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Assessment of Docetaxel + Plinabulin Compared to Docetaxel + Placebo in Patients With Advanced NSCLC With at Least One Measurable Lung Lesion (DUBLIN-3)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2016 by BeyondSpring Pharmaceuticals Inc.
Sponsor:
Information provided by (Responsible Party):
BeyondSpring Pharmaceuticals Inc.
ClinicalTrials.gov Identifier:
NCT02504489
First received: July 16, 2015
Last updated: March 17, 2017
Last verified: July 2016
  Purpose

The primary purpose of the study is to compare the overall survival of NSCLC patients receiving second- or third-line chemotherapy with docetaxel + plinabulin (DP Arm) to patients treated with docetaxel + placebo (D Arm) for advanced or metastatic disease.

Secondary purposes of the study are:

  1. To compare the neutropenia (frequency, severity and clinical sequelae), duration of response, quality of life, response rate and progression free survival in patients with NSCLC treated with DP to patients treated with D as second- or third-line chemotherapy for advanced or metastatic disease; and
  2. To compare the safety and adverse event profiles of DP to D respectively, as well as dose delays, dose modifications, and/or dose discontinuation of docetaxel due to safety concerns in the two treatment arms.
  3. To evaluate population pharmacokinetics in patients enrolled in China and western countries (US and Australia).

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

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
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

Resource links provided by NLM:


Further study details as provided by BeyondSpring Pharmaceuticals Inc.:

Primary Outcome Measures:
  • Overall Survival [ Time Frame: Approximately 2 years after study initiation ]

Secondary Outcome Measures:
  • Progression free survival [ Time Frame: Approximately 2 years after study initiation. ]
  • Response rate [ Time Frame: Approximately 2 years after study initiation. ]
  • Duration of response [ Time Frame: Approximately 2 years after study initiation. ]
  • Incidence and severity of treatment-emergent adverse events [ Time Frame: Approximately 2 years after study initiation. ]
  • Incidence of serious adverse events. [ Time Frame: Approximately 2 years after study initiation. ]
  • Incidence of discontinuation of study treatment due to safety reasons [ Time Frame: Approximately 2 years after study initiation. ]

Estimated Enrollment: 550
Study Start Date: June 2016
Estimated Study Completion Date: April 2019
Estimated Primary Completion Date: November 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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 30 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.

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

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
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 regiments can be chemotherapy or immunotherapy for advanced (Stage IIIB) or metastatic disease (Stage IV). Modification of 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 chemotherapy and/or chemoradiation for early stage disease do not count as prior chemotherapy. Prior radiation and/or PD-1/PD-L1 immunotherapy is not exclusionary. Prior treatment for advanced or metastatic disease must have included a platinum-based regimen.
  4. At least 1 lesion > 3 cm 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. Patients without EGFR sensitizing mutations are eligible and must have progressed on platinum-containing chemo.
  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 enrollment
  7. All AE's of prior chemo., 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 1.5x109/L independent of growth factor support; platelet count 100x109/L independent of transfusion or growth factor support; Serum total bilirubin 1.5 times the upper limit normal (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. 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, paclitaxel or other taxane preparation for advanced or metastatic disease.
  4. Prior transient ischemic attack or cerebrovascular accident. Neurologic toxicities > Grade 2.
  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: 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02504489

Contacts
Contact: Lan Huang, Ph.D. 1 (646)528-4184 lhuang@beyondspringpharma.com
Contact: Gordon L Schooley, Ph.D. 1 (858) 353-0704 gschooley@beyondspringpharma.com

Locations
United States, California
Pacific Cancer Medical Center, Inc. Recruiting
Anaheim, California, United States, 92801
Contact: Elizabeth Brown       elizabethg@pacificcancer.com   
Principal Investigator: Veena Charu, MD         
U. California San Diego (UCSD) Moores Cancer Center Recruiting
La Jolla, California, United States, 92093
Contact: Lyudmila A. Bazhenova, M.D.    858-822-6100    lbazhenova@ucsd.edu   
UC San Diego Moores Cancer Center Recruiting
La Jolla, California, United States, 92093
Contact: Justine Panian    858-534-7585    japanian@ucsd.edu   
Principal Investigator: Lyudmila Bazhenova, MD         
NICR: Synergy Hematology Oncology Recruiting
Los Angeles, California, United States, 90048
Contact: Anton Akulov    323-725-0657    aakulov@nicresearch.com   
Principal Investigator: Levon Qasabian, MD         
Innovative Clinical Research Institute Recruiting
Whittier, California, United States
Contact: Kirsten Bettino       kbettino@airesearch.us   
Principal Investigator: Eddie Thara, MD         
United States, Colorado
Memorial Health Care System Recruiting
Colorado Springs, Colorado, United States
Contact: Caralyn Hutchens       caralyn.henderson@uchealth.org   
Principal Investigator: Robert Hoyer, MD         
United States, Georgia
Peachtree Hematoloy-Oncology Consultants, PC Recruiting
Atlanta, Georgia, United States
Contact: Ann Johnston       AJohnston@piedmontcancerinstitute.com   
Principal Investigator: Trevor Feinstein, MD         
United States, Illinois
Carle Cancer Center Recruiting
Urbana, Illinois, United States, 61801
Contact: Joshua Ward       joshua.ward@carle.com   
Principal Investigator: Krishna Vasireddy, DO         
United States, Kentucky
University of Louisville-Brown Cancer Center Recruiting
Louisville, Kentucky, United States, 40202
Contact: Goetz Kloecker, MD       goetz.kloecker@louisville.edu   
Contact: Karen Carter, RN       k.carter@louisville.edu   
United States, Mississippi
Hattiesburg Clinic Hematology/Oncology Recruiting
Hattiesburg, Mississippi, United States, 39401
Contact: Tammy McBeth    601-288-2495    tmcbeth@forrestgeneral.com   
Principal Investigator: John Hrom, MD         
United States, Ohio
University of Cincinnati Not yet recruiting
Cincinnati, Ohio, United States, 45267
Contact: Nagia A Karim, MD       karimnf@uc.edu   
Toledo Cancer Center Recruiting
Toledo, Ohio, United States, 43623
Contact: Rex B Mowat, MD    419-473-3561      
Contact: Jessica Ciesler, RN    419-473-3561      
United States, Tennessee
Cookeville Regional Medical Center Cancer Center Recruiting
Cookeville, Tennessee, United States, 61801
Contact: Linda Moore       lamoore@crmchealth.org   
Principal Investigator: Paul Jacquin, MD         
Sponsors and Collaborators
BeyondSpring Pharmaceuticals Inc.
Investigators
Principal Investigator: Lyudmila A Bazhenova, M.D. U. California San Diego (UCSD) Moores Cancer Center 858-822-6100
  More Information

Additional Information:
Responsible Party: BeyondSpring Pharmaceuticals Inc.
ClinicalTrials.gov Identifier: NCT02504489     History of Changes
Other Study ID Numbers: BPI-2358-103
Study First Received: July 16, 2015
Last Updated: March 17, 2017
Individual Participant Data  
Plan to Share IPD: No

Additional relevant MeSH terms:
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
Docetaxel
Diketopiperazines
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Anti-Bacterial Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on April 24, 2017