Histologically or cytologically confirmed recurrent, locally advanced, or metastatic non-squamous non-small cell lung cancer. MedDRA version: 21.1 Level: LLT Classification code 10066490 Term: Progression of non-small cell lung cancer System Organ Class: 100000004864
Conditions
Interventions
Product Name: BBI-608 (napabucasin)
Product Code: BBI-608
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Napabucasin
CAS Number: 83280-65-3
Current Sponsor code: -
Other descriptive name: NAP
Sponsors
BOSTON BIOMEDICAL, INC.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: IC 1 Must have histologically or cytologically confirmed non-squamous NSCLC. Patients with mixed histology must have adenocarcinoma as the predominant morphology according to light microscopy pathologic diagnosis. Patients with poorly differentiated tumors must have immunohistochemical (IHC) staining positive for either TTF-1 or NapsinA and negative for p63 or p40. IC 2 Patients with an EGFR or ALK/ROS1 genetic aberration must have received appropriately targeted treatment. IC 3 Must have progressed following treatment with platinum-based combination chemotherapy for metastatic disease. (...) IC 4 Patients who are candidates for immunotherapy must have received either nivolumab or pembrolizumab or a different IND-approved anti-PD1 or anti-PD-L1 therapy. IC 5 Prior treatment with the approved agents such as pemetrexed and/or erlotinib is permitted, and candidates who have not received a prior approved regimen must be informed that enrollment onto the trial may delay or prevent treatment that has shown a survival benefit in randomized trials. IC 6 Weekly paclitaxel must be an acceptable treatment option IC 7 Must have had resolution to Grade = 1 of all clinically significant adverse events from prior therapy, (grade defined according to the National Cancer Institute Common Terminology Criteria for Adverse Events [NCI-CTCAE]); or, the adverse events must be deemed irreversible, and considered not an impediment to participation in the trial according to the investigator. IC 8 Must have had baseline radiologic imaging evaluation of the chest, abdomen, and pelvis in the 21 days prior to randomization that documents the presence of measurable or non-measurable disease as defined by RECIST 1.1 IC 9 Must submit tumor tissue for correlative analyses IC 10 Must allow collection and storage of blood samples for correlative analyses IC 11 Must be at least 18 years of age IC 12 Must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 IC 13 Must be willing and able to take BBI-608 orally IC 14 Must have total bilirubin = 1.5 x upper limit of normal (ULN) IC 15 Must have aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 2.5 x ULN; or must have AST and ALT = 5 x ULN if the aminotransferase elevation is due to liver metastases IC 16 Must have estimated creatinine clearance = 50 mL/min as calculated following a 24 hour urine collection or by using the Cockcroft-Gault formula (Cockcroft-Gault estimation of creatinine clearance = [140-age] * [Wt in kg] * [(0.85 if female) vs (1.0 if male)] / [72 * Cr] where “Cr” is serum creatinine in mg/dl); or, IC 16a Must have estimated creatinine clearance (eCrCl) = 50 mL/min when corrected for body surface area (in m2) as follows: Corrected estimated creatinine clearance (eCrClcorrected) = (eCrCl) x 1.73 / patient BSA IC 17 Must have absolute neutrophil count (ANC) = 1.5 x 103/µL (= 1.5 x 109/L) IC 18 Must have hemoglobin = 9.0 g/dL without transfusion in the prior 7 days IC 19 Must have platelets =100 x 103/µL (=100 x 109/L) without transfusion in the prior 7 days IC 20 Must have serum albumin = 3.0 g/dL IC 21 Must have Body Mass Index (BMI) > 18.5 kg/m2 IC 22 Must have a life expectancy of = 3 months IC 23 Must be able (i.e. sufficiently fluent) and willing to complete the Quality of Life questionnaires in one of the validated languages for the questionnaires; (...) IC 24 Patients must be accessible for treatment and follow-up. (...) IC 25
Exclusion criteria
Exclusion criteria: EC 1 Have squamous sub-type NSCLC as identified by histologic morphology using light microscopy; or, EC 1a NSCLC with a mixed histologic morphology suggesting a predominance of squamous features; or, EC 1b NSCLC with poorly differentiated histologic morphology not meeting IC 1 EC 2 Has received systemic treatment with a taxane for advanced/metastatic disease. Patients are also excluded if there was disease progression or recurrence less than 6 months after adjuvant, neo-adjuvant or chemo-radiation therapy that contained a taxane. EC 3 Has received any systemic anti-cancer therapy within the 14 days prior to randomization EC 4 Has received radiotherapy within the 28 days prior to randomization, with the exception of palliative radiotherapy to focal lesions for pain or other symptom control up to 8 gy (800 rad) EC 5 Has brain metastases with evolving neurologic symptoms or a steroid requirement. Patients with brain metastases who are clinically stable and who do not require steroids may be eligible. Patients with known leptomeningeal metastases are excluded, even if treated or asymptomatic EC 6 Has had major surgery requiring general anesthesia and/or mechanical ventilation within the 28 days prior to randomization; or, intends to have an elective surgical procedure during the course of planned study participation that carries risk other than minimal discomfort. A biopsy is not considered major surgery. EC 7 Has hypersensitivity to paclitaxel despite re-sensitization procedures or has history of severe hypersensitivity to any paclitaxel excipient, including macrogolglycerol ricinoleate. EC 8 Has a concurrent malignancy except for basal or squamous cell skin cancer and/or in situ carcinoma of the cervix, or other solid tumors treated curatively and without evidence of recurrence for at least 3 years prior to randomization EC 9 Has had extensive colonic or small bowel resection such that absorption of oral medications is considered impaired EC 10 Has known hepatitis B with clinical complications (patients with chronic, controlled, hepatitis B with or without anti-viral therapy and monitored according to 2015 ASCO guideline for hepatitis B monitoring may be eligible) EC 11 Is currently receiving interferon for known hepatitis C; or has clinically uncontrolled hepatitis C or hepatitis C with significant complications likely to interfere with protocol compliance. EC 12 Has known human immunodeficiency virus (HIV) infection, acquired immunodeficiency syndrome (AIDS), or an AIDS-related/AIDS-defining illness EC 13 Has had a myocardial infarction, unstable angina, stroke, transient ischemic attack, or other major vascular complication in the 6 months prior to randomization EC 14 Has clinically relevant congestive heart failure (CHF; NYHA II-IV) EC 15 Has a corrected QT interval (QTc) > 470 ms or has an electrocardiogram (ECG) with a new abnormal finding that is clinically significant. Patients with a known cardiac arrhythmia that is adequately controlled and not affecting performance status, such as atrial fibrillation, may be eligible. Patients with a pacemaker and no major complications (hospitalization, infection) in the 6 months prior to randomization may be eligible EC 16 Has active inflammatory enteropathy, Crohn's disease, ulcerative colitis, or other chronic diarrheal illness that is not adequately controlled EC 17 Has peripheral neuropathy = Grade 2 (NCI-CTCAE). EC 18 Refuses to complete quality of life questionnaires
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare overall survival in patients with previously treated metastatic non-squamous non-small cell lung cancer (non-squamous NSCLC) who are randomized to receive treatment with BBI-608 plus weekly paclitaxel versus weekly paclitaxel alone.;Secondary Objective: ¿ To compare OS in patients with previously treated metastatic non-squamous NSCLC who are biomarker positive and who are randomized to receive treatment with BBI-608 plus weekly paclitaxel versus weekly paclitaxel alone. ¿ To compare progression free survival (PFS, defined as the time from randomization until disease progression per RECIST 1.1 or death) in patients with non-squamous NSCLC who are randomized to receive treatment with BBI-608 plus weekly paclitaxel versus weekly paclitaxel alone. ¿ To compare PFS in patients with non-squamous NSCLC who are biomarker positive and who are randomized to receive treatment with BBI-608 plus weekly paclitaxel versus weekly paclitaxel alone. Please refer to the protocol for further secondary objectives.;Primary end point(s): Overall Survival;Timepoint(s) of evaluation of this end point: The final analysis will occur when at least 694 events are observed by randomizing 870 patients over 24 months, with 12 months minimum follow-up for each patient.The sample size calculation assumes a dropout rate of up to 5% for the entire study. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): ¿ Overall Survival in the predefined biomarker-positive sub-population¿ ¿ Progression Free Survival in the ITT study population ¿ Progression Free Survival in the predefined biomarker-positive subpopulation¿ ¿ Disease Control Rate & Objective Response Rate in the ITT study population ¿ Disease Control Rate & Objective Response Rate in the predefined biomarker-positive sub-population¿ ¿ Quality of Life ¿ Safety Profile ¿The biomarker-positive sub-population is defined as those patients positive for phosphorylated STAT3 (p-STAT3) based on immunohistochemical (IHC) staining of Formalin-Fixed, ParaffinEmbedded (FFPE) tumor tissue.;Timepoint(s) of evaluation of this end point: Please refer to protocol for further information. | — |
Countries
Australia, Belgium, Canada, China, Czechia, France, Germany, Hungary, Israel, Italy, Japan, Korea, Republic of, Netherlands, Poland, Spain, United Kingdom, United States
Contacts
Public ContactClinical Division
Boston Biomedical, Inc.
Outcome results
None listed