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Docetaxel + Plinabulin Compared to Docetaxel + Placebo in Patients With Advanced NSCLC (DUBLIN-3)

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ClinicalTrials.gov Identifier: NCT02504489
Recruitment Status : Recruiting
First Posted : July 22, 2015
Last Update Posted : June 4, 2019
Sponsor:
Information provided by (Responsible Party):
BeyondSpring Pharmaceuticals Inc.

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 China and rest of world (RoW).

Condition or disease Intervention/treatment Phase
Non-Small Cell Lung Cancer Drug: Docetaxel + Plinabulin (DP) Drug: Docetaxel (D) Phase 3

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 554 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Masking Description: placebo
Primary Purpose: Treatment
Official 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
Actual Study Start Date : December 2015
Estimated Primary Completion Date : October 2019
Estimated Study Completion Date : November 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Docetaxel

Arm Intervention/treatment
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.
Drug: Docetaxel (D)
Docetaxel 75 mg/m2 IV
Other Name: Taxotere

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.
Drug: Docetaxel + Plinabulin (DP)
Docetaxel 75 mg/m2 IV + Plinabulin 30 mg/m2
Other Name: BPI-2358, NPI-2358

Drug: Docetaxel (D)
Docetaxel 75 mg/m2 IV
Other Name: Taxotere




Primary Outcome Measures :
  1. Overall Survival [ Time Frame: Approximately 2 years after study initiation ]
    Overall survival of NSCLC patients receiving 2nd- or 3rd-line systemic therapy


Secondary Outcome Measures :
  1. Grade 4 neutropenia [ Time Frame: During 1st 21-day cycle ]
    Incidence of Grade 4 neutropenia on Day 8 of Cycle 1

  2. Neutrophil count [ Time Frame: During 1st 21-day cycle ]
    Neutrophil count on Day 8 of Cycle 1

  3. docetaxel dose reduction and/or docetaxel dose withheld [ Time Frame: During 2nd 21-day cycle ]
    incidence of docetaxel dose reduction and/or docetaxel dose withheld in Cycle 2 due to neutropenia in Cycle 1

  4. Quality of Life (EORTC QLQ-C30) [ Time Frame: Approximately 2 years after study initiation. ]
    Average Quality of Life score over all observed weeks (scale 0 - 30, higher value represents better outcome)

  5. ORR [ Time Frame: Approximately 2 years after study initiation. ]
    Overall response rate

  6. PFS [ Time Frame: Approximately 2 years after study initiation. ]
    Progress-free survival

  7. DoR [ Time Frame: Approximately 2 years after study initiation. ]
    Duration of response



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 lung lesion ≥10 mm by CT or MRI per RECIST 1.1 criteria. Radiographic tumor assessment is to be performed within 28 days prior to randomization.
  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. 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.
  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(within an 18-day window). 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02504489


Contacts
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Contact: Ramon Mohanlal, M.D. 1 (646)305-6387 rmohanlal@beyondspringpharma.com
Contact: Gordon L Schooley, Ph.D. 1 (858) 353-0704 gschooley@beyondspringpharma.com

  Show 57 Study Locations
Sponsors and Collaborators
BeyondSpring Pharmaceuticals Inc.

Additional Information:
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Responsible Party: BeyondSpring Pharmaceuticals Inc.
ClinicalTrials.gov Identifier: NCT02504489     History of Changes
Other Study ID Numbers: BPI-2358-103
First Posted: July 22, 2015    Key Record Dates
Last Update Posted: June 4, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Diketopiperazines
Docetaxel
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Anti-Bacterial Agents
Anti-Infective Agents