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A Study of BBI608 in Adult Patients With Advanced Colorectal Cancer

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ClinicalTrials.gov Identifier: NCT01776307
Recruitment Status : Completed
First Posted : January 28, 2013
Results First Posted : June 18, 2021
Last Update Posted : June 18, 2021
Sponsor:
Information provided by (Responsible Party):
Sumitomo Dainippon Pharma Oncology, Inc

Tracking Information
First Submitted Date  ICMJE January 21, 2013
First Posted Date  ICMJE January 28, 2013
Results First Submitted Date  ICMJE May 20, 2021
Results First Posted Date  ICMJE June 18, 2021
Last Update Posted Date June 18, 2021
Study Start Date  ICMJE March 2012
Actual Primary Completion Date June 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 16, 2021)
Disease Control Rate [ Time Frame: From the date of first treatment, every 8 weeks, until the date of first documented objective disease progression, up to 24 months ]
Assessment of Disease Control Rate, defined as the proportion of patients with a documented complete response, partial response and stable disease based on RECIST 1.1, in patients with advanced colorectal cancer given napabucasin in combination with cetuximab, panitumumab or capecitabine
Original Primary Outcome Measures  ICMJE
 (submitted: January 23, 2013)
Disease Control Rate [ Time Frame: 8 weeks ]
Assessment of Disease Control Rate, defined as the proportion of patients with a documented complete response, partial response and stable disease based on RECIST, in patients with advanced colorectal cancer given BBI608 in combination with cetuximab, panitumumab or capecitabine
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 16, 2021)
  • Progression Free Survival [ Time Frame: The time from the date of first treatment to the date of first documentation of disease progression or death due to any cause, up to 24 months ]
    The effect of napabucasin given in combination with cetuximab, panitumumab or capecitabine on Progression Free Survival (PFS) of patients with advanced colorectal cancer.
  • Overall Survival [ Time Frame: 4 weeks after the patient has been off study treatment, every 3 months thereafter until death, up to 60 months. ]
    The effect of napabucasin given in combination with cetuximab, panitumumab or capecitabine on the Overall Survival of patients with advanced colorectal cancer
  • Determination of the Maximum Observed Concentration (Cmax) of Napabucasin When Administered 480mg, Twice Daily, on Day 5 of the First Study Cycle [ Time Frame: Blood samples drawn on day 5 during the first study cycle ]
    To determine the maximum concentration of napabucasin when given at 480mg, twice daily, in combination with cetuximab, panitumumab, or capecitabine in patients with advanced colorectal cancer.
  • Determination of the Maximum Observed Concentration (Cmax) of Napabucasin When Administered 480mg, Twice Daily, on Day 21 of the First Study Cycle [ Time Frame: Blood samples drawn on day 21 during the first study cycle ]
    To determine the maximum concentration of napabucasin when given at 480mg, twice daily, in combination with cetuximab, panitumumab, or capecitabine in patients with advanced colorectal cancer.
  • Determination of the Maximum Observed Concentration (Cmax) of Napabucasin When Administered 240mg, Twice Daily, on Day 21 of the First Study Cycle [ Time Frame: Blood samples drawn on day 21 during the first study cycle ]
    To determine the maximum concentration of napabucasin when given at 240mg, twice daily, in combination with cetuximab, panitumumab, or capecitabine in patients with advanced colorectal cancer.
  • Determination of the Maximum Observed Concentration (Cmax) of Napabucasin When Administered 500mg, Twice Daily, on Day 5 of the First Study Cycle [ Time Frame: Blood samples drawn on day 5 during the first study cycle ]
    To determine the maximum concentration of napabucasin when given at 500mg, twice daily, in combination with cetuximab, panitumumab, or capecitabine in patients with advanced colorectal cancer.
  • Determination of the Maximum Observed Concentration (Cmax) of Napabucasin When Administered 500mg, Twice Daily, on Day 21 of the First Study Cycle [ Time Frame: Blood samples drawn on day 21 during the first study cycle ]
    To determine the maximum concentration of napabucasin when given at 500mg, twice daily, in combination with cetuximab, panitumumab, or capecitabine in patients with advanced colorectal cancer.
  • Area Under the Plasma Concentration vs. Time Curve (AUClast) of Napabucasin When Administered 480mg, Twice Daily, on Day 5 of the First Study Cycle [ Time Frame: Blood samples drawn on day 5 during the first study cycle ]
    To determine the area under the plasma concentration vs. time curve of napabucasin when given at 480mg, twice daily, in combination with cetuximab, panitumumab, or capecitabine in patients with advanced colorectal cancer.
  • Area Under the Plasma Concentration vs. Time Curve (AUClast) of Napabucasin When Administered 480mg, Twice Daily, on Day 21 of the First Study Cycle [ Time Frame: Blood samples drawn on day 21 during the first study cycle ]
    To determine the area under the plasma concentration vs. time curve of napabucasin when given at 480mg, twice daily, in combination with cetuximab, panitumumab, or capecitabine in patients with advanced colorectal cancer.
  • Area Under the Plasma Concentration vs. Time Curve (AUClast) of Napabucasin When Administered 240mg, Twice Daily, on Day 21 of the First Study Cycle [ Time Frame: Blood samples drawn on day 21 during the first study cycle ]
    To determine the area under the plasma concentration vs. time curve of napabucasin when given at 240mg, twice daily, in combination with cetuximab, panitumumab, or capecitabine in patients with advanced colorectal cancer.
  • Area Under the Plasma Concentration vs. Time Curve (AUClast) of Napabucasin When Administered 500mg, Twice Daily, on Day 5 of the First Study Cycle [ Time Frame: Blood samples drawn on day 5 during the first study cycle ]
    To determine the area under the plasma concentration vs. time curve of napabucasin when given at 500mg, twice daily, in combination with cetuximab, panitumumab, or capecitabine in patients with advanced colorectal cancer.
  • Area Under the Plasma Concentration vs. Time Curve (AUClast) of Napabucasin When Administered 500mg, Twice Daily, on Day 21 of the First Study Cycle [ Time Frame: Blood samples drawn on day 21 during the first study cycle ]
    To determine the area under the plasma concentration vs. time curve of napabucasin when given at 500mg, twice daily, in combination with cetuximab, panitumumab, or capecitabine in patients with advanced colorectal cancer.
  • Pharmacodynamics [ Time Frame: During the first 28 days of the study cycle ]
    To determine the response (increase or decrease) of biomarkers from biopsied tumors following the administration of napabucasin
  • Number of Patients With Adverse Events and Serious Adverse Events [ Time Frame: The time from the date of first treatment, while the patient is taking napabucasin, and for 30 days after stopping therapy, an average of 4 months. ]
    Assessment of safety of napabucasin given in combination with cetuximab, panitumumab or capecitabine to patients with advanced colorectal cancer by reporting of adverse events and serious adverse events
Original Secondary Outcome Measures  ICMJE
 (submitted: January 23, 2013)
  • Overall Survival [ Time Frame: From date of randomization until the date of death, assessed up to 100 months ]
    Assessment of Overall Survival in patients with advanced colorectal cancer given BBI608 in combination with cetuximab, panitumumab or capecitabine
  • Progression Free Survival [ Time Frame: From date of randomization until the date of first documented progression or death, whichever comes first, assessed up to 100 months ]
    Assessment of Progression Free Survival in patients with advanced colorectal cancer given BBI608 in combination with cetuximab, panitumumab or capecitabine by performing tumor assessments every 8 weeks.
  • Safety [ Time Frame: Adverse events will be assessed at baseline, while the participant is taking BBI608, and for 30 days after stopping therapy. The average length of this duration is expected to be approximately 4 months. ]
    Assessment of safety of BBI608 given in combination with cetuximab, panitumumab or capecitabine to patients with advanced colorectal cancer by reporting of adverse events and serious adverse events
  • Pharmacokinetics [ Time Frame: On Day 5 and Day 26 in the cetuximab combination arm; on Day 8 and 22 in the panitumumab combination arm; and on Day 8 and 21 in the capecitabine combination arm ]
    Observe the area under the plasma concentration versus time curve of BBI608 in combination with cetuximab, BBI608 in combination with panitumumab, and BBI608 in combination with capecitabine
  • Pharmacodynamics [ Time Frame: At baseline and at 4 hours after administration of BBI608 morning dose on Day 8 ]
    Pharmacodynamic assessments to analyze biomarkers in tumor tissues will be performed in patients when tumor biopsy with a minimally invasive procedure is deemed possible by Investigator.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of BBI608 in Adult Patients With Advanced Colorectal Cancer
Official Title  ICMJE A Phase II Clinical Study of BBI608 in Adult Patients With Advanced Colorectal Cancer
Brief Summary This is an open label, multi-center, Phase 2 study of BBI608 in combination with cetuximab, panitumumab or capecitabine in patients with advanced colorectal cancer.
Detailed Description This is an open label, multi-center, Phase 2 study of BBI608 administered in combination with either cetuximab, or panitumumab, or capecitabine. A cycle will consist of daily and continuous oral administration of BBI608 for four weeks in combination with either cetuximab, or panitumumab, or capecitabine.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Colorectal Cancer
Intervention  ICMJE
  • Drug: BBI608
    BBI608 is administered at 500 mg po bid continuously.
    Other Names:
    • Napabucasin
    • BB608
    • BBI-608
  • Drug: Panitumumab
    Panitumumab will be administered IV on day 8 and 22 of each 28 day cycle at 6 mg/kg over 60 minutes.
    Other Name: Vectibix
  • Drug: Capecitabine
    Capecitabine will be administered orally at 1000 mg/m2 bid daily on days 8-21 every three weeks.
    Other Name: Xeloda
  • Drug: Cetuximab
    Cetuximab will be administered IV on day 5 at 400 mg/m2 intravenous infusion over 120 minutes as the initial dose, then weekly at 250mg/m2 over 60-minutes at subsequent cycles.
    Other Name: Erbitux
Study Arms  ICMJE
  • Experimental: BBI608 in combination with cetuximab
    Interventions:
    • Drug: BBI608
    • Drug: Cetuximab
  • Experimental: BBI608 in combination with panitumumab
    Interventions:
    • Drug: BBI608
    • Drug: Panitumumab
  • Experimental: BBI608 in combination with capecitabine
    Interventions:
    • Drug: BBI608
    • Drug: Capecitabine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 16, 2021)
200
Original Estimated Enrollment  ICMJE
 (submitted: January 23, 2013)
66
Actual Study Completion Date  ICMJE April 2020
Actual Primary Completion Date June 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Signed written informed consent must be obtained and documented according to International Conference on Harmonization (ICH), Good Clinical Practice(GCP), the local regulatory requirements, and permission to use private health information in accordance with the Health Insurance Portability and Accountability Act (HIPPA) prior to study-specific screening procedures.
  • A histologically or cytologically confirmed colorectal cancer that is metastatic, unresectable, or recurrent.
  • Patients must have received at least 2 regimens containing 5-Fluorouracil,oxaliplatin, or irinotecan.
  • Patients to be enrolled in the Cetuximab or Panitumumab combination arms must have colorectal cancer which is K-Ras wild-type.
  • ≥ 18 years of age.
  • Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST 1.1).
  • Karnofsky performance Status ≥ 70%
  • Male or female patients of child-producing potential must agree to use contraception or avoidance of pregnancy measures during the study and for 30 days after the last BBI608 dose.
  • Females of childbearing potential must have a negative serum pregnancy test.
  • Aspartate transaminase (AST) and alanine transaminase (ALT) ≤1.5 × upper limit of normal(ULN), or ≤ 2.5 × ULN with metastatic liver disease.
  • Hemoglobin (Hgb) ≥ 10 g/dl.
  • Total bilirubin ≤ 1.5 × ULN.
  • Creatinine ≤ 1.5 × ULN or creatinine clearance > 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal.
  • Absolute neutrophil count ≥ 1.5 x 10^9/L.
  • Platelets ≥ 100 x 10^9/L.
  • Life expectancy ≥ 3 months.

Exclusion Criteria:

  • Anti-cancer chemotherapy, radiotherapy, immunotherapy, or investigational agents within four weeks of first dose with the exception for a single dose radiation up to 8 Gray (equal to 800 RAD) with palliative intent for pain control up to 14 days before beginning the administration of BBI608.
  • Surgery within 4 weeks prior to first dose.
  • Any known symptomatic brain metastases requiring steroids. Patients with treated brain metastases must be stable for 4 weeks after completion of that treatment, with image documentation required. Patients must have no clinical symptoms from brain metastases and must be either off steroids or on a stable dose of steroids for at least 2 weeks prior to protocol enrollment. Patients with known leptomeningeal metastases are excluded, even if treated.
  • Pregnant or breastfeeding
  • Significant gastrointestinal disorder(s), in the opinion of the Principal Investigator, (e.g., Crohn's disease, ulcerative colitis, extensive gastric and small intestine resection)
  • Unable or unwilling to swallow BBI608 capsules daily.
  • Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, clinically significant non-healing or healing wounds, symptomatic congestive heart failure, unstable angina pectoris, 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01776307
Other Study ID Numbers  ICMJE BBI608-224
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Sumitomo Dainippon Pharma Oncology, Inc
Study Sponsor  ICMJE Sumitomo Dainippon Pharma Oncology, Inc
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: William J. Edenfield, MD Institute for Translational Oncology Research, Greenville Hospital System
PRS Account Sumitomo Dainippon Pharma Oncology, Inc
Verification Date June 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP