
China
State/province [28] 0 0
Shaanxi
Country [29] 0 0
China
State/province [29] 0 0
Shangdong
Country [30] 0 0
China
State/province [30] 0 0
Shanghai
Country [31] 0 0
China
State/province [31] 0 0
Sichuan
Country [32] 0 0
China
State/province [32] 0 0
Tianjin
Country [33] 0 0
China
State/province [33] 0 0
Xinjiang
Country [34] 0 0
China
State/province [34] 0 0
Zhejiang

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
BeyondSpring Pharmaceuticals Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT02504489