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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

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.

Condition or disease Intervention/treatment Phase
Colorectal Cancer Drug: BBI608 Drug: Panitumumab Drug: Capecitabine Drug: Cetuximab Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 200 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Clinical Study of BBI608 in Adult Patients With Advanced Colorectal Cancer
Study Start Date : March 2012
Actual Primary Completion Date : June 2018
Actual Study Completion Date : April 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: BBI608 in combination with cetuximab Drug: BBI608
BBI608 is administered at 500 mg po bid continuously.
Other Names:
  • Napabucasin
  • BB608
  • BBI-608

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

Experimental: BBI608 in combination with panitumumab 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

Experimental: BBI608 in combination with capecitabine Drug: BBI608
BBI608 is administered at 500 mg po bid continuously.
Other Names:
  • Napabucasin
  • BB608
  • BBI-608

Drug: Capecitabine
Capecitabine will be administered orally at 1000 mg/m2 bid daily on days 8-21 every three weeks.
Other Name: Xeloda




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. 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



Information from the National Library of Medicine

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

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.

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): NCT01776307


Locations
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United States, Arizona
Mayo Clinic
Scottsdale, Arizona, United States, 85259
United States, Colorado
USOR - Rocky Mountain Cancer Center
Denver, Colorado, United States, 80218
United States, Florida
Mayo Clinic
Jacksonville, Florida, United States, 32224
United States, Minnesota
USOR - Minnesota Oncology Hematology
Minneapolis, Minnesota, United States, 55404
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, Ohio
The Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States, 43210
United States, Oregon
USOR - Northwest Cancer Specialists
Portland, Oregon, United States, 97227
United States, Pennsylvania
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
United States, South Carolina
Institute for Translational Oncology Research, Greenville Hospital System
Greenville, South Carolina, United States, 29605
United States, Texas
USOR - Texas Oncology Dallas
Dallas, Texas, United States, 75246
US Oncology Research
The Woodlands, Texas, United States, 77380
USOR - Texas Oncology Tyler
Tyler, Texas, United States, 75702
United States, Virginia
USOR - Virginia Cancer Specialists
Fairfax, Virginia, United States, 22031
Sponsors and Collaborators
Sumitomo Dainippon Pharma Oncology, Inc
Investigators
Layout table for investigator information
Principal Investigator: William J. Edenfield, MD Institute for Translational Oncology Research, Greenville Hospital System
  Study Documents (Full-Text)

Documents provided by Sumitomo Dainippon Pharma Oncology, Inc:
Study Protocol  [PDF] October 9, 2014
Statistical Analysis Plan  [PDF] September 9, 2020

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Responsible Party: Sumitomo Dainippon Pharma Oncology, Inc
ClinicalTrials.gov Identifier: NCT01776307    
Other Study ID Numbers: BBI608-224
First Posted: January 28, 2013    Key Record Dates
Results First Posted: June 18, 2021
Last Update Posted: June 18, 2021
Last Verified: June 2021
Keywords provided by Sumitomo Dainippon Pharma Oncology, Inc:
BBI608
Additional relevant MeSH terms:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Capecitabine
Cetuximab
Panitumumab
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antineoplastic Agents, Immunological