A Study of Napabucasin (BBI-608) Plus Weekly Paclitaxel Versus Weekly Paclitaxel Alone in Patients With Advanced, Previously Treated, Non-Squamous Non-Small Cell Lung Cancer
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Interventions
- Registration Number
- NCT02826161
- Lead Sponsor
- Sumitomo Pharma America, Inc.
- Brief Summary
This is an international, multi-center, prospective, randomized, open-label Phase 3 clinical trial of the cancer stemness inhibitor napabucasin administered with weekly paclitaxel versus weekly paclitaxel alone in patients with advanced non-squamous non-small cell lung cancer who have disease progression following systemic treatment with a platinum-based combination regimen in the metastatic setting, who have received treatment with an immune checkpoint inhibitor if a candidate, additional approved therapies, and for whom weekly paclitaxel is an acceptable treatment option.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 4
- Must have histologically or cytologically confirmed non-squamous NSCLC.
- Must have progressed following treatment with platinum-based combination chemotherapy for metastatic disease, and patients with an EGFR or ALK/ROS1 genetic aberration must have received appropriately targeted treatment.
- Must have received either nivolumab or pembrolizumab or a different IND-approved anti-PD1 or anti-PD-L1 therapy, unless medically contraindicated
- Weekly paclitaxel must be an acceptable treatment option
- Must submit tumor tissue for correlative analyses
- Women of child-bearing potential and partners of women of child-bearing potential must take measures to avoid pregnancy while receiving and for a period of time following protocol therapy
- Must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, adequate organ function, and a life expectancy of ≥ 3 months
Key
- Has squamous NSCLC
- Has received prior systemic treatment with a taxane for advanced/metastatic disease
- Has received systemic anti-cancer therapy within the 14 days prior to randomization
- 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
- Has brain metastases with evolving neurologic symptoms or a steroid requirement.
- Has had major surgery requiring general anesthesia and/or mechanical ventilation within the 28 days prior to randomization
- Has a corrected QT interval (QTc) > 470 ms or has an electrocardiogram (ECG) with a new abnormal finding that is clinically significant
- Has peripheral neuropathy ≥ Grade 2 (NCI-CTCAE)
- Refuses to complete quality of life questionnaires either alone or with assistance from study staff despite adequate fluency
- Has an intercurrent (non-malignant) chronic medical or psychiatric illness or condition(s) not optimally controlled and carrying a moderate to high risk of interfering with protocol therapy administration or compliance with required procedures, in the judgment of the investigator
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Napabucasin plus Weekly Paclitaxel Napabucasin Patients randomized to this arm will receive napabucasin administered orally, twice daily in combination with paclitaxel administered intravenously, once weekly, on 3 of every 4 weeks. Napabucasin plus Weekly Paclitaxel Paclitaxel Patients randomized to this arm will receive napabucasin administered orally, twice daily in combination with paclitaxel administered intravenously, once weekly, on 3 of every 4 weeks. Weekly Paclitaxel Paclitaxel Patients randomized to this arm will receive weekly paclitaxel alone administered intravenously, once weekly, on 3 of every 4 weeks.
- Primary Outcome Measures
Name Time Method Overall Survival 36 months To assess the effect of napabucasin plus weekly paclitaxel versus weekly paclitaxel on the Overall Survival of patients with previously treated advanced, non-squamous non-small cell lung cancer.
- Secondary Outcome Measures
Name Time Method Disease Control Rate 36 months To assess the effect of napabucasin plus weekly paclitaxel versus weekly paclitaxel on the Disease Control Rate (DCR) of patients with previously treated advanced, non-squamous non-small cell lung cancer. DCR is defined as the proportion of patients with a documented complete response, partial response, and stable disease (CR + PR + SD) based on RECIST 1.1.
Overall Survival in Biomarker Positive Patients 36 months To assess the effect of napabucasin plus weekly paclitaxel versus weekly paclitaxel on the Overall Survival of patients with previously treated advanced, non-squamous non-small cell lung cancer in biomarker positive patients. This biomarker-positive sub-population is defined as those patients with phospho-STAT3 based on immunohistochemical (IHC) staining of Formalin Fixed Paraffin Embedded (FFPE) tumor tissue.
Progression Free Survival in Biomarker Positive Patients 36 months To assess the effect of napabucasin plus weekly paclitaxel versus weekly paclitaxel on the Progression Free Survival (PFS) of patients with previously treated advanced, non-squamous non-small cell lung cancer in biomarker positive patients. PFS is defined as the time from randomization to the first objective documentation of disease progression or death due to any cause. This biomarker-positive sub-population is defined as those patients with phospho-STAT3 based on immunohistochemical (IHC) staining of Formalin Fixed Paraffin Embedded (FFPE) tumor tissue.
Progression Free Survival 36 months To assess the effect of napabucasin plus weekly paclitaxel versus weekly paclitaxel on the Progression Free Survival (PFS) of patients with previously treated advanced, non-squamous non-small cell lung cancer. PFS is defined as the time from randomization to the first objective documentation of disease progression or death due to any cause.
Disease Control Rate in Biomarker Positive Patients 36 months To assess the effect of napabucasin plus weekly paclitaxel versus weekly paclitaxel on the Disease Control Rate (DCR) of patients with previously treated advanced, non-squamous non-small cell lung cancer. DCR is defined as the proportion of patients with a documented complete response, partial response, and stable disease (CR + PR + SD) based on RECIST 1.1. This biomarker-positive sub-population is defined as those patients with phospho-STAT3 based on immunohistochemical (IHC) staining of Formalin Fixed Paraffin Embedded (FFPE) tumor tissue.
Quality of Life (QoL) 36 months QoL will be measured using the European Organization for Research and Treatment of Cancer Quality of Life questionnaire (EORTC-QLQ-C30) in patients with previously treated advanced, non-squamous non-small cell lung cancer with napabucasin plus weekly paclitaxel versus weekly paclitaxel.
Number of Patients With Adverse Events 36 months All patients who have received at least one dose of napabucasin will be included in the safety analysis according to the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) version 4.0. The incidence of adverse events will be summarized by type of adverse event and severity.