Carcinoma, Non-Small-Cell Lung
Conditions
Keywords
Neoplasms, Neoplasms by Site, Lung Neoplasms, Thoracic Neoplasms, Respiratory Tract Neoplasms, Bronchial Neoplasms
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.
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.
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.
Sponsors
Sumitomo Pharma America, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Napabucasin Plus Paclitaxel All participants randomized to receive napabucasin (BBI-608) 240 mg twice daily administered orally, twice daily (480 mg total in a day) plus Paclitaxel 80 mg/m2 IV; once weekly ( three out of every four weeks) | 1 |
| Paclitaxel Only All participants randomized to receive Paclitaxel 80 mg/m2 IV, once weekly ( three out of every four weeks) | 3 |
| Total | 4 |
Baseline characteristics
| Characteristic | Napabucasin Plus Paclitaxel | Paclitaxel Only | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 2 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 3 Participants | 4 Participants |
| Sex: Female, Male Female | 1 Participants | 3 Participants | 4 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 1 | 1 / 2 |
| other Total, other adverse events | 1 / 1 | 2 / 2 |
| serious Total, serious adverse events | 0 / 1 | 0 / 2 |
Outcome results
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.
Time frame: 36 months
Population: The study was terminated early by the sponsor after 4 patients were randomized (3 to the control arm and 1 to receive napabucasin). Due to the small sample size, no data summaries were performed and there is no analysis for statistical interference.
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.
Time frame: 36 months
Population: The study was terminated early by the sponsor after 4 patients were randomized (3 to the control arm and 1 to receive napabucasin). Due to the small sample size, no data summaries were performed and there is no analysis for statistical interference.
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.
Time frame: 36 months
Population: The study was terminated early by the sponsor after 4 patients were randomized (3 to the control arm and 1 to receive napabucasin). Due to the small sample size, no data summaries were performed and there is no analysis for statistical interference
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.
Time frame: 36 months
Population: The study was terminated early by the sponsor after 4 patients were randomized (3 to the control arm and 1 to receive napabucasin). Due to the small sample size, no data summaries were performed and there is no analysis for statistical interference.
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.
Time frame: 36 months
Population: The study was terminated early by the sponsor after 4 patients were randomized (3 to the control arm and 1 to receive napabucasin). Due to the small sample size, no data summaries were performed and there is no analysis for statistical interference.
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.
Time frame: 36 months
Population: The study was terminated early by the sponsor after 4 patients were randomized (3 to the control arm and 1 to receive napabucasin). Due to the small sample size, no data summaries were performed and there is no analysis for statistical interference
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.
Time frame: 36 months
Population: The study was terminated early by the sponsor after 4 patients were randomized (3 to the control arm and 1 to receive napabucasin). Due to the small sample size, no data summaries were performed and there is no analysis for statistical interference.
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.
Time frame: 36 months
Population: The study was terminated early by the sponsor after 4 patients were randomized (3 to the control arm and 1 to receive napabucasin). Due to the small sample size, no data summaries were performed and there is no analysis for statistical interference.