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

Phase 3TerminatedNCT02826161

Sumitomo Pharma America, Inc.4 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: * 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 Exclusion Criteria: * 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

Locations (5)

Unnamed facility

Beverly Hills, California, United States

Unnamed facility

Santa Rosa, California, United States

Unnamed facility

Aventura, Florida, United States

Unnamed facility

Gettysburg, Pennsylvania, United States

Unnamed facility

Arlington, Texas, United States

Outcomes

Primary Outcomes

Overall Survival

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.

Time frame: 36 months

Secondary Outcomes

Overall Survival in Biomarker Positive Patients

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.

Time frame: 36 months

Progression Free Survival

Time frame: 36 months

Progression Free Survival in Biomarker Positive Patients

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.

Time frame: 36 months

Disease Control Rate in Biomarker Positive Patients

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.

Time frame: 36 months

Quality of Life (QoL)

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.

Time frame: 36 months

Disease Control Rate

Time frame: 36 months

Number of Patients With Adverse Events

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.

Time frame: 36 months