TerminatedNCT02826161CanStem43LUpdated Nov 15, 2023Results posted

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

A Phase 3 interventional study of Napabucasin and Paclitaxel in Carcinoma, Non-Small-Cell Lung, sponsored by Sumitomo Pharma America, Inc.. Terminated at 5 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-11-15.

Sponsored by Sumitomo Pharma America, Inc. (part of Sumitomo Pharma Co., Ltd.) · Phase 3, Interventional, and Treatment

Why this study was terminated

Change of treatment landscape and evolving standard of care

Phase: Phase 3
Study type: Interventional
Enrollment: 4
Allocation: Randomized
Ages: 18 Years and older
Sex: All

Study 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.

Conditions studied

Carcinoma, Non-Small-Cell Lung

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Keywords

Neoplasms
Neoplasms by Site
Lung Neoplasms
Thoracic Neoplasms
Respiratory Tract Neoplasms
Bronchial Neoplasms

In context

Carcinoma, Non-Small-Cell Lung

6,641 studies on the registry are indexed under Carcinoma, Non-Small-Cell Lung; 1,665 are open to participants now.

This study's enrollment of 4 is below the median of 62 across 5,327 interventional studies indexed under Carcinoma, Non-Small-Cell Lung.

Browse Carcinoma, Non-Small-Cell Lung studies →

Lead sponsor

Sumitomo Pharma America, Inc. is the lead sponsor of 181 studies on the registry; 5 are open to participants now.

Of its 33 completed or terminated interventional studies of FDA-regulated products, 21 (64%) have results posted.

First submitted after Sumitomo Pharma America, Inc. became part of Sumitomo Pharma Co., Ltd..

Browse Sumitomo Pharma America, Inc. studies →All Sumitomo Pharma Co., Ltd. studies →

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Eligibility criteria

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

Study design

Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 4 participants (actual)

Study arms

Experimental
Napabucasin plus Weekly 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.
Drug: Napabucasin · Drug: Paclitaxel
Active comparator
Weekly Paclitaxel
Patients randomized to this arm will receive weekly paclitaxel alone administered intravenously, once weekly, on 3 of every 4 weeks.
Drug: Paclitaxel

Interventions

DrugNapabucasin
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.
Also known as: BBI-608, BBI608, BB608
DrugPaclitaxel
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.

What researchers measure

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
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.
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
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.
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

Results

Posted Jun 15, 2021

Limitations and caveats

On 12 June 2017 the sponsor notified study investigator that the study was terminated because of the rapidly evolving standard of care for patients with NSCLC. At the time of the termination, there were only 4 patients randomized (3 to the control arm and 1 to the napabucasin arm). Due to the small sample size, neither safety or efficacy data were analyzed or summarized for this study.

Participant flow

Participant flow — Overall Study
Milestone	Napabucasin Plus Paclitaxel	Paclitaxel Only
Started	1	3
Discontinued due to treatment related ae	1	0
Discontinued due to death	0	1
Discontinued due to patient withdrawal	0	1
Discontinued due to withdrawal of icf from further fu	1	1
Completed	1	3
Not completed	0	0

Outcome measures

PrimaryOverall 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