A Study of BBI608 in Adult Patients With Advanced Colorec... | NCT01776307

Label	Type	Intervention Names
BBI608 in combination with cetuximab	Experimental	Drug: BBI608 Drug: Cetuximab
BBI608 in combination with panitumumab	Experimental	Drug: BBI608 Drug: Panitumumab
BBI608 in combination with capecitabine	Experimental	Drug: BBI608 Drug: Capecitabine

Name	Type	Description	Arm Group Labels	Other Names
BBI608	Drug	BBI608 is administered at 500 mg po bid continuously.	BBI608 in combination with capecitabine BBI608 in combination with cetuximab BBI608 in combination with panitumumab

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

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

Name	Affiliation	Role
William J. Edenfield, MD	Institute for Translational Oncology Research, Greenville Hospital System	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Mayo Clinic		Scottsdale	Arizona	85259	United States
USOR - Rocky Mountain Cancer Center

ID	Title	Description
FG000	Napabucasin Plus Cetuximab	All participants who were enrolled to Arm A to receive napabucasin administered orally, twice daily in combination with weekly cetuximab administered intravenously
FG001	Napabucasin Plus Panitumumab

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Oct 9, 2014	May 20, 2021

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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

Patients who received at least 1 cycle of study treatment and had at least 1 disease assessment following the initiation of therapy. Patients missing imaging assessment following the initiation of treatment are not included in the assessment for DCR.

Posted

Number

95% Confidence Interval

Percentage of participants

From the date of first treatment, every 8 weeks, until the date of first documented objective disease progression, up to 24 months

ID	Title	Description
OG000	Napabucasin Plus Cetuximab	Napabucasin administered orally, twice daily, in combination with weekly cetuximab administered intravenously on Days 5, 12, 19, and 26 of each 28 day study cycle. Patients in this group had a baseline scan and at least one assessment approximately 8 weeks from baseline.
OG001	Napabucasin Plus Panitumumab	Napabucasin administered orally, twice daily, in combination with panitumumab administered intravenously on Days 8 and 22 of each 28 day study cycle. Patients in this group had a baseline scan and at least one assessment approximately 8 weeks from baseline.
OG002	Napabucasin Plus Capecitabine	Napabucasin administered orally, twice daily, in combination with capecitabine administered twice daily on Days 8-21 every three weeks. Patients in this group had a baseline scan and at least one assessment approximately 8 weeks from baseline.

Units	Counts
Participants	OG00029 OG00141 OG00239

Title

Denominators

Categories

Title	Measurements
	OG00034.5(17.9 to 54.3) OG00136.6(22.1 to 53.1) OG00225.6(13.0 to 42.1)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001 OG002																		Other	Descriptive analysis for investigational arms; no comparator analysis	The exact 95% confidence interval is based on the Clopper-Pearson method.

Secondary

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.

Posted

Median

95% Confidence Interval

months

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

ID	Title	Description
OG000	Napabucasin Plus Cetuximab	Napabucasin administered orally, twice daily, in combination with weekly cetuximab administered intravenously on Days 5, 12, 19, and 26 of each 28 day study cycle . Patients in this group had a baseline scan and at least one on study scan or died from any cause.
OG001	Napabucasin Plus Panitumumab	Napabucasin administered orally, twice daily, in combination with panitumumab administered intravenously on Days 8 and 22 of each 28 day study cycle. Patients in this group had a baseline scan and at least one on study scan or died from any cause.
OG002	Napabucasin Plus Capecitabine	Napabucasin administered orally, twice daily, in combination with capecitabine administered twice daily on Days 8-21 every three weeks. Patients in this group had a baseline scan and at least one on study scan or died from any cause

Secondary

Overall Survival

The effect of napabucasin given in combination with cetuximab, panitumumab or capecitabine on the Overall Survival of patients with advanced colorectal cancer

Posted

Median

95% Confidence Interval

Months

4 weeks after the patient has been off study treatment, every 3 months thereafter until death, up to 60 months.

ID	Title	Description
OG000	Napabucasin Plus Cetuximab	Napabucasin administered orally, twice daily, in combination with weekly cetuximab administered intravenously on Days 5, 12, 19, and 26 of each 28 day study cycle.
OG001	Napabucasin Plus Panitumumab	Napabucasin administered orally, twice daily, in combination with panitumumab administered intravenously on Days 8 and 22 of each 28 day study cycle.
OG002	Napabucasin Plus Capecitabine	Napabucasin administered orally, twice daily, in combination with capecitabine administered twice daily on Days 8-21 every three weeks.

Units	Counts

Secondary

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.

Napabucasin plus capecitabine: No evaluable patients dosed at 480mg twice daily.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Blood samples drawn on day 5 during the first study cycle

ID	Title	Description
OG000	Napabucasin Plus Cetuximab	Napabucasin administered orally, twice daily, in combination with weekly cetuximab administered intravenously on Days 5, 12, 19, and 26 of each 28 day study cycle. Patients included in this group took napabucasin 480mg twice daily and provided blood samples for analysis.
OG001	Napabucasin Plus Panitumumab	Napabucasin administered orally, twice daily, in combination with panitumumab administered intravenously on Days 8 and 22 of each 28 day study cycle. Patients included in this group took napabucasin 480mg twice daily and provided blood samples for analysis.
OG002	Napabucasin Plus Capecitabine

Secondary

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.

Napabucasin plus capecitabine: No evaluable patients dosed at 480mg twice daily.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Blood samples drawn on day 21 during the first study cycle

ID	Title	Description
OG000	Napabucasin Plus Cetuximab	Napabucasin administered orally, twice daily, in combination with weekly cetuximab administered intravenously on Days 5, 12, 19, and 26 of each 28 day study cycle. Patients included in this group took napabucasin 480mg twice daily and provided blood samples for analysis.
OG001	Napabucasin Plus Panitumumab	Napabucasin administered orally, twice daily, in combination with panitumumab administered intravenously on Days 8 and 22 of each 28 day study cycle. Patients included in this group took napabucasin 480mg twice daily and provided blood samples for analysis.
OG002	Napabucasin Plus Capecitabine

Secondary

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.

Napabucasin plus panitumumab & Napabucasin plus capecitabine: No evaluable patients dosed at 240mg twice daily.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Blood samples drawn on day 21 during the first study cycle

ID	Title	Description
OG000	Napabucasin Plus Cetuximab	Napabucasin administered orally, twice daily, in combination with weekly cetuximab administered intravenously on Days 5, 12, 19, and 26 of each 28 day study cycle. Patients included in this group took napabucasin 240mg twice daily and provided blood samples for analysis.
OG001	Napabucasin Plus Panitumumab	Napabucasin administered orally, twice daily, in combination with panitumumab administered intravenously on Days 8 and 22 of each 28 day study cycle. Patients included in this group took napabucasin 240mg twice daily and provided blood samples for analysis.
OG002	Napabucasin Plus Capecitabine

Secondary

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.

Napabucasin plus cetuximab: No evaluable patients dosed at 500mg twice daily.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Blood samples drawn on day 5 during the first study cycle

ID	Title	Description
OG000	Napabucasin Plus Cetuximab	Napabucasin administered orally, twice daily, in combination with weekly cetuximab administered intravenously on Days 5, 12, 19, and 26 of each 28 day study cycle. Patients included in this group took napabucasin 500mg twice daily and provided blood samples for analysis.
OG001	Napabucasin Plus Panitumumab	Napabucasin administered orally, twice daily, in combination with panitumumab administered intravenously on Days 8 and 22 of each 28 day study cycle. Patients included in this group took napabucasin 500mg twice daily and provided blood samples for analysis.
OG002	Napabucasin Plus Capecitabine

Secondary

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.

Napabucasin plus cetuximab: No evaluable patients dosed at 500mg twice daily.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Blood samples drawn on day 21 during the first study cycle

ID	Title	Description
OG000	Napabucasin Plus Cetuximab	Napabucasin administered orally, twice daily, in combination with weekly cetuximab administered intravenously on Days 5, 12, 19, and 26 of each 28 day study cycle. Patients included in this group took napabucasin 500mg twice daily and provided blood samples for analysis.
OG001	Napabucasin Plus Panitumumab	Napabucasin administered orally, twice daily, in combination with panitumumab administered intravenously on Days 8 and 22 of each 28 day study cycle. Patients included in this group took napabucasin 500mg twice daily and provided blood samples for analysis.
OG002	Napabucasin Plus Capecitabine

Secondary

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.

Napabucasin plus capecitabine: No evaluable patients dosed at 480mg twice daily.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*ng/mL

Blood samples drawn on day 5 during the first study cycle

ID	Title	Description
OG000	Napabucasin Plus Cetuximab	Napabucasin administered orally, twice daily, in combination with weekly cetuximab administered intravenously on Days 5, 12, 19, and 26 of each 28 day study cycle. Patients included in this group took napabucasin 480mg twice daily and provided blood samples for analysis.
OG001	Napabucasin Plus Panitumumab	Napabucasin administered orally, twice daily, in combination with panitumumab administered intravenously on Days 8 and 22 of each 28 day study cycle. Patients included in this group took napabucasin 480mg twice daily and provided blood samples for analysis.
OG002	Napabucasin Plus Capecitabine

Secondary

Area Under the Plasma Concentration vs. Time Curve (AUClast) of Napabucasin When Administered 480mg, Twice Daily, on Day 21 of the First Study Cycle

Napabucasin plus capecitabine: No evaluable patients dosed at 480mg twice daily.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*ng/mL

Blood samples drawn on day 21 during the first study cycle

ID	Title	Description
OG000	Napabucasin Plus Cetuximab	Napabucasin administered orally, twice daily, in combination with weekly cetuximab administered intravenously on Days 5, 12, 19, and 26 of each 28 day study cycle. Patients included in this group took napabucasin 480mg twice daily and provided blood samples for analysis.
OG001	Napabucasin Plus Panitumumab	Napabucasin administered orally, twice daily, in combination with panitumumab administered intravenously on Days 8 and 22 of each 28 day study cycle. Patients included in this group took napabucasin 480mg twice daily and provided blood samples for analysis.
OG002	Napabucasin Plus Capecitabine

Secondary

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.

Napabucasin plus panitumumab and Napabucasin plus capecitabine: No evaluable patients dosed at 240mg twice daily.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*ng/mL

Blood samples drawn on day 21 during the first study cycle

ID	Title	Description
OG000	Napabucasin Plus Cetuximab	Napabucasin administered orally, twice daily, in combination with weekly cetuximab administered intravenously on Days 5, 12, 19, and 26 of each 28 day study cycle. Patients included in this group took napabucasin 240mg twice daily and provided blood samples for analysis.
OG001	Napabucasin Plus Panitumumab	Napabucasin administered orally, twice daily, in combination with panitumumab administered intravenously on Days 8 and 22 of each 28 day study cycle. Patients included in this group took napabucasin 240mg twice daily and provided blood samples for analysis.
OG002	Napabucasin Plus Capecitabine

Secondary

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.

Napabucasin plus cetuximab: No evaluable patients dosed at 500mg twice daily.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*ng/mL

Blood samples drawn on day 5 during the first study cycle

ID	Title	Description
OG000	Napabucasin Plus Cetuximab	Napabucasin administered orally, twice daily, in combination with weekly cetuximab administered intravenously on Days 5, 12, 19, and 26 of each 28 day study cycle. Patients included in this group took napabucasin 500mg twice daily and provided blood samples for analysis.
OG001	Napabucasin Plus Panitumumab	Napabucasin administered orally, twice daily, in combination with panitumumab administered intravenously on Days 8 and 22 of each 28 day study cycle. Patients included in this group took napabucasin 500mg twice daily and provided blood samples for analysis.
OG002	Napabucasin Plus Capecitabine

Secondary

Area Under the Plasma Concentration vs. Time Curve (AUClast) of Napabucasin When Administered 500mg, Twice Daily, on Day 21 of the First Study Cycle

Napabucasin plus cetuximab: No evaluable patients dosed at 500mg twice daily.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*ng/mL

Blood samples drawn on day 21 during the first study cycle

ID	Title	Description
OG000	Napabucasin Plus Cetuximab	Napabucasin administered orally, twice daily, in combination with weekly cetuximab administered intravenously on Days 5, 12, 19, and 26 of each 28 day study cycle. Patients included in this group took napabucasin 500mg twice daily and provided blood samples for analysis.
OG001	Napabucasin Plus Panitumumab	Napabucasin administered orally, twice daily, in combination with panitumumab administered intravenously on Days 8 and 22 of each 28 day study cycle. Patients included in this group took napabucasin 500mg twice daily and provided blood samples for analysis.
OG002	Napabucasin Plus Capecitabine

Secondary

Pharmacodynamics

To determine the response (increase or decrease) of biomarkers from biopsied tumors following the administration of napabucasin

No on-treatment biopsies were performed therefore no pharmacodynamic testing on tumor tissue was conducted.

Posted

During the first 28 days of the study cycle

ID	Title	Description
OG000	Napabucasin Plus Cetuximab	Napabucasin administered orally, twice daily, in combination with weekly cetuximab administered intravenously on Days 5, 12, 19, and 26 of each 28 day study cycle . Patients included in this group needed to have on treatment biopsy
OG001	Napabucasin Plus Panitumumab	Napabucasin administered orally, twice daily, in combination with panitumumab administered intravenously on Days 8 and 22 of each 28 day study cycle. Patients included in this group needed to have on treatment biopsy
OG002	Napabucasin Plus Capecitabine	Napabucasin administered orally, twice daily, in combination with capecitabine administered twice daily on Days 8-21 every three weeks. Patients included in this group needed to have on treatment biopsy.

Secondary

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

Posted

Count of Participants

Participants

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.

ID	Title	Description
OG000	Napabucasin Plus Cetuximab	Napabucasin administered orally, twice daily, in combination with weekly cetuximab administered intravenously on Days 5, 12, 19, and 26 of each 28 day study cycle. Patients included in this group received at least one dose of study drug.
OG001	Napabucasin Plus Panitumumab	Napabucasin administered orally, twice daily, in combination with panitumumab administered intravenously on Days 8 and 22 of each 28 day study cycle. Patients included in this group received at least one dose of study drug.
OG002	Napabucasin Plus Capecitabine	Napabucasin administered orally, twice daily, in combination with capecitabine administered twice daily on Days 8-21 every three weeks. Patients included in this group received at least one dose of study drug.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal pain	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0004 affected49 at risk EG0014 affected75 at risk EG0025 affected75 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0004 affected49 at risk EG0010 affected75 at risk EG0022 affected75 at risk
Nausea	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected49 at risk EG0011 affected75 at risk EG0020 affected75 at risk
Constipation	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected49 at risk EG0010 affected75 at risk EG0021 affected75 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected49 at risk EG0012 affected75 at risk EG0021 affected75 at risk
Large intestine perforation	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected49 at risk EG0010 affected75 at risk EG0020 affected75 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected49 at risk EG0013 affected75 at risk EG0022 affected75 at risk
Vomiting	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected49 at risk EG0012 affected75 at risk EG0022 affected75 at risk
Ascites	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected49 at risk EG0011 affected75 at risk EG0020 affected75 at risk
Colitis	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected49 at risk EG0011 affected75 at risk EG0020 affected75 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected49 at risk EG0011 affected75 at risk EG0021 affected75 at risk
Pancreatitis acute	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected49 at risk EG0010 affected75 at risk EG0021 affected75 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected49 at risk EG0011 affected75 at risk EG0021 affected75 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected49 at risk EG0010 affected75 at risk EG0020 affected75 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected49 at risk EG0012 affected75 at risk EG0020 affected75 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected49 at risk EG0010 affected75 at risk EG0023 affected75 at risk
Disease progression	General disorders	MedDRA 18.0	Systematic Assessment	EG0003 affected49 at risk EG0013 affected75 at risk EG0020 affected75 at risk
Pyrexia	General disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected49 at risk EG0013 affected75 at risk EG0020 affected75 at risk
Chest pain	General disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected49 at risk EG0011 affected75 at risk EG0020 affected75 at risk
Device dislocation	General disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected49 at risk EG0011 affected75 at risk EG0020 affected75 at risk
Oedema peripheral	General disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected49 at risk EG0011 affected75 at risk EG0020 affected75 at risk
Asthenia	General disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected49 at risk EG0010 affected75 at risk EG0021 affected75 at risk
Pain	General disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected49 at risk EG0010 affected75 at risk EG0021 affected75 at risk
Bile duct obstruction	Hepatobiliary disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected49 at risk EG0010 affected75 at risk EG0023 affected75 at risk
Hepatic failure	Hepatobiliary disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected49 at risk EG0010 affected75 at risk EG0020 affected75 at risk
Cholangitis	Hepatobiliary disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected49 at risk EG0011 affected75 at risk EG0021 affected75 at risk
Hyperbilirubinaemia	Hepatobiliary disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected49 at risk EG0011 affected75 at risk EG0021 affected75 at risk
Anaphylactic reaction	Immune system disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected49 at risk EG0010 affected75 at risk EG0020 affected75 at risk
Sepsis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected49 at risk EG0012 affected75 at risk EG0021 affected75 at risk
Clostridium difficile infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected49 at risk EG0011 affected75 at risk EG0021 affected75 at risk
Urinary tract infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected49 at risk EG0011 affected75 at risk EG0020 affected75 at risk
Pneumonia	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected49 at risk EG0010 affected75 at risk EG0022 affected75 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected49 at risk EG0013 affected75 at risk EG0022 affected75 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected49 at risk EG0011 affected75 at risk EG0020 affected75 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected49 at risk EG0011 affected75 at risk EG0020 affected75 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected49 at risk EG0010 affected75 at risk EG0021 affected75 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected49 at risk EG0011 affected75 at risk EG0020 affected75 at risk
Flank pain	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected49 at risk EG0011 affected75 at risk EG0020 affected75 at risk
Pain in jaw	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected49 at risk EG0011 affected75 at risk EG0020 affected75 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected49 at risk EG0010 affected75 at risk EG0021 affected75 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected49 at risk EG0012 affected75 at risk EG0023 affected75 at risk
Haematuria	Renal and urinary disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected49 at risk EG0011 affected75 at risk EG0020 affected75 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected49 at risk EG0011 affected75 at risk EG0020 affected75 at risk
Pericardial effusion	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected49 at risk EG0011 affected75 at risk EG0020 affected75 at risk
Blood bilirubin increased	Investigations	MedDRA 18.0	Systematic Assessment	EG0000 affected49 at risk EG0011 affected75 at risk EG0020 affected75 at risk
Blood creatinine increased	Investigations	MedDRA 18.0	Systematic Assessment	EG0000 affected49 at risk EG0011 affected75 at risk EG0020 affected75 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected49 at risk EG0011 affected75 at risk EG0020 affected75 at risk
Skin disorder	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected49 at risk EG0011 affected75 at risk EG0020 affected75 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected49 at risk EG0011 affected75 at risk EG0020 affected75 at risk
Renal haematoma	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0000 affected49 at risk EG0011 affected75 at risk EG0020 affected75 at risk
Haemorrhage intracranial	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected49 at risk EG0011 affected75 at risk EG0020 affected75 at risk
Hemiparesis	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected49 at risk EG0010 affected75 at risk EG0021 affected75 at risk
Hepatic encephalopathy	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected49 at risk EG0010 affected75 at risk EG0021 affected75 at risk
Hypotension	Vascular disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected49 at risk EG0010 affected75 at risk EG0021 affected75 at risk
Thrombosis	Vascular disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected49 at risk EG0010 affected75 at risk EG0021 affected75 at risk
Malignant neoplasm progression	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Systematic Assessment	EG0000 affected49 at risk EG0010 affected75 at risk EG0021 affected75 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhoea	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG00037 affected49 at risk EG00158 affected75 at risk EG00261 affected75 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG00025 affected49 at risk EG00126 affected75 at risk EG00230 affected75 at risk
Nausea	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG00022 affected49 at risk EG00139 affected75 at risk EG00247 affected75 at risk
Vomiting	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG00022 affected49 at risk EG00127 affected75 at risk EG00227 affected75 at risk
Constipation	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG00015 affected49 at risk EG0019 affected75 at risk EG00210 affected75 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0006 affected49 at risk EG0016 affected75 at risk EG0027 affected75 at risk
Ascites	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected49 at risk EG0015 affected75 at risk EG0023 affected75 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0003 affected49 at risk EG0013 affected75 at risk EG0026 affected75 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected49 at risk EG0015 affected75 at risk EG0024 affected75 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment	EG00015 affected49 at risk EG00124 affected75 at risk EG00223 affected75 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment	EG00015 affected49 at risk EG00123 affected75 at risk EG0024 affected75 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment	EG00012 affected49 at risk EG00123 affected75 at risk EG00215 affected75 at risk
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment	EG0008 affected49 at risk EG0018 affected75 at risk EG00218 affected75 at risk
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment	EG0007 affected49 at risk EG0015 affected75 at risk EG0020 affected75 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment	EG0006 affected49 at risk EG0017 affected75 at risk EG00210 affected75 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment	EG0005 affected49 at risk EG0012 affected75 at risk EG00212 affected75 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment	EG0004 affected49 at risk EG00115 affected75 at risk EG00222 affected75 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected49 at risk EG0015 affected75 at risk EG0022 affected75 at risk
Hypouricaemia	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment	EG00010 affected49 at risk EG0014 affected75 at risk EG0020 affected75 at risk
Dermatitis acneiform	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG00010 affected49 at risk EG00113 affected75 at risk EG0020 affected75 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG00010 affected49 at risk EG0016 affected75 at risk EG0023 affected75 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0009 affected49 at risk EG00121 affected75 at risk EG0025 affected75 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0006 affected49 at risk EG0019 affected75 at risk EG0021 affected75 at risk
Palmar-plantar erythrodysaethesia syndrome	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected49 at risk EG0015 affected75 at risk EG00211 affected75 at risk
Fatigue	General disorders	MedDRA 18.0	Systematic Assessment	EG00020 affected49 at risk EG00143 affected75 at risk EG00236 affected75 at risk
Oedema peripheral	General disorders	MedDRA 18.0	Systematic Assessment	EG0006 affected49 at risk EG0016 affected75 at risk EG0028 affected75 at risk
Pyrexia	General disorders	MedDRA 18.0	Systematic Assessment	EG0006 affected49 at risk EG0015 affected75 at risk EG0027 affected75 at risk
Mucosal inflammation	General disorders	MedDRA 18.0	Systematic Assessment	EG0005 affected49 at risk EG0013 affected75 at risk EG0023 affected75 at risk
Chills	General disorders	MedDRA 18.0	Systematic Assessment	EG0003 affected49 at risk EG0016 affected75 at risk EG0023 affected75 at risk
Disease progression	General disorders	MedDRA 18.0	Systematic Assessment	EG0003 affected49 at risk EG0013 affected75 at risk EG0020 affected75 at risk
Asthenia	General disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected49 at risk EG0015 affected75 at risk EG0027 affected75 at risk
Dizziness	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0007 affected49 at risk EG0017 affected75 at risk EG0029 affected75 at risk
Headache	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0005 affected49 at risk EG0016 affected75 at risk EG0023 affected75 at risk
Chromaturia	Renal and urinary disorders	MedDRA 18.0	Systematic Assessment	EG00011 affected49 at risk EG00112 affected75 at risk EG00210 affected75 at risk
Proteinuria	Renal and urinary disorders	MedDRA 18.0	Systematic Assessment	EG0005 affected49 at risk EG00111 affected75 at risk EG00218 affected75 at risk
Ketonuria	Renal and urinary disorders	MedDRA 18.0	Systematic Assessment	EG0003 affected49 at risk EG00111 affected75 at risk EG00217 affected75 at risk
Haematuria	Renal and urinary disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected49 at risk EG0019 affected75 at risk EG00210 affected75 at risk
Glycosuria	Renal and urinary disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected49 at risk EG0012 affected75 at risk EG0026 affected75 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA 18.0	Systematic Assessment	EG0009 affected49 at risk EG00116 affected75 at risk EG00216 affected75 at risk
Lymphopenia	Blood and lymphatic system disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected49 at risk EG0019 affected75 at risk EG00218 affected75 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected49 at risk EG0016 affected75 at risk EG0025 affected75 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected49 at risk EG0014 affected75 at risk EG0025 affected75 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA 18.0	Systematic Assessment	EG0007 affected49 at risk EG0019 affected75 at risk EG00212 affected75 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 18.0	Systematic Assessment	EG0006 affected49 at risk EG0016 affected75 at risk EG00213 affected75 at risk
Blood bilirubin increased	Investigations	MedDRA 18.0	Systematic Assessment	EG0004 affected49 at risk EG0016 affected75 at risk EG0021 affected75 at risk
Alanine aminotransferase increased	Investigations	MedDRA 18.0	Systematic Assessment	EG0004 affected49 at risk EG0015 affected75 at risk EG0025 affected75 at risk
Blood lactate dehydrogenase increased	Investigations	MedDRA 18.0	Systematic Assessment	EG0004 affected49 at risk EG0011 affected75 at risk EG0020 affected75 at risk
Blood creatinine increased	Investigations	MedDRA 18.0	Systematic Assessment	EG0003 affected49 at risk EG0011 affected75 at risk EG0025 affected75 at risk
Weight decreased	Investigations	MedDRA 18.0	Systematic Assessment	EG0001 affected49 at risk EG0015 affected75 at risk EG0025 affected75 at risk
Protein total decreased	Investigations	MedDRA 18.0	Systematic Assessment	EG0000 affected49 at risk EG0015 affected75 at risk EG0020 affected75 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0007 affected49 at risk EG00113 affected75 at risk EG00213 affected75 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected49 at risk EG0019 affected75 at risk EG00210 affected75 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected49 at risk EG0014 affected75 at risk EG0020 affected75 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected49 at risk EG0011 affected75 at risk EG0025 affected75 at risk
Urinary tract infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0004 affected49 at risk EG00115 affected75 at risk EG0026 affected75 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0004 affected49 at risk EG0016 affected75 at risk EG0025 affected75 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0004 affected49 at risk EG0014 affected75 at risk EG0025 affected75 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0004 affected49 at risk EG0011 affected75 at risk EG0022 affected75 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0003 affected49 at risk EG0012 affected75 at risk EG0022 affected75 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0003 affected49 at risk EG0011 affected75 at risk EG0023 affected75 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected49 at risk EG0012 affected75 at risk EG0024 affected75 at risk
Vision blurred	Eye disorders	MedDRA 18.0	Systematic Assessment	EG0004 affected49 at risk EG0010 affected75 at risk EG0020 affected75 at risk
Insomnia	Psychiatric disorders	MedDRA 18.0	Systematic Assessment	EG0004 affected49 at risk EG0013 affected75 at risk EG0023 affected75 at risk
Anxiety	Psychiatric disorders	MedDRA 18.0	Systematic Assessment	EG0003 affected49 at risk EG0013 affected75 at risk EG0023 affected75 at risk
Depression	Psychiatric disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected49 at risk EG0015 affected75 at risk EG0024 affected75 at risk
Hypotension	Vascular disorders	MedDRA 18.0	Systematic Assessment	EG0003 affected49 at risk EG0014 affected75 at risk EG0023 affected75 at risk
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0003 affected49 at risk EG0011 affected75 at risk EG0020 affected75 at risk
Hyperbilirubinaemia	Hepatobiliary disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected49 at risk EG0011 affected75 at risk EG0027 affected75 at risk

ID	Title	Description
BG000	Napabucasin Plus Cetuximab	All participants who were enrolled to Arm A to receive napabucasin administered orally, twice daily in combination with weekly cetuximab administered intravenously
BG001	Napabucasin Plus Panitumumab	All participants who were enrolled to Arm B to receive napabucasin administered orally, twice daily in combination with panitumumab administered intravenously on day 8 and 22 of each 28 day cycle
BG002	Napabucasin Plus Capecitabine	All participants who were enrolled to Arm C to receive napabucasin administered orally, twice daily in combination with capecitabine administered twice daily on days 8-21 every three weeks
BG003	Total	Total of all reporting groups

ID	Term
D007414	Intestinal Neoplasms
D005770	Gastrointestinal Neoplasms
D004067	Digestive System Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D004066	Digestive System Diseases
D005767	Gastrointestinal Diseases
D003108	Colonic Diseases
D007410	Intestinal Diseases
D012002	Rectal Diseases

ID	Term
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins
D003841	Deoxycytidine
D003562	Cytidine
D011741	Pyrimidine Nucleosides
D011743	Pyrimidines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D005472	Fluorouracil
D014498	Uracil
D011744	Pyrimidinones
D003853	Deoxyribonucleosides
D009705	Nucleosides
D009706	Nucleic Acids, Nucleotides, and Nucleosides

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Napabucasin Plus Cetuximab	All participants who received at least 1 dose of napabucasin administered orally, twice daily in combination with weekly cetuximab administered intravenously	45	49	17	49	49	49
EG001	Napabucasin Plus Panitumumab	All participants who received at least 1 dose of napabucasin administered orally, twice daily in combination with panitumumab administered intravenously on day 8 and 22 of each 28 day cycle	70	75	29	75	75	75
EG002	Napabucasin Plus Capecitabine	All participants who received at least 1 dose of napabucasin administered orally, twice daily in combination with capecitabine administered twice daily on days 8-21 every three weeks	72	75	26	75	75	75

ID	Term
C000621033	napabucasin
D000077544	Panitumumab
D000069287	Capecitabine
D000068818	Cetuximab