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Change of treatment landscape and evolving standard of care
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Napabucasin plus Weekly Paclitaxel | Experimental | 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. |
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| Weekly Paclitaxel | Active Comparator | Patients randomized to this arm will receive weekly paclitaxel alone administered intravenously, once weekly, on 3 of every 4 weeks. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Napabucasin | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Key Inclusion Criteria:
Key Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Beverly Hills | California | United States | ||||
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| ID | Title | Description |
|---|---|---|
| FG000 | Napabucasin Plus Paclitaxel | All participants were randomized to receive napabucasin (BBI-608) 240 mg administered orally, twice daily (480 mg total in a day) plus Paclitaxel 80 mg/m2 IV; once weekly ( three out of every four weeks) |
| FG001 | Paclitaxel Only |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jul 12, 2016 | Mar 22, 2021 |
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| Paclitaxel | Drug | 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. |
|
| 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. | 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. | 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. | 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. | 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. | 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. | 36 months |
| Santa Rosa |
| California |
| United States |
| Aventura | Florida | United States |
| Gettysburg | Pennsylvania | United States |
| Arlington | Texas | United States |
All participants were randomized to receive Paclitaxel 80 mg/m2 IV, once weekly ( three out of every four weeks) |
| Discontinued Due to Treatment Related AE |
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| Discontinued Due to Death |
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| Discontinued Due to Patient Withdrawal |
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| Discontinued Due to Withdrawal of ICF From Further FU |
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| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | 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) |
| BG001 | Paclitaxel Only | All participants randomized to receive Paclitaxel 80 mg/m2 IV, once weekly ( three out of every four weeks) |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | 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. | Posted | 36 months |
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| 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. | 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. | Posted | 36 months |
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| 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. | 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 | Posted | 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. | 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. | Posted | 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. | 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 | Posted | 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. | 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. | Posted | 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. | 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. | Posted | 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. | 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. | Posted | 36 months |
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The safety documentation and reporting begins with completion of the informed consent and extends until 30 days following the last dose of the protocol therapy, the total period is 36 months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Napabucasin+Paclitaxel | All participants part of the safety population ( those who received at least 1 dose of study drug napabucasin). | 1 | 1 | 0 | 1 | 1 | 1 |
| EG001 | Paclitaxel Only | All participants part of the safety population ( those who received at least 1 dose of paclitaxel). | 1 | 2 | 0 | 2 | 2 | 2 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | Systematic Assessment |
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| Costipation | Gastrointestinal disorders | Systematic Assessment |
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| Epistaxis | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Abdominal Infection | Infections and infestations | Systematic Assessment |
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| Dysgeusia | Nervous system disorders | Systematic Assessment |
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| Alopecia | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Dehydration | Metabolism and nutrition disorders | Systematic Assessment |
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| Asthenia | General disorders | Systematic Assessment |
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| Edema Lower Legs | General disorders | Systematic Assessment |
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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.
Before submission for publication or presentation, Institution and/or Investigator shall allow Sponsor not less than sixty ( 60) days to review any manuscript and not less than thirty ( 30) days to review any poster presentation, abstract or any other written or oral material which describes or discloses the study results. If Sponsor requests in writing, institution and/or Investigator shall withhold any publication or presentation for an additional sixty ( 60) days.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Matthew Hitron, MD | Sumitomo Dainippon Pharma Oncology | 617-674-6800 | mhitron@bostonbiomedical.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Aug 8, 2017 | Mar 22, 2021 | SAP_001.pdf |
| ID | Term |
|---|---|
| D002289 | Carcinoma, Non-Small-Cell Lung |
| D009369 | Neoplasms |
| D009371 | Neoplasms by Site |
| D008175 | Lung Neoplasms |
| D013899 | Thoracic Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
| D001984 | Bronchial Neoplasms |
| ID | Term |
|---|---|
| D002283 | Carcinoma, Bronchogenic |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D001982 | Bronchial Diseases |
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| ID | Term |
|---|---|
| C000621033 | napabucasin |
| D017239 | Paclitaxel |
| ID | Term |
|---|---|
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D004224 | Diterpenes |
| D013729 | Terpenes |
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| >=65 years |
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| Male |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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