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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT02504489
Ethics application status
Date submitted
16/07/2015
Date registered
21/07/2015
Date last updated
21/05/2018

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). Routine 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, plinabulin infusion will be repeated.
On Day 1, no pre-medication will be routinely administered for plinabulin infusion. Anti-emetics may be prescribed as indicated according to institutional guidelines for chemotherapy. On Day 8, antiemetic prophylaxis may be administered prior to plinabulin infusion. For Cycle 1 Day 8 only, Zofran® (ondansetron) is prohibited due to its interference with QTc study.


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 - 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.
Timepoint [1] 0 0
Approximately 2 years after study initiation
Secondary outcome [1] 0 0
To compare the Grade 4 neutropenia on Day 8 (+/- 1 day) of Cycle 1), DoR, neutrophil count on Day 8 (+/- 1 day) of Cycle 1, incidence of docetaxel dose reduction and/or docetaxel dose withheld in Cycle 2 due to neutropenia in Cycle 1, QoL ORR, and PFS - Comparisons between DP and D + placebo arms will be based on incidence of Grade 4 neutropenia on Day 8 of Cycle 1 (all data and by subgroups of tumor status)
Timepoint [1] 0 0
Approximately 2 years after study initiation.
Secondary outcome [2] 0 0
To compare the safety and adverse events profile of the DP Arm to D Arm. - compare the safety and adverse events profile of the DP Arm to D Arm.
Timepoint [2] 0 0
Approximately 2 years after study initiation.
Secondary outcome [3] 0 0
To compare dose intensity of docetaxel (percent dose administered compared to dose assigned) between the 2 treatment arms. - Dose intensity is the % of docetaxel actually administered compared to the planned dose of docetaxel per cycle compared between the 2 treatment arms
Timepoint [3] 0 0
Approximately 2 years after study initiation.
Secondary outcome [4] 0 0
To evaluate population pharmacokinetics in patients enrolled in the Western countries and China. - evaluate the effect of intrinsic and extrinsic factors on the PK of plinabulin and its active metabolite(s), if identified, in humans
Timepoint [4] 0 0
Approximately 2 years after study initiation.

Eligibility
Key inclusion criteria
INCLUSION CRITERIA:

1. ECOG performance status = 2.

2. Histopathologically or cytologically confirmed NSCLC.

3. 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).

4. At least 1 lesion =10 mm in longest diameter in lung parenchyma.

5. patients with nonsquamous NSCLC must have been tested for EGFR exon 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

6. 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.

7. All AE's of prior systemic therapy, surgery, or radiotherapy, must have resolved to
CTCAE v 4.03 Grade =2, except for neurological AE's that must have resolved to Grade
=1.

8. The following laboratory results =14 days prior to study drug admin:

Hgb =9 g/dL independent of transfusion or growth factor support; absolute neutrophil
count 1.5x10^9/L independent of growth factor support; platelet count =100x10^9/L
independent of transfusion or growth factor support; Serum total bilirubin = ULN,
unless the patient has a diagnosis of Gilbert's disease then serum bilirubin 3.0 times
ULN;

9. AST & ALT =2.5 x ULN(=1.5 x ULN if alkaline phosphatase is > 2.5 x ULN), and serum
creatinine =1.5 x ULN.

10. Life expectancy >12 weeks.

11. Female patients of childbearing potential have a negative pregnancy test at baseline.

12. Signed informed consent.

EXCLUSION CRITERIA: Patients with any of the following:

1. Administration of chemo, biological, immunotherapy, radiotherapy or investigational
agent (therapeutic or diagnostic) =3 weeks prior to receipt of study medication. Major
surgery, other than diagnostic surgery, =4 weeks before first study drug admin.

2. Significant cardiac history:

History of myocardial infarction or ischemic heart disease =1 year before 1st study
drug administration; uncontrolled arrhythmia; history of congenital QT prolongation;
ECG findings consistent with acute ischemic heart disease; NYHA Class III-IV cardiac
disease; & uncontrolled hypertension: BP consistently >150 mm Hg systolic & 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 with in the past year.
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).

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. Medical conditions that would impose excessive patient risk. Examples: uncontrolled
diabetes, infection requiring parenteral anti infective treatment, liver failure,
altered mental status or psychiatric condition that would interfere with the
understanding of the informed consent.

12. Unwilling or unable to comply with protocol.
Minimum age
18 Years
Maximum age
No limit
Gender
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
Open (masking not used)
Who is / are masked / blinded?



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

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
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
Barwon Health - Geelong
Recruitment hospital [6] 0 0
Peninsula and South East Oncology - Melbourne
Recruitment hospital [7] 0 0
Epworth Hospital - Richmond
Recruitment hospital [8] 0 0
Fiona Stanley Hospital - Murdoch
Recruitment hospital [9] 0 0
Perth Oncology/Mount Hospital - Perth
Recruitment hospital [10] 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
3220 - Geelong
Recruitment postcode(s) [6] 0 0
3199 - Melbourne
Recruitment postcode(s) [7] 0 0
3121 - Richmond
Recruitment postcode(s) [8] 0 0
6150 - Murdoch
Recruitment postcode(s) [9] 0 0
6000 - Perth
Recruitment postcode(s) [10] 0 0
6008 - Subiaco
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Kentucky
Country [6] 0 0
United States of America
State/province [6] 0 0
Mississippi
Country [7] 0 0
United States of America
State/province [7] 0 0
Ohio
Country [8] 0 0
United States of America
State/province [8] 0 0
Tennessee

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

Ethics approval
Ethics application status

Summary
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 the neutropenia (incidence of Grade 4 neutropenia [absolute neutrophil count
(ANC) < 0.5 × 10^9/L]) on Day 8 (+/- 1 day) of Cycle 1), DoR, neutrophil count on Day 8
(+/- 1 day) of Cycle 1, incidence of docetaxel dose reduction and/or docetaxel dose
withheld in Cycle 2 due to neutropenia in Cycle 1, QoL (EORTC QLQ-C30 [item 30, average
overall quality of life over all observable weeks]), ORR, and PFS in patients with NSCLC
treated in the DP Arm to patients treated in the D Arm as 2nd- or 3rd-line therapy for
advanced or metastatic disease.

- To compare the safety and adverse events profile of the DP Arm to D Arm.

- To compare dose intensity of docetaxel (percent dose administered compared to dose
assigned) between the 2 treatment arms.

- To evaluate population pharmacokinetics in patients enrolled in the Western countries
and China.
Trial website
https://clinicaltrials.gov/show/NCT02504489
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
Ramon Mohanlal, M.D.
Address 0 0
Country 0 0
Phone 0 0
1 (646)305-6387
Fax 0 0
Email 0 0
rmohanlal@beyondspringpharma.com
Contact person for scientific queries

No data has been provided for results reporting
Summary results
Not applicable