We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study of Napabucasin Plus Nab-Paclitaxel With Gemcitabine in Adult Patients With Metastatic Pancreatic Adenocarcinoma (CanStem111P)

This study is currently recruiting participants.
Verified October 2017 by Boston Biomedical, Inc
Sponsor:
ClinicalTrials.gov Identifier:
NCT02993731
First Posted: December 15, 2016
Last Update Posted: October 16, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Boston Biomedical, Inc
  Purpose
This is a randomized, open-label, multi-center, phase 3 study of napabucasin plus weekly nab-paclitaxel with gemcitabine versus weekly nab-paclitaxel with gemcitabine for adult patients with Metastatic Pancreatic Ductal Adenocarcinoma.

Condition Intervention Phase
Carcinoma, Pancreatic Ductal Drug: Napabucasin Drug: Nab-paclitaxel Drug: Gemcitabine Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase III Study of BBI-608 Plus Nab-Paclitaxel With Gemcitabine in Adult Patients With Metastatic Pancreatic Adenocarcinoma

Resource links provided by NLM:


Further study details as provided by Boston Biomedical, Inc:

Primary Outcome Measures:
  • Overall Survival [ Time Frame: 36 months ]
    To assess the effect of napabucasin plus weekly nab-paclitaxel with gemcitabine versus weekly nab-paclitaxel with gemcitabine on the Overall Survival of patients with metastatic pancreatic ductal adenocarcinoma.


Secondary Outcome Measures:
  • Overall Survival in biomarker positive patients [ Time Frame: 36 months ]
    To assess the effect of napabucasin plus weekly nab-paclitaxel with gemcitabine versus weekly nab-paclitaxel with gemcitabine on the Overall Survival of patients with metastatic pancreatic ductal adenocarcinoma in biomarker positive patients. This biomarker-positive sub-population is defined as those patients with nuclear β-catenin and phospho-STAT3 positivity based on immunohistochemical (IHC) staining of Formalin Fixed Paraffin Embedded (FFPE) tumor tissue.

  • Progression Free Survival [ Time Frame: 36 months ]
    To assess the effect of napabucasin plus weekly nab-paclitaxel with gemcitabine versus weekly nab-paclitaxel with gemcitabine on the Progression Free Survival (PFS) of patients with metastatic pancreatic ductal adenocarcinoma. 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 [ Time Frame: 36 months ]
    To assess the effect of napabucasin plus weekly nab-paclitaxel with gemcitabine versus weekly nab-paclitaxel with gemcitabine on the Progression Free Survival (PFS) of patients with metastatic pancreatic ductal adenocarcinoma 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 nuclear β-catenin and phospho-STAT3 positivity based on immunohistochemical (IHC) staining of Formalin Fixed Paraffin Embedded (FFPE) tumor tissue.

  • Overall Response Rate [ Time Frame: 36 months ]
    To assess the effect of napabucasin plus weekly nab-paclitaxel with gemcitabine versus weekly nab-paclitaxel with gemcitabine on the Overall Response Rate (ORR) of patients with metastatic pancreatic ductal adenocarcinoma. ORR is evaluated using RECIST 1.1.

  • Disease Control Rate [ Time Frame: 36 months ]
    To assess the effect of napabucasin plus weekly nab-paclitaxel with gemcitabine versus weekly nab-paclitaxel with gemcitabine on the Disease Control Rate (DCR) of patients with metastatic pancreatic ductal adenocarcinoma. 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.

  • Overall Response Rate in biomarker positive patients [ Time Frame: 36 months ]
    To assess the effect of napabucasin plus weekly nab-paclitaxel with gemcitabine versus weekly nab-paclitaxel with gemcitabine on the Overall Response Rate (ORR) of patients with metastatic pancreatic ductal adenocarcinoma in biomarker positive patients. ORR is evaluated using RECIST 1.1. This biomarker-positive sub-population is defined as those patients with nuclear β-catenin and phospho-STAT3 positivity based on immunohistochemical (IHC) staining of Formalin Fixed Paraffin Embedded (FFPE) tumor tissue.

  • Disease Control Rate in biomarker positive patients [ Time Frame: 36 months ]
    To assess the effect of napabucasin plus weekly nab-paclitaxel with gemcitabine versus weekly nab-paclitaxel with gemcitabine on the Disease Control Rate (DCR) of patients with metastatic pancreatic ductal adenocarcinoma. 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 nuclear β-catenin and phospho-STAT3 positivity based on immunohistochemical (IHC) staining of Formalin Fixed Paraffin Embedded (FFPE) tumor tissue.

  • Quality of Life (QoL) [ Time Frame: 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 metastatic pancreatic ductal adenocarcinoma with napabucasin plus weekly nab-paclitaxel with gemcitabine versus weekly nab-paclitaxel with gemcitabine.

  • Number of Patients with Adverse Events [ Time Frame: 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.


Estimated Enrollment: 1132
Study Start Date: December 2016
Estimated Primary Completion Date: December 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1: Napabucasin plus Nab-paclitaxel with Gemcitabine
Patients randomized to this arm will receive napabucasin administered orally, twice daily in combination with weekly nab-paclitaxel and gemcitabine administered intravenously, once weekly, on 3 of every 4 weeks.
Drug: Napabucasin
Napabucasin will be administered orally, twice daily, with doses separated by approximately 12 hours.
Other Names:
  • BBI-608
  • BBI608
  • BB608
Drug: Nab-paclitaxel
Nab-paclitaxel 125 mg/m^2 immediately followed by gemcitabine 1000 mg/m^2 will be administered on Days 1, 8 and 15 of every 28-day cycle via intravenous infusion.
Other Name: Abraxane
Drug: Gemcitabine
Nab-paclitaxel 125 mg/m^2 immediately followed by gemcitabine 1000 mg/m^2 will be administered on Days 1, 8 and 15 of every 28-day cycle via intravenous infusion.
Other Name: Gemzar
Active Comparator: Arm 2: Nab-paclitaxel with Gemcitabine
Patients randomized to this arm will receive weekly nab-paclitaxel and gemcitabine administered intravenously, once weekly, on 3 of every 4 weeks.
Drug: Nab-paclitaxel
Nab-paclitaxel 125 mg/m^2 immediately followed by gemcitabine 1000 mg/m^2 will be administered on Days 1, 8 and 15 of every 28-day cycle via intravenous infusion.
Other Name: Abraxane
Drug: Gemcitabine
Nab-paclitaxel 125 mg/m^2 immediately followed by gemcitabine 1000 mg/m^2 will be administered on Days 1, 8 and 15 of every 28-day cycle via intravenous infusion.
Other Name: Gemzar

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Written, signed consent for trial participation must be obtained from the patient appropriately in accordance with applicable International Conference on Harmonization (ICH) guidelines and local and regulatory requirements prior to the performance of any study specific procedure.
  2. Must have histologically or cytologically confirmed advanced pancreatic ductal adenocarcinoma (PDAC) that is metastatic. The definitive diagnosis of metastatic PDAC will be made by integrating the histopathological data within the context of the clinical and radiographic data. Patients with islet cell neoplasms are excluded.
  3. Must not have previously received chemotherapy or any investigational agent for the treatment of metastatic PDAC. A fluoropyrimidine or gemcitabine administered as a radiation sensitizer in the adjuvant setting is allowed for as long as last dose was administered > 6 months prior to randomization and no lingering toxicities are present.
  4. Nab-paclitaxel with gemcitabine therapy is appropriate for the patient and recommended by the Investigator.
  5. Patient has one or more metastatic tumors evaluable by CT scan with contrast (or MRI, if patient is allergic to CT contrast media) per RECIST 1.1. Imaging investigations including CT/MRI of chest/abdomen/pelvis or other scans as necessary to document all sites of disease must be performed within 14 days prior to randomization. Qualifying scans performed as part of standard of care prior to patient signature of the study informed consent will be acceptable as baseline scanning as long as scanning is performed < 14 days prior to randomization.
  6. Must have Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1, assessed within 14 days prior to randomization. Two observers qualified to perform assessment of the performance status will be required to perform this assessment. If discrepant, the one with the most deteriorated performance status will be considered true.
  7. Must have life-expectancy of > 12 weeks.
  8. Must be ≥ 18 years of age. Due to increased risk of sepsis in patients >80 years old, candidate patients in this age group should be thoroughly evaluated prior to study randomization to ensure they are fit to receive chemotherapy. In addition to all of the inclusion/exclusion criteria listed, clinical judgment should be used regarding patients' susceptibility to infection (including but not limited to presence of ascites or diabetes mellitus increasing risk of infection). Furthermore, the expected stability of their performance status while receiving repeat weekly chemotherapy cycles should be given special attention. Patients in this age group should not be randomized on the study should there be any hesitation on any of these considerations.
  9. For male or female patients of child producing potential: Must agree to use contraception or take measures to avoid pregnancy during the study and for 180 days after the final dose of nab-paclitaxel and gemcitabine or for 30 days for female patients and for 90 days for male patients, after the final napabucasin dose if nab-paclitaxel and gemcitabine were not administered.
  10. Women of child bearing potential (WOCBP) must have a negative serum or urine pregnancy test within 5 days prior to randomization.
  11. Patient has adequate biological parameters as demonstrated by the following blood counts at baseline (obtained < 14 days prior to randomization; laboratory testing performed as part of standard of care prior to patient signature of informed consent for the study will be acceptable as baseline laboratory work as long as testing is performed < 14 days prior to randomization):

    1. Absolute neutrophil count (ANC) > 1.5 x 10^9/L
    2. Platelet count > 100,000/mm^3 (100 x 10^9/L). Must not have required transfusion of platelets within 1 week of baseline platelet count assessment.
    3. Hemoglobin (HgB) > 9 g/dL. Must not have required transfusion of red blood cells within 1 week of baseline Hgb assessment.
  12. Patient has the following blood chemistry levels at baseline (obtained < 14 days prior to randomization; laboratory testing performed as part of standard of care prior to patient signature of informed consent for the study will be acceptable as baseline laboratory work as long as testing is performed < 14 days prior to randomization):

    1. AST (SGOT) and ALT (SGPT) ≤ 2.5 × institutional upper limit of normal (ULN) [≤ 5 × ULN in presence of liver metastases]
    2. Total bilirubin ≤ 1.5 x institutional ULN. If total bilirubin is > ULN, it must be non-rising for at least 7 days.
    3. Serum creatinine within normal limits or calculated clearance > 60 mL/min/1.73 m^2 for patients with serum creatinine levels above or below the institutional normal value. If using creatinine clearance, actual body weight should be used for calculating creatinine clearance (eg. Using the Cockcroft-Gault formula). For patients with a Body Mass Index (BMI) > 30 kg/m^2, lean body weight should be used instead.
  13. Patient not on anticoagulation has acceptable coagulation studies (obtained < 14 days prior to randomization; laboratory testing performed as part of standard of care prior to patient signature of informed consent for the study will be acceptable as baseline laboratory work as long as testing is performed < 14 days prior to randomization) as demonstrated by prothrombin time (PT) and partial thromboplastin time (PTT) within normal limits (+15%).

    Patients on anticoagulation must have coagulation values within the therapeutic range appropriate for the anti-coagulation indication.

  14. Patient has no clinically significant abnormalities on urinalysis results (obtained < 14 days prior to randomization; laboratory testing performed as part of standard of care prior to patient signature of informed consent for the study will be acceptable as baseline laboratory work as long as testing is performed < 14 days prior to randomization).
  15. Patient must have adequate nutritional status with Body Mass Index (BMI) > 18 kg/m^2 and body weight of > 40 kg with serum albumin > 3 g/dL.
  16. Baseline laboratory evaluations must be done within 14 days prior to randomization and some must be repeated < 72 hours prior to randomization.
  17. Patients requiring biliary stent placement must have biliary stent placed > 7 days prior to screening.
  18. Pain symptoms should be stable (of tolerable Grade 2 or less).
  19. Only patients with available archival tumor tissue must consent to provision of, and Investigator(s) must confirm access to and agree to submit a representative formalin fixed paraffin block of tumor tissue in order that the specific correlative marker assays (Correlative Studies) of this protocol may be conducted. Submission of the tissue does not have to occur prior to randomization. Where local center regulations prohibit submission of blocks of tumor tissue, two 2 mm cores of tumor from the block and 5-20 unstained slides of whole sections of representative tumor tissue are preferred. Where it is not possible to obtain two 2 mm cores of tumor from the block, 5-20 unstained slides of representative tumor tissue are also acceptable. Where no previously resected or biopsied tumor tissue exists or is available, on the approval of the Sponsor/designated CRO, the patient may still be considered eligible for the study.
  20. Patient must consent to provision of a sample of blood in order that the specific correlative marker assays (Correlative Studies) may be conducted.
  21. Patients must be accessible for treatment and follow up. Patients registered on this trial must receive protocol treatment and be followed at the participating center. This implies there must be reasonable geographical limits placed on patients being considered for this trial. Investigators must ensure that the patients randomized on this trial will be available for complete documentation of the treatment, response assessment, adverse events, and follow-up.
  22. Protocol treatment is to begin within 2 calendar days of patient randomization for patients randomized to Arm 1. Patients randomized to Arm 2 must begin protocol treatment within 7 calendar days of randomization.
  23. The patient is not receiving therapy in a concurrent clinical study and the patient agrees not to participate in other interventional clinical studies during their participation in this trial while on study treatment. Patients participating in surveys or observational studies are eligible to participate in this study.

Exclusion Criteria:

  1. Patients with no evidence of metastatic disease as well as patients with a local recurrence following surgical resection of primary lesion.
  2. Patient has experienced a decline in ECOG performance status between Baseline visit and within 72 hours prior to randomization.
  3. Patient has a > 20% decrease in serum albumin level between Baseline visit and within 72 hours prior to randomization.
  4. Patient has a > 10% decrease in weight between Baseline visit and within 72 hours prior to randomization.
  5. Any prior anti-cancer chemotherapy, biologic or investigational therapy for PDAC.

    1. Patients receiving immunotherapy for non-cancer related treatment within < 4 weeks of first planned dose of study treatment will be excluded.
    2. A fluoropyrimidine or gemcitabine administered as a radiation sensitizer in the adjuvant setting is allowed for as long as last dose was administered > 6 months prior to randomization.
  6. Major surgery within 4 weeks prior to randomization.
  7. Any known brain or leptomeningeal metastases are excluded, even if treated.
  8. Patients with clinically significant ascites.
  9. Women who are pregnant or breastfeeding. Women should not breastfeed while taking study treatment and for 4 weeks after the last dose of napabucasin or while undergoing treatment with nab-paclitaxel and gemcitabine and for 180 days after the last dose of nab-paclitaxel and gemcitabine.
  10. Gastrointestinal disorder(s) which, in the opinion of the Principal Investigator, would significantly impede the absorption of an oral agent (e.g. active Crohn's disease, ulcerative colitis, extensive gastric and small intestine resection).
  11. Unable or unwilling to swallow napabucasin capsules daily.
  12. Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, clinically significant non-healing or healing wounds, symptomatic congestive heart failure, unstable angina pectoris, clinically significant cardiac arrhythmia, significant pulmonary disease (shortness of breath at rest or mild exertion), uncontrolled infection or psychiatric illness/social situations that would limit compliance with study requirements.

    1. History of cardiac disease: congestive heart failure (CHF) > New York Heart Association (NYHA) Class II; active coronary artery disease, myocardial infarction or coronary stenting within 6 months prior to randomization; unevaluated new onset angina within 3 months or unstable angina (angina symptoms at rest) or cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted).
    2. Current uncontrolled hypertension (systolic blood pressure [BP] > 150 mmHg or diastolic pressure > 90 mmHg despite optimal medical management) as well as prior history of hypertensive crisis or hypertensive encephalopathy.
    3. Significant vascular disease (e.g., aortic aneurysm, aortic dissection, symptomatic peripheral vascular disease including claudication, Leo Buerger's disease). Treated peripheral vascular disease that is stable for at least 6 months is allowed.
    4. Evidence of bleeding diathesis or clinically significant coagulopathy.
    5. Major surgical procedure (including open biopsy, significant traumatic injury, etc.) within 28 days, or anticipation of the need for major surgical procedure during the course of the study as well as minor surgical procedure (excluding placement of a vascular access device or bone marrow biopsy) within 7 days prior to randomization.
    6. Patients with clinically significant abnormalities on urinalysis at < 14 days prior to randomization.
    7. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to randomization.
    8. Ongoing serious, non-healing wound, ulcer, or bone fracture.
    9. Known infection with Human Immunodeficiency Virus (HIV), and/or active infection with hepatitis B, or hepatitis C.
    10. History of interstitial lung disease, history of slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis or multiple allergies.
    11. History of hemolytic-uremic syndrome.
    12. History of connective tissue disorders (eg, lupus, scleroderma, arteritis nodosa).
    13. Serious medical risk factors involving any of the major organ systems, or serious psychiatric disorders that could compromise the patient's safety or the study data integrity.
  13. Known hypersensitivity to gemcitabine, taxanes or any of their excipients, or the patient exhibits any of the events outlined in the Contraindications or Special Warnings and Precautions sections of the product or comparator Summary of Product Characteristics or Prescribing Information.
  14. Neurosensory neuropathy > grade 2 at baseline.
  15. Uncontrolled chronic diarrhea > grade 2 at baseline.
  16. Patients being treated with Warfarin.
  17. Patients with active, uncontrolled bacterial, viral or fungal infection(s) requiring systemic therapy
  18. Patients with a history of other malignancies except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumors curatively treated by surgery alone or surgery plus radiotherapy with no evidence of disease continuously for > 5 years.
  19. Any active disease condition which would render the protocol treatment dangerous or impair the ability of the patient to receive protocol therapy.
  20. Any condition (e.g. psychological, geographical, etc.) that does not permit compliance with the protocol, including patients with history of poor compliance or history of drug/alcohol abuse, or excessive alcohol beverage consumption that would interfere with the ability to comply with the study protocol. Patients planning to take a vacation for 14 or more consecutive days during the course of the study are ineligible.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02993731


Contacts
Contact: Boston Biomedical 617-674-6800

  Show 77 Study Locations
Sponsors and Collaborators
Boston Biomedical, Inc
Investigators
OverallOfficial: Boston Biomedical
  More Information

Responsible Party: Boston Biomedical, Inc
ClinicalTrials.gov Identifier: NCT02993731     History of Changes
Other Study ID Numbers: CanStem111P
First Submitted: December 13, 2016
First Posted: December 15, 2016
Last Update Posted: October 16, 2017
Last Verified: October 2017

Keywords provided by Boston Biomedical, Inc:
Neoplasms
Neoplasms by Site
Digestive System Neoplasms
Endocrine Gland Neoplasms
Pancreatic Neoplasms
Adenocarcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Albumin-Bound Paclitaxel
Gemcitabine

Additional relevant MeSH terms:
Adenocarcinoma
Carcinoma, Pancreatic Ductal
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Carcinoma, Ductal
Neoplasms, Ductal, Lobular, and Medullary
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Paclitaxel
Gemcitabine
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents