Active Clinical Trials
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
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:
- 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
- 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.
- To evaluate population pharmacokinetics in patients enrolled in China and western countries (US and Australia)
Ages Eligible for Study:
18 Years and older (Adult, Senior)
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- ECOG performance status ≤ 2.
- Histopathologically or cytologically confirmed NSCLC.
- 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.
- At least 1 lesion > 3 cm in longest diameter in lung parenchyma.
- 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.
- 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.
- 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.
- 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;
- 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.
- Life expectancy >12 weeks.
- Signed informed consent.
EXCLUSION CRITERIA: Patients with any of the following:
- 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.
- 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
- Patients who have received prior treatment with docetaxel, paclitaxel or other taxane preparation for advanced or metastatic disease.
- Prior transient ischemic attack or cerebrovascular accident. Neurologic toxicities > Grade 2.
- 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).
- Female subject who is pregnant or lactating
- 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.)
- 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.
- Unwilling or unable to comply with protocol.