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

Carcinoma, Non-Small-Cell Lung Clinical Trial

— CanStem43L  

Official title:

A Phase III Randomized, Open-Label Clinical Trial of BBI-608 Plus Weekly Paclitaxel Versus Weekly Paclitaxel Alone in Patients With Advanced, Previously Treated, Non-Squamous Non-Small Cell Lung Cancer

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02826161
• Other study ID #: CanStem43L
• Status: Terminated
• Phase: Phase 3
• Start date: November 2016
• Est. completion date: April 24, 2017

Study information

• Verified date: November 2023
• Source: Sumitomo Pharma America, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 4
• Est. completion date: April 24, 2017
• Est. primary completion date: April 24, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung

Intervention

Drug:
• Napabucasin
Napabucasin will be administered in continuous 28-day cycles. The starting dose of napabucasin is 240 mg twice daily (480 mg total daily dose) with approximately 12 hours between each dose. Napabucasin should be taken with fluids either 1 hour prior to a meal or 2 hours after a meal.
• Paclitaxel
Paclitaxel will be administered intravenously, once weekly, via one-hour infusion at a starting dose-level of 80 mg/m^2 body surface area. The weekly paclitaxel infusion will be given during 3 out of every 4 weeks, on days 1, 8, and 15 of each 28-day study cycle.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Sumitomo Pharma America, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	36 months
Secondary	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.	36 months
Secondary	Progression Free Survival	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.	36 months
Secondary	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.	36 months
Secondary	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.	36 months
Secondary	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.	36 months
Secondary	Disease Control Rate	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.	36 months
Secondary	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.	36 months