A Study of BBI608 in Adult Patients With Advanced Colorectal Cancer

A Phase II Clinical Study of BBI608 in Adult Patients With Advanced Colorectal Cancer

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.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: BBI608; Drug: Cetuximab; Drug: Panitumumab; Drug: Capecitabine

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: Interventional
• Enrollment (Actual): 200
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic
  • Colorado
    • Denver, Colorado, United States, 80218
      • USOR - Rocky Mountain Cancer Center
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • USOR - Minnesota Oncology Hematology
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Comprehensive Cancer Center
  • Oregon
    • Portland, Oregon, United States, 97227
      • USOR - Northwest Cancer Specialists
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Abramson Cancer Center of the University of Pennsylvania
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Institute for Translational Oncology Research, Greenville Hospital System
  • Texas
    • Dallas, Texas, United States, 75246
      • USOR - Texas Oncology Dallas
    • The Woodlands, Texas, United States, 77380
      • US Oncology Research
    • Tyler, Texas, United States, 75702
      • USOR - Texas Oncology Tyler
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • USOR - Virginia Cancer Specialists

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BBI608 in combination with cetuximab	Drug: BBI608; BBI608 is administered at 500 mg po bid continuously.; Other Names: Napabucasin; BBI-608; BB608; 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 Names: Erbitux
Experimental: BBI608 in combination with panitumumab	Drug: BBI608; BBI608 is administered at 500 mg po bid continuously.; Other Names: Napabucasin; BBI-608; BB608; 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 Names: Vectibix
Experimental: BBI608 in combination with capecitabine	Drug: BBI608; BBI608 is administered at 500 mg po bid continuously.; Other Names: Napabucasin; BBI-608; BB608; Drug: Capecitabine; Capecitabine will be administered orally at 1000 mg/m2 bid daily on days 8-21 every three weeks.; Other Names: Xeloda

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Control Rate	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	From the date of first treatment, every 8 weeks, until the date of first documented objective disease progression, up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival	The effect of napabucasin given in combination with cetuximab, panitumumab or capecitabine on Progression Free Survival (PFS) of patients with advanced colorectal cancer.	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
Overall Survival	The effect of napabucasin given in combination with cetuximab, panitumumab or capecitabine on the Overall Survival of patients with advanced colorectal cancer	4 weeks after the patient has been off study treatment, every 3 months thereafter until death, up to 60 months.
Determination of the Maximum Observed Concentration (Cmax) of Napabucasin When Administered 480mg, Twice Daily, on Day 5 of 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.	Blood samples drawn on day 5 during the first study cycle
Determination of the Maximum Observed Concentration (Cmax) of Napabucasin When Administered 480mg, Twice Daily, on Day 21 of 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.	Blood samples drawn on day 21 during the first study cycle
Determination of the Maximum Observed Concentration (Cmax) of Napabucasin When Administered 240mg, Twice Daily, on Day 21 of 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.	Blood samples drawn on day 21 during the first study cycle
Determination of the Maximum Observed Concentration (Cmax) of Napabucasin When Administered 500mg, Twice Daily, on Day 5 of 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.	Blood samples drawn on day 5 during the first study cycle
Determination of the Maximum Observed Concentration (Cmax) of Napabucasin When Administered 500mg, Twice Daily, on Day 21 of 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.	Blood samples drawn on day 21 during the first study cycle
Area Under the Plasma Concentration vs. Time Curve (AUClast) of Napabucasin When Administered 480mg, Twice Daily, on Day 5 of 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.	Blood samples drawn on day 5 during the first study cycle
Area Under the Plasma Concentration vs. Time Curve (AUClast) of Napabucasin When Administered 480mg, Twice Daily, on Day 21 of 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.	Blood samples drawn on day 21 during the first study cycle
Area Under the Plasma Concentration vs. Time Curve (AUClast) of Napabucasin When Administered 240mg, Twice Daily, on Day 21 of 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.	Blood samples drawn on day 21 during the first study cycle
Area Under the Plasma Concentration vs. Time Curve (AUClast) of Napabucasin When Administered 500mg, Twice Daily, on Day 5 of 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.	Blood samples drawn on day 5 during the first study cycle
Area Under the Plasma Concentration vs. Time Curve (AUClast) of Napabucasin When Administered 500mg, Twice Daily, on Day 21 of 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.	Blood samples drawn on day 21 during the first study cycle
Pharmacodynamics	To determine the response (increase or decrease) of biomarkers from biopsied tumors following the administration of napabucasin	During the first 28 days of the study cycle
Number of Patients With Adverse Events and Serious Adverse Events	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	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.

Collaborators and Investigators

• Sponsor: Sumitomo Pharma America, Inc.
• Investigators: Principal Investigator: William J. Edenfield, MD, Institute for Translational Oncology Research, Greenville Hospital System

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (Actual): June 1, 2018
• Study Completion (Actual): April 1, 2020

Study Registration Dates

• First Submitted: January 21, 2013
• First Submitted That Met QC Criteria: January 23, 2013
• First Posted (Estimated): January 28, 2013

Study Record Updates

• Last Update Posted (Actual): November 15, 2023
• Last Update Submitted That Met QC Criteria: November 13, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: BBI608
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Antineoplastic Agents, Immunological; Capecitabine; Panitumumab; Cetuximab
• Other Study ID Numbers: BBI608-224