<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02231723</url>
  </required_header>
  <id_info>
    <org_study_id>BBI608-118</org_study_id>
    <secondary_id>BBI608-201PANC</secondary_id>
    <nct_id>NCT02231723</nct_id>
  </id_info>
  <brief_title>A Study of BBI608 in Combination With Standard Chemotherapies in Adult Patients With Pancreatic Cancer</brief_title>
  <official_title>A Phase Ib Clinical Study of BBI608 in Combination With Standard Chemotherapies in Adult Patients With Metastatic Pancreatic Adenocarcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sumitomo Pharma Oncology, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sumitomo Pharma Oncology, Inc.</source>
  <brief_summary>
    <textblock>
      This is an open label, multi-center, multi-arm, dose-escalation study of BBI608 administered&#xD;
      in combination with Gemcitabine and nab-Paclitaxel, mFOLFIRINOX, FOLFIRI, or MM-398 with 5-FU&#xD;
      and leucovorin.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is an open label, multi-center, multi-arm, dose-escalation study of BBI608 administered&#xD;
      in combination with either Gemcitabine and nab-Paclitaxel, mFOLFIRINOX, FOLFIRI, or MM-398&#xD;
      with 5-FU and leucovorin. A study cycle will consist of daily and continuous oral&#xD;
      administration of BBI608 for four weeks (28 days) in combination with Gemcitabine and&#xD;
      nab-Paclitaxel, mFOLFIRINOX, FOLFIRI, or MM-398 with 5-FU and leucovorin. Combination&#xD;
      treatment will continue in 28 day cycles until disease progression, unacceptable toxicity or&#xD;
      another discontinuation criterion is met. BBI608 may be continued post-progression if the&#xD;
      patient is obtaining potential clinical benefit, in the opinion of the investigator. If&#xD;
      administration of Gemcitabine and/or nab-Paclitaxel, mFOLFIRINOX, FOLFIRI, or MM-398 with&#xD;
      5-FU and leucovorin is discontinued due to chemotherapy backbone-related toxicities, the&#xD;
      administration of BBI608 can be continued.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2014</start_date>
  <completion_date type="Actual">June 2020</completion_date>
  <primary_completion_date type="Actual">June 2020</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety by reporting the adverse events and serious adverse events</measure>
    <time_frame>6 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Determination of the Recommended Phase 2 Dose by assessing dose-limiting toxicities (DLTs)</measure>
    <time_frame>3 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Assess the preliminary anti-tumor activity of BBI608 when administered in combination with standard chemotherapies by performing tumor assessments every 8 weeks</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assess the preliminary anti-tumor activity of BBI608 when administered in combination with standard chemotherapies by performing serum CA 19-9 level measurement</measure>
    <time_frame>6 months</time_frame>
    <description>Assess the preliminary anti-tumor activity of BBI608 when administered in combination with standard chemotherapies in adult patients with metastatic pancreatic adenocarcinoma by performing serum carbohydrate antigen 19-9 (CA 19-9) level measurement every 4 weeks</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assess pharmacokinetic profile of BBI608 when administered in combination with standard chemotherapies</measure>
    <time_frame>On Day 1 and Day 15 of the first cycle prior to dosing and 1, 2, 3, 3.5, 4, 5, 5.5, 7, 8, 9, 10, 11 and 24 hours after first dose</time_frame>
    <description>Blood sampling to assess the pharmacokinetic profile (Area under the curve) of BBI608.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assess pharmacodynamic activity of BBI608 when administered in combination with standard chemotherapies</measure>
    <time_frame>During the first 28 days of treatment</time_frame>
    <description>Tumor Biopsy to provide information of the biomarkers by histopathology and Cancer Stem Cell assays.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">139</enrollment>
  <condition>Metastatic Pancreatic Adenocarcinoma</condition>
  <arm_group>
    <arm_group_label>A: BBI608 in combination with Gemcitabine and nab-Paclitaxel</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>B: BBI608 in combination with modified FOLFIRINOX</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>C: BBI608 in combination with FOLFIRI</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>D: BBI608 in combination with MM-398, 5-FU and leucovorin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BBI608</intervention_name>
    <description>Administered continuously twice daily with doses separated by 12 hours</description>
    <arm_group_label>A: BBI608 in combination with Gemcitabine and nab-Paclitaxel</arm_group_label>
    <arm_group_label>B: BBI608 in combination with modified FOLFIRINOX</arm_group_label>
    <arm_group_label>C: BBI608 in combination with FOLFIRI</arm_group_label>
    <arm_group_label>D: BBI608 in combination with MM-398, 5-FU and leucovorin</arm_group_label>
    <other_name>Napabucasin</other_name>
    <other_name>BB608</other_name>
    <other_name>BBI-608</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nab-paclitaxel</intervention_name>
    <description>Nab-paclitaxel 125 mg/m^2 I.V. infusion on Days 1, 8, and 15 of every 28-day cycle</description>
    <arm_group_label>A: BBI608 in combination with Gemcitabine and nab-Paclitaxel</arm_group_label>
    <other_name>Abraxane, nanoparticle albumin-bound paclitaxel, paclitaxel, ABI-007</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Gemcitabine</intervention_name>
    <description>Gemcitabine 1000 mg/m^2 I.V. infusion on Days 1, 8, and 15 of every 28-day cycle</description>
    <arm_group_label>A: BBI608 in combination with Gemcitabine and nab-Paclitaxel</arm_group_label>
    <other_name>Gemzar</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oxaliplatin</intervention_name>
    <description>Oxaliplatin 85 mg/m^2 I.V. infusion on Days 1 and 15 of every 28-day cycle</description>
    <arm_group_label>B: BBI608 in combination with modified FOLFIRINOX</arm_group_label>
    <other_name>Eloxatin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Leucovorin</intervention_name>
    <description>Arm C, D: Leucovorin 400 mg/m^2 I.V. infusion on Days 1 and 15 of every 28-day cycle</description>
    <arm_group_label>C: BBI608 in combination with FOLFIRI</arm_group_label>
    <arm_group_label>D: BBI608 in combination with MM-398, 5-FU and leucovorin</arm_group_label>
    <other_name>Folinic Acid</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Irinotecan</intervention_name>
    <description>Arm B: Irinotecan 165 mg/m^2 I.V. infusion on Days 1 and 15 of every 28-day cycle, Arm C: Irinotecan 165 mg/m^2 I.V. infusion on Days 1 and 15 of every 28-day cycle</description>
    <arm_group_label>B: BBI608 in combination with modified FOLFIRINOX</arm_group_label>
    <arm_group_label>C: BBI608 in combination with FOLFIRI</arm_group_label>
    <other_name>Camptosar</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fluorouracil</intervention_name>
    <description>Arm B, D: Fluorouracil 2400 mg/m^2 I.V. infusion on Days 1 and 15 of every 28-day cycle, Arm C: Fluorouracil 400 mg/m^2 I.V. bolus followed by 2400 mg/m^2 I.V. infusion on Days 1 and 15 of every 28-day cycle</description>
    <arm_group_label>B: BBI608 in combination with modified FOLFIRINOX</arm_group_label>
    <arm_group_label>C: BBI608 in combination with FOLFIRI</arm_group_label>
    <arm_group_label>D: BBI608 in combination with MM-398, 5-FU and leucovorin</arm_group_label>
    <other_name>5-FU</other_name>
    <other_name>Carac</other_name>
    <other_name>Efudex</other_name>
    <other_name>Fluoroplex</other_name>
    <other_name>Adrucil</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>MM-398</intervention_name>
    <description>MM-398 70 mg/m^2 I.V. infusion on Days 1 and 15 of every 28-day cycle</description>
    <arm_group_label>D: BBI608 in combination with MM-398, 5-FU and leucovorin</arm_group_label>
    <other_name>Onivyde</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Signed written informed consent must be obtained and documented according to&#xD;
             International Conference on Harmonisation (ICH) - Good Clinical Practice (GCP), the&#xD;
             local regulatory requirements, and permission to use private health information in&#xD;
             accordance with the Health Insurance Portability and Accountability Act (HIPAA) prior&#xD;
             to study-specific screening procedures.&#xD;
&#xD;
          2. Patients must have histologic or cytologic evidence of adenocarcinoma of the pancreas,&#xD;
             such as a core tissue biopsy or a surgical resection specimen.&#xD;
&#xD;
          3. Patients must have metastatic disease. Baseline imaging of chest, abdomen and pelvis&#xD;
             (CT or MRI) within 21 days prior to initiation of protocol therapy is required.&#xD;
&#xD;
               1. Patients must have measurable disease as defined by RECIST 1.1.&#xD;
&#xD;
               2. Patients with locally advanced unresectable pancreatic ductal adenocarcinoma are&#xD;
                  excluded.&#xD;
&#xD;
          4. Patients enrolling onto Arm A (Gemcitabine and nab-Paclitaxel) or Arm B (mFOLFIRINOX)&#xD;
             are allowed to have up to two prior lines of systemic therapy, with adjuvant therapy&#xD;
             counted as one line of therapy as long as disease recurrence occurred &gt; 6 months of&#xD;
             last dose of therapy. Prior systemic therapy in the metastatic setting is allowed for&#xD;
             as long as the therapy contained BBI608 in combination with either Gemcitabine and&#xD;
             nab-Paclitaxel or mFOLFIRINOX. Toxicities related to prior therapy must have&#xD;
             completely resolved (except for alopecia and anemia), or be deemed irreversible.&#xD;
&#xD;
               1. Patients who received Gemcitabine-based therapy in an adjuvant setting will be&#xD;
                  allowed to be enrolled on Arm A of the trial (Gemcitabine with nab-Paclitaxel) as&#xD;
                  long as their last Gemcitabine administration was at least 6 months prior to the&#xD;
                  first dose of BBI608.&#xD;
&#xD;
               2. Patients enrolling onto Arm A (Gemcitabine with nab-Paclitaxel) are allowed to&#xD;
                  have prior mFOLFIRINOX in combination with BBI608 in the metastatic setting.&#xD;
&#xD;
               3. Patients enrolling onto Arm B (mFOLFIRINOX) are allowed to have prior Gemcitabine&#xD;
                  with nab-Paclitaxel in combination with BBI608 in the metastatic setting.&#xD;
&#xD;
               4. Prior treatment with radiotherapy is allowed.&#xD;
&#xD;
          5. Patients enrolling onto Arm C (FOLFIRI) or Arm D (MM-398 with 5-FU and leucovorin)&#xD;
             must have failed one prior line of gemcitabine-based therapy with or without BBI608 in&#xD;
             the metastatic setting. No additional lines of therapy in the metastatic setting are&#xD;
             allowed. Prior adjuvant therapy with gemcitabine is allowed as long as disease&#xD;
             recurrence occurred &gt; 6 months of last dose of therapy. Toxicities related to prior&#xD;
             therapy must have completely resolved (except for alopecia and anemia), or be deemed&#xD;
             irreversible. Prior treatment with radiotherapy is allowed.&#xD;
&#xD;
          6. ≥ 18 years of age.&#xD;
&#xD;
          7. Patients must have an ECOG Performance Status ≤ 1.&#xD;
&#xD;
          8. Male or female patients of child-producing potential agree to use contraception or&#xD;
             avoidance of pregnancy measures during the study and for 30 days after the last BBI608&#xD;
             dose.&#xD;
&#xD;
          9. Females of childbearing potential have a negative serum pregnancy test (preceding 72&#xD;
             hours of first day of BBI608 treatment).&#xD;
&#xD;
         10. Patients with biliary or gastro-duodenal obstruction must have drainage or surgical&#xD;
             bypass prior to starting chemotherapy.&#xD;
&#xD;
         11. Significant or symptomatic amount of ascites should be drained prior to first dose of&#xD;
             BBI608.&#xD;
&#xD;
         12. Patients on Warfarin/Dabigatran/Rivaroxaban anticoagulation may be enrolled for as&#xD;
             long as they undergo weekly INR checks for the first 2 months of therapy.&#xD;
&#xD;
             a. Patients who switch to low molecular weight heparin may be enrolled and weekly INR&#xD;
             labs are not mandated for these patients.&#xD;
&#xD;
         13. Aspartate transaminase (AST) level ≤ 2.5 x upper limit of normal (ULN) and alanine&#xD;
             transaminase (ALT) ≤ 2.5 × upper limit of normal (ULN). For patients with liver&#xD;
             metastases, AST ≤ 5 ULN, and AST ≤ 5 ULN may be enrolled if agreed upon by the&#xD;
             investigator and medical monitor for the sponsor.&#xD;
&#xD;
         14. Patients must have a total bilirubin level ≤ 1.5 x ULN (≤ 2 x ULN if it is non-rising&#xD;
             for a period of 10 days prior to initiation of therapy).&#xD;
&#xD;
         15. Creatinine level &lt; 1.0 x ULN or creatinine clearance ≥ 60 mL/min/1.73 m^2 for patients&#xD;
             with creatinine levels above or below the institutional normal (as determined by&#xD;
             Cockcroft-Gault equation). For patients with a Body Mass Index (BMI) &gt; 30 kg/m^2, lean&#xD;
             body weight should be used to calculate the GFR.&#xD;
&#xD;
         16. Hemoglobin (Hgb) ≥ 9 g/dl&#xD;
&#xD;
         17. Absolute neutrophil count ≥ 1.5 x 10^9/L&#xD;
&#xD;
         18. Platelets ≥ 100 x 10^9/L&#xD;
&#xD;
         19. Acceptable coagulation studies as demonstrated by prothrombin time (PT) and partial&#xD;
             thromboplastin time (PTT) within normal limits (+/-15%).&#xD;
&#xD;
         20. Patient has no clinically significant abnormalities on urinalysis results.&#xD;
&#xD;
         21. Life expectancy estimated at ≥ 3 months.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Anti-cancer chemotherapy, radiotherapy, immunotherapy, or investigational agents&#xD;
             within 14 days of the first dose of BBI608, except for BBI608 for which a washout&#xD;
             period is not required.&#xD;
&#xD;
               1. Patients may begin BBI608 on a date determined by the investigator and medical&#xD;
                  monitor for the sponsor after a minimum of 14 days since last receiving&#xD;
                  anti-cancer treatment which did not include BBI608, provided that all&#xD;
                  treatment-related adverse events have resolved or have been deemed irreversible&#xD;
                  (except for alopecia).&#xD;
&#xD;
               2. Patients who previously received BBI608 for treatment of PDAC on the BBI608-118&#xD;
                  (BBI608-201PANC) study may continue with BBI608 in monotherapy between&#xD;
                  discontinuation of the first chemotherapy backbone and start of the second&#xD;
                  chemotherapy backbone. Patients may begin chemotherapy backbone on a date&#xD;
                  determined by the investigator and medical monitor for the sponsor after a&#xD;
                  minimum of 14 days and a maximum of 30 days since last receiving anti-cancer&#xD;
                  treatment which included BBI608, provided that all treatment-related adverse&#xD;
                  events have resolved or have been deemed irreversible (except for alopecia).&#xD;
&#xD;
          2. Patients with neuroendocrine neoplasms will be excluded.&#xD;
&#xD;
          3. Major surgery, other than diagnostic surgery (e.g., surgery done to obtain a biopsy&#xD;
             for diagnosis without removal of an organ), within 4 weeks prior to first dose.&#xD;
&#xD;
          4. Any brain metastases including leptomeningeal metastases, are excluded, even if&#xD;
             treated and stable.&#xD;
&#xD;
          5. History of posterior reversible encephalopathy syndrome.&#xD;
&#xD;
          6. Neurosensory neuropathy ≥ grade 2 at baseline.&#xD;
&#xD;
          7. Pregnant or breastfeeding.&#xD;
&#xD;
          8. Significant gastrointestinal disorder(s) that would, in the opinion of the Principal&#xD;
             Investigator, prevent absorption of an orally available agent (e.g., Crohn's disease,&#xD;
             ulcerative colitis, extensive gastric resection and small intestinal resection).&#xD;
&#xD;
          9. Unable or unwilling to swallow BBI608 capsules daily.&#xD;
&#xD;
         10. Uncontrolled chronic diarrhea ≥ grade 2 at baseline.&#xD;
&#xD;
         11. Uncontrolled intercurrent illness including, but not limited to uncontrolled active&#xD;
             infection (including bacterial, viral or fungal requiring systemic therapy),&#xD;
             clinically significant non-healing or healing wounds, symptomatic congestive heart&#xD;
             failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, significant&#xD;
             pulmonary disease (shortness of breath at rest or mild exertion), uncontrolled&#xD;
             infection or psychiatric illness/social situations that would limit compliance with&#xD;
             study requirements.&#xD;
&#xD;
         12. Interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung.&#xD;
&#xD;
         13. History of other active malignancies.&#xD;
&#xD;
         14. Enrollment on any additional investigational agent study. Enrollment on concurrent&#xD;
             observational study is allowed following consultation with the Sponsor.&#xD;
&#xD;
         15. Patients planning to take a vacation for 7 or more consecutive days during the course&#xD;
             of the study.&#xD;
&#xD;
         16. For patients enrolling onto Arm A (Gemcitabine with nab-Paclitaxel)&#xD;
&#xD;
             a. Known hypersensitivity to Gemcitabine or taxanes. i. Patients with history of&#xD;
             Gemcitabine toxicity in the adjuvant setting requiring more than 1 dose level&#xD;
             reduction are excluded.&#xD;
&#xD;
             b. Significant cardiac disease, including the following: unstable angina, New York&#xD;
             Heart Association class III-IV congestive heart failure, myocardial infarction within&#xD;
             six months prior to study enrollment.&#xD;
&#xD;
             c. History of hemolytic-uremic syndrome. d. History of posterior reversible&#xD;
             encephalopathy syndrome. e. Known infection with Human Immunodeficiency Virus (HIV),&#xD;
             and/or active infection with hepatitis B, or hepatitis C.&#xD;
&#xD;
             f. History of active Peripheral Artery Disease (treated peripheral artery disease that&#xD;
             is stable for at least 6 months is allowed).&#xD;
&#xD;
         17. For patients enrolling onto Arm B (mFOLFIRINOX) or Arm C (FOLFIRI)&#xD;
&#xD;
               1. Known hypersensitivity to 5-fluorouracil/leucovorin&#xD;
&#xD;
               2. Known dihydropyrimidine dehydrogenase (DPD) deficiency&#xD;
&#xD;
               3. Known hypersensitivity to oxaliplatin or other platinum containing compounds&#xD;
&#xD;
               4. Known hypersensitivity to irinotecan&#xD;
&#xD;
               5. Uncontrolled seizure disorder, active neurological disease, or known CNS disease.&#xD;
&#xD;
               6. Known Gilbert's syndrome&#xD;
&#xD;
               7. Significant cardiac disease, including the following: unstable angina, New York&#xD;
                  Heart Association class II-IV congestive heart failure, myocardial infarction&#xD;
                  within six months prior to study enrollment.&#xD;
&#xD;
         18. For patients enrolling onto Arm D (MM-398 with 5-FU and leucovorin)&#xD;
&#xD;
               1. Prior irinotecan treatment&#xD;
&#xD;
               2. Arterial thromboembolic events (myocardial infarction, unstable angina pectoris,&#xD;
                  stroke) &lt; 6 months prior to enrollment&#xD;
&#xD;
               3. Known hypersensitivity to any of the components of MM-398, other liposomal&#xD;
                  products, fluoropyrimidines or leucovorin&#xD;
&#xD;
               4. Known dihydropyrimidine dehydrogenase (DPD) deficiency&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Mayo Clinic Arizona</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85054</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Emory University Winship Cancer Institute</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Parkview Research Center</name>
      <address>
        <city>Fort Wayne</city>
        <state>Indiana</state>
        <zip>46845</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Indiana University Health Goshen Center for Cancer Care</name>
      <address>
        <city>Goshen</city>
        <state>Indiana</state>
        <zip>46526</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Indiana University Melvin and Bren Simon Cancer Center</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Comprehensive Cancer Centers of Nevada</name>
      <address>
        <city>Henderson</city>
        <state>Nevada</state>
        <zip>89014</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Ohio State University Comprehensive Cancer Center</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The University of Tennessee Medical Center</name>
      <address>
        <city>Knoxville</city>
        <state>Tennessee</state>
        <zip>37920</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology - Austin Midtown</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>78705</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology - Baylor Charles A. Sammons Cancer Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75246</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology - SAT&amp;BC</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78216</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Virginia Oncology Associates</name>
      <address>
        <city>Norfolk</city>
        <state>Virginia</state>
        <zip>23502</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>August 30, 2014</study_first_submitted>
  <study_first_submitted_qc>September 2, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 4, 2014</study_first_posted>
  <last_update_submitted>April 4, 2022</last_update_submitted>
  <last_update_submitted_qc>April 4, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 5, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Digestive System Neoplasms</keyword>
  <keyword>Endocrine Gland Neoplasms</keyword>
  <keyword>Pancreatic neoplasms</keyword>
  <keyword>Pancreatic cancer, adult</keyword>
  <keyword>Pancreatic cancer</keyword>
  <keyword>Pancreas cancer</keyword>
  <keyword>Pancreatic diseases</keyword>
  <keyword>Adenoma, Islet Cell</keyword>
  <keyword>Carcinoma, Islet Cell</keyword>
  <keyword>Carcinoma, Pancreatic Ductal</keyword>
  <keyword>Gemcitabine</keyword>
  <keyword>Gemzar</keyword>
  <keyword>Nab-paclitaxel</keyword>
  <keyword>Paclitaxel</keyword>
  <keyword>Abraxane</keyword>
  <keyword>Oxaliplatin</keyword>
  <keyword>Leucovorin</keyword>
  <keyword>Irinotecan</keyword>
  <keyword>Fluorouracil</keyword>
  <keyword>5-FU</keyword>
  <keyword>MM-398</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Adenocarcinoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leucovorin</mesh_term>
    <mesh_term>Paclitaxel</mesh_term>
    <mesh_term>Albumin-Bound Paclitaxel</mesh_term>
    <mesh_term>Gemcitabine</mesh_term>
    <mesh_term>Fluorouracil</mesh_term>
    <mesh_term>Oxaliplatin</mesh_term>
    <mesh_term>Irinotecan</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02231723
org study id: BBI608-118
secondary id: BBI608-201PANC
nct id: NCT02231723
lead sponsor: 
This is an open label, multi-center, multi-arm, dose-escalation study of BBI608 administered
      in combination with Gemcitabine and nab-Paclitaxel, mFOLFIRINOX, FOLFIRI, or MM-398 with 5-FU
      and leucovorin.
This is an open label, multi-center, multi-arm, dose-escalation study of BBI608 administered
      in combination with either Gemcitabine and nab-Paclitaxel, mFOLFIRINOX, FOLFIRI, or MM-398
      with 5-FU and leucovorin. A study cycle will consist of daily and continuous oral
      administration of BBI608 for four weeks (28 days) in combination with Gemcitabine and
      nab-Paclitaxel, mFOLFIRINOX, FOLFIRI, or MM-398 with 5-FU and leucovorin. Combination
      treatment will continue in 28 day cycles until disease progression, unacceptable toxicity or
      another discontinuation criterion is met. BBI608 may be continued post-progression if the
      patient is obtaining potential clinical benefit, in the opinion of the investigator. If
      administration of Gemcitabine and/or nab-Paclitaxel, mFOLFIRINOX, FOLFIRI, or MM-398 with
      5-FU and leucovorin is discontinued due to chemotherapy backbone-related toxicities, the
      administration of BBI608 can be continued.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Safety by reporting the adverse events and serious adverse events
time frame: 6 months
measure: Determination of the Recommended Phase 2 Dose by assessing dose-limiting toxicities (DLTs)
time frame: 3 months
measure: Assess the preliminary anti-tumor activity of BBI608 when administered in combination with standard chemotherapies by performing tumor assessments every 8 weeks
time frame: 6 months
measure: Assess the preliminary anti-tumor activity of BBI608 when administered in combination with standard chemotherapies by performing serum CA 19-9 level measurement
time frame: 6 months
description: Assess the preliminary anti-tumor activity of BBI608 when administered in combination with standard chemotherapies in adult patients with metastatic pancreatic adenocarcinoma by performing serum carbohydrate antigen 19-9 (CA 19-9) level measurement every 4 weeks
measure: Assess pharmacokinetic profile of BBI608 when administered in combination with standard chemotherapies
time frame: On Day 1 and Day 15 of the first cycle prior to dosing and 1, 2, 3, 3.5, 4, 5, 5.5, 7, 8, 9, 10, 11 and 24 hours after first dose
description: Blood sampling to assess the pharmacokinetic profile (Area under the curve) of BBI608.
measure: Assess pharmacodynamic activity of BBI608 when administered in combination with standard chemotherapies
time frame: During the first 28 days of treatment
description: Tumor Biopsy to provide information of the biomarkers by histopathology and Cancer Stem Cell assays.
arm group label: A: BBI608 in combination with Gemcitabine and nab-Paclitaxel
arm group type: Experimental
arm group label: B: BBI608 in combination with modified FOLFIRINOX
arm group type: Experimental
arm group label: C: BBI608 in combination with FOLFIRI
arm group type: Experimental
arm group label: D: BBI608 in combination with MM-398, 5-FU and leucovorin
arm group type: Experimental
intervention type: Drug
intervention name: BBI608
description: Administered continuously twice daily with doses separated by 12 hours
arm group label: A: BBI608 in combination with Gemcitabine and nab-Paclitaxel
arm group label: B: BBI608 in combination with modified FOLFIRINOX
arm group label: C: BBI608 in combination with FOLFIRI
arm group label: D: BBI608 in combination with MM-398, 5-FU and leucovorin
other name: Napabucasin
other name: BB608
other name: BBI-608
intervention type: Drug
intervention name: Nab-paclitaxel
description: Nab-paclitaxel 125 mg/m^2 I.V. infusion on Days 1, 8, and 15 of every 28-day cycle
arm group label: A: BBI608 in combination with Gemcitabine and nab-Paclitaxel
other name: Abraxane, nanoparticle albumin-bound paclitaxel, paclitaxel, ABI-007
intervention type: Drug
intervention name: Gemcitabine
description: Gemcitabine 1000 mg/m^2 I.V. infusion on Days 1, 8, and 15 of every 28-day cycle
arm group label: A: BBI608 in combination with Gemcitabine and nab-Paclitaxel
other name: Gemzar
intervention type: Drug
intervention name: Oxaliplatin
description: Oxaliplatin 85 mg/m^2 I.V. infusion on Days 1 and 15 of every 28-day cycle
arm group label: B: BBI608 in combination with modified FOLFIRINOX
other name: Eloxatin
intervention type: Drug
intervention name: Leucovorin
description: Arm C, D: Leucovorin 400 mg/m^2 I.V. infusion on Days 1 and 15 of every 28-day cycle
arm group label: C: BBI608 in combination with FOLFIRI
arm group label: D: BBI608 in combination with MM-398, 5-FU and leucovorin
other name: Folinic Acid
intervention type: Drug
intervention name: Irinotecan
description: Arm B: Irinotecan 165 mg/m^2 I.V. infusion on Days 1 and 15 of every 28-day cycle, Arm C: Irinotecan 165 mg/m^2 I.V. infusion on Days 1 and 15 of every 28-day cycle
arm group label: B: BBI608 in combination with modified FOLFIRINOX
arm group label: C: BBI608 in combination with FOLFIRI
other name: Camptosar
intervention type: Drug
intervention name: Fluorouracil
description: Arm B, D: Fluorouracil 2400 mg/m^2 I.V. infusion on Days 1 and 15 of every 28-day cycle, Arm C: Fluorouracil 400 mg/m^2 I.V. bolus followed by 2400 mg/m^2 I.V. infusion on Days 1 and 15 of every 28-day cycle
arm group label: B: BBI608 in combination with modified FOLFIRINOX
arm group label: C: BBI608 in combination with FOLFIRI
arm group label: D: BBI608 in combination with MM-398, 5-FU and leucovorin
other name: 5-FU
other name: Carac
other name: Efudex
other name: Fluoroplex
other name: Adrucil
intervention type: Drug
intervention name: MM-398
description: MM-398 70 mg/m^2 I.V. infusion on Days 1 and 15 of every 28-day cycle
arm group label: D: BBI608 in combination with MM-398, 5-FU and leucovorin
other name: Onivyde
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
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country: United States
responsible party type: Sponsor
mesh term: Adenocarcinoma
mesh term: Leucovorin
mesh term: Paclitaxel
mesh term: Albumin-Bound Paclitaxel
mesh term: Gemcitabine
mesh term: Fluorouracil
mesh term: Oxaliplatin
mesh term: Irinotecan