Trial Outcomes & Findings for BBI608 and Best Supportive Care vs Placebo and Best Supportive Care in Pretreated Advanced Colorectal Carcinoma (NCT NCT01830621)

NCT ID: NCT01830621

Last Updated: 2023-08-28

Results Overview

Time from the day of randomization to death. For alive patients, overall survival was censored at the last day the patient was known alive (LKA).

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 282 participants
• Primary outcome timeframe: 36 month
• Results posted on: 2023-08-28

Participant Flow

Participant milestones

Measure	BBI608 BBI608 480 mg two times daily (960 mg total daily dose)+ Best Supportive Care BBI608 Best Supportive Care	Placebo Placebo two times daily + Best Supportive Care Placebo Best Supportive Care
Overall Study STARTED	138	144
Overall Study COMPLETED	138	144
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

BBI608 and Best Supportive Care vs Placebo and Best Supportive Care in Pretreated Advanced Colorectal Carcinoma

Baseline characteristics by cohort

Measure	BBI608 n=138 Participants BBI608 480 mg two times daily (960 mg total daily dose)+ Best Supportive Care BBI608 Best Supportive Care	Placebo n=144 Participants Placebo two times daily + Best Supportive Care Placebo Best Supportive Care	Total n=282 Participants Total of all reporting groups
Age, Continuous	64 years n=5 Participants	64 years n=7 Participants	64 years n=5 Participants
Sex: Female, Male Female	47 Participants n=5 Participants	51 Participants n=7 Participants	98 Participants n=5 Participants
Sex: Female, Male Male	91 Participants n=5 Participants	93 Participants n=7 Participants	184 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	26 Participants n=5 Participants	34 Participants n=7 Participants	60 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	112 Participants n=5 Participants	107 Participants n=7 Participants	219 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment Canada	64 participants n=5 Participants	77 participants n=7 Participants	141 participants n=5 Participants
Region of Enrollment Japan	22 participants n=5 Participants	22 participants n=7 Participants	44 participants n=5 Participants
Region of Enrollment Australia	52 participants n=5 Participants	45 participants n=7 Participants	97 participants n=5 Participants
ECOG (Eastern Cooperative Oncology Group) Performance Status 0	37 Participants n=5 Participants	42 Participants n=7 Participants	79 Participants n=5 Participants
ECOG (Eastern Cooperative Oncology Group) Performance Status 1	101 Participants n=5 Participants	102 Participants n=7 Participants	203 Participants n=5 Participants

PRIMARY outcome

Timeframe: 36 month

Population: All patients who were randomized to this study.

Time from the day of randomization to death. For alive patients, overall survival was censored at the last day the patient was known alive (LKA).

Outcome measures

Measure	BBI608 n=138 Participants BBI608 480 mg two times daily (960 mg total daily dose)+ Best Supportive Care BBI608 Best Supportive Care	Placebo n=144 Participants Placebo two times daily + Best Supportive Care Placebo Best Supportive Care
Overall Survival	4.44 Months Interval 3.68 to 4.9	4.76 Months Interval 4.01 to 5.32

SECONDARY outcome

Timeframe: 36 months

Population: All patients randomized to this study

Defined as the time from randomization to the first objective documentation of disease progression or death due to any cause.

Outcome measures

Measure	BBI608 n=138 Participants BBI608 480 mg two times daily (960 mg total daily dose)+ Best Supportive Care BBI608 Best Supportive Care	Placebo n=144 Participants Placebo two times daily + Best Supportive Care Placebo Best Supportive Care
Progression Free Survival	1.82 Months Interval 1.74 to 1.87	1.82 Months Interval 1.74 to 1.84

SECONDARY outcome

Timeframe: 36 months

Population: All patients randomized to this study

Proportion of all randomized patients with a documented complete response (CR) defined as disappearance of all target lesions, partial response (PR) defined as >=30% decrease in the sum of the longest diameter of target lesions, and stable disease (SD) defined as <30% decrease but also <20% increase in the sum of the longest diameter of target lesions without new lesions per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) 1.1 for target lesion.

Outcome measures

Measure	BBI608 n=138 Participants BBI608 480 mg two times daily (960 mg total daily dose)+ Best Supportive Care BBI608 Best Supportive Care	Placebo n=144 Participants Placebo two times daily + Best Supportive Care Placebo Best Supportive Care
Disease Control Rate	17 Participants	18 Participants

SECONDARY outcome

Timeframe: 36 months

Population: All patients who have received at least one dose of BBI608/Placebo.

Number of patients with at least one adverse event as assessed by NCI CTCAE Version 3.0 criteria.

Outcome measures

Measure	BBI608 n=136 Participants BBI608 480 mg two times daily (960 mg total daily dose)+ Best Supportive Care BBI608 Best Supportive Care	Placebo n=144 Participants Placebo two times daily + Best Supportive Care Placebo Best Supportive Care
Number of Patients With Adverse Events	135 Participants	139 Participants

SECONDARY outcome

Timeframe: 8 weeks

Population: Patients who were assessed Quality of Life at baseline and week 8 from randomization.

Change scores from baseline at time 2 (8 weeks) from baseline for the global health status/quality of life scale scores (between 0 and 100 with higher value indicating better quality of life) as derived from responses of patients to the EORTC (European Organisation for Research and Treatment of Cancer) quality of life questionnaire (QLQ-C30).

Outcome measures

Measure	BBI608 n=55 Participants BBI608 480 mg two times daily (960 mg total daily dose)+ Best Supportive Care BBI608 Best Supportive Care	Placebo n=61 Participants Placebo two times daily + Best Supportive Care Placebo Best Supportive Care
Change of Global Quality of Life at 8 Weeks From Baseline	-10.61 units on a scale Standard Deviation 23.1	-10.66 units on a scale Standard Deviation 17.07

Adverse Events

BBI608

Serious events: 40 serious events

Other events: 134 other events

Deaths: 127 deaths

Placebo

Serious events: 29 serious events

Other events: 137 other events

Deaths: 130 deaths

Serious adverse events

Measure	BBI608 n=136 participants at risk BBI608 480 mg two times daily (960 mg total daily dose)+ Best Supportive Care BBI608 Best Supportive Care At risk patients included only patients who received at least one dose of BBI608	Placebo n=144 participants at risk Placebo two times daily + Best Supportive Care Placebo Best Supportive Care At risk patients included only patients who received at least one dose of placebo
Blood and lymphatic system disorders Anemia	0.74% 1/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	0.69% 1/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Cardiac disorders Atrial fibrillation	0.00% 0/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	0.69% 1/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Cardiac disorders Chest pain - cardiac	0.74% 1/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	0.69% 1/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Cardiac disorders Sinus tachycardia	0.74% 1/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	0.00% 0/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Cardiac disorders Supraventricular tachycardia	0.74% 1/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	0.00% 0/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Gastrointestinal disorders Abdominal pain	3.7% 5/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	0.00% 0/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Gastrointestinal disorders Bloating	0.00% 0/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	2.1% 3/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Gastrointestinal disorders Colitis	0.00% 0/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	0.69% 1/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Gastrointestinal disorders Colonic obstruction	0.74% 1/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	0.69% 1/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Gastrointestinal disorders Constipation	0.74% 1/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	0.00% 0/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Gastrointestinal disorders Diarrhea	4.4% 6/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	0.69% 1/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Gastrointestinal disorders Ileal obstruction	0.00% 0/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	0.00% 0/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Gastrointestinal disorders Ileus	0.00% 0/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	0.69% 1/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Gastrointestinal disorders Jejunal obstruction	0.74% 1/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	1.4% 2/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Gastrointestinal disorders Lower gastrointestinal hemorrhage	0.74% 1/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	0.00% 0/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Gastrointestinal disorders Nausea	0.74% 1/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	0.00% 0/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Gastrointestinal disorders Pancreatitis	0.74% 1/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	1.4% 2/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Gastrointestinal disorders Small intestinal obstruction	1.5% 2/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	0.00% 0/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Gastrointestinal disorders Upper gastrointestinal hemorrhage	0.74% 1/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	2.1% 3/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Gastrointestinal disorders Vomiting	1.5% 2/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	0.00% 0/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
General disorders Edema limbs	0.00% 0/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	1.4% 2/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
General disorders Edema trunk	0.00% 0/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	0.69% 1/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
General disorders Fatigue	1.5% 2/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	0.69% 1/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
General disorders Fever	0.00% 0/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	0.69% 1/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
General disorders Malaise	0.74% 1/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	1.4% 2/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
General disorders Non-cardiac chest pain	0.74% 1/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	0.00% 0/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Hepatobiliary disorders Other hepatobiliary disorders	0.74% 1/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	0.69% 1/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Infections and infestations Biliary tract infection	2.2% 3/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	0.69% 1/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Infections and infestations Kidney infection	0.74% 1/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	0.69% 1/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Infections and infestations Lung infection	0.74% 1/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	0.00% 0/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Infections and infestations Other infections and infestations	1.5% 2/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	0.00% 0/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Infections and infestations Sepsis	0.74% 1/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	0.00% 0/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Infections and infestations Skin infection	0.00% 0/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	1.4% 2/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Infections and infestations Upper respiratory infection	0.00% 0/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	0.69% 1/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Infections and infestations Urinary tract infection	0.74% 1/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	0.69% 1/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Injury, poisoning and procedural complications Fall	0.74% 1/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	0.69% 1/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Injury, poisoning and procedural complications Intestinal stoma obstruction	0.74% 1/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	0.69% 1/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Investigations Blood bilirubin increased	0.74% 1/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	0.00% 0/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Investigations Weight loss	0.00% 0/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	0.69% 1/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Metabolism and nutrition disorders Anorexia	1.5% 2/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	0.69% 1/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Metabolism and nutrition disorders Dehydration	5.1% 7/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	0.69% 1/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Metabolism and nutrition disorders Hyperkalemia	0.74% 1/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	1.4% 2/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Musculoskeletal and connective tissue disorders Back pain	0.74% 1/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	0.00% 0/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	0.74% 1/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	0.00% 0/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Nervous system disorders Dizziness	0.74% 1/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	0.00% 0/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Psychiatric disorders Confusion	1.5% 2/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	0.00% 0/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Renal and urinary disorders Acute kidney injury	1.5% 2/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	0.00% 0/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Renal and urinary disorders Other renal and urinary disorders	0.74% 1/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	0.69% 1/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Reproductive system and breast disorders Pelvic pain	0.74% 1/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	0.00% 0/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Respiratory, thoracic and mediastinal disorders Dyspnea	0.74% 1/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	0.00% 0/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	0.69% 1/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.74% 1/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	1.4% 2/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Respiratory, thoracic and mediastinal disorders Tracheal stenosis	0.74% 1/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	0.00% 0/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Vascular disorders Hypotension	0.74% 1/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	0.00% 0/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Vascular disorders Thromboembolic event	0.74% 1/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	0.00% 0/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.

Other adverse events

Measure	BBI608 n=136 participants at risk BBI608 480 mg two times daily (960 mg total daily dose)+ Best Supportive Care BBI608 Best Supportive Care At risk patients included only patients who received at least one dose of BBI608	Placebo n=144 participants at risk Placebo two times daily + Best Supportive Care Placebo Best Supportive Care At risk patients included only patients who received at least one dose of placebo
Gastrointestinal disorders Abdominal pain	47.1% 64/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	38.9% 56/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Gastrointestinal disorders Bloating	5.9% 8/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	6.2% 9/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Gastrointestinal disorders Constipation	35.3% 48/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	41.7% 60/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Gastrointestinal disorders Diarrhea	86.0% 117/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	31.9% 46/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Gastrointestinal disorders Dry mouth	8.1% 11/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	4.9% 7/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Gastrointestinal disorders Dyspepsia	5.9% 8/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	11.8% 17/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Gastrointestinal disorders Gastroesophageal reflux disease	7.4% 10/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	8.3% 12/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Gastrointestinal disorders Nausea	62.5% 85/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	46.5% 67/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Gastrointestinal disorders Other gastrointestinal disorders	3.7% 5/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	7.6% 11/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Gastrointestinal disorders Vomiting	44.1% 60/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	34.7% 50/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
General disorders Edema limbs	14.7% 20/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	20.1% 29/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
General disorders Fatigue	67.6% 92/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	65.3% 94/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
General disorders Fever	8.8% 12/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	10.4% 15/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
General disorders Pain	16.9% 23/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	10.4% 15/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Investigations Weight loss	14.0% 19/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	7.6% 11/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Metabolism and nutrition disorders Anorexia	55.9% 76/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	45.8% 66/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Metabolism and nutrition disorders Dehydration	6.6% 9/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	2.8% 4/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Musculoskeletal and connective tissue disorders Arthralgia	2.2% 3/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	9.0% 13/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Musculoskeletal and connective tissue disorders Arthritis	5.1% 7/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	2.8% 4/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Musculoskeletal and connective tissue disorders Back pain	22.8% 31/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	26.4% 38/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	4.4% 6/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	6.2% 9/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Musculoskeletal and connective tissue disorders Pain in extremity	5.1% 7/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	9.7% 14/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumor pain	7.4% 10/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	10.4% 15/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Nervous system disorders Dizziness	5.9% 8/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	9.0% 13/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Nervous system disorders Dysgeusia	5.9% 8/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	8.3% 12/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Nervous system disorders Headache	11.0% 15/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	12.5% 18/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Nervous system disorders Peripheral sensory neuropathy	31.6% 43/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	26.4% 38/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Psychiatric disorders Anxiety	11.8% 16/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	8.3% 12/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Psychiatric disorders Depression	8.8% 12/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	5.6% 8/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Psychiatric disorders Insomnia	23.5% 32/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	23.6% 34/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Renal and urinary disorders Urinary frequency	5.1% 7/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	3.5% 5/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Renal and urinary disorders Urine discoloration	27.9% 38/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	4.2% 6/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Respiratory, thoracic and mediastinal disorders Cough	25.0% 34/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	21.5% 31/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Respiratory, thoracic and mediastinal disorders Dyspnea	26.5% 36/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	31.2% 45/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Skin and subcutaneous tissue disorders Dry skin	6.6% 9/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	7.6% 11/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Skin and subcutaneous tissue disorders Other skin and subcutaneous tissue disorders	5.9% 8/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	6.2% 9/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysesthesia syndrome	5.9% 8/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	4.9% 7/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Skin and subcutaneous tissue disorders Pruritus	5.1% 7/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	6.2% 9/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Skin and subcutaneous tissue disorders Rash acneiform	5.9% 8/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	4.9% 7/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Vascular disorders Hypertension	19.9% 27/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	16.7% 24/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.
Vascular disorders Thromboembolic event	6.6% 9/136 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.	2.8% 4/144 • 36 months Adverse event and/or serious adverse event were collected only from patients who had received at least one dose of protocol treatment. Two patients who were randomized to BBI608 group did not receive any drug and, thus, were not included in the reporting of adverse events.

Additional Information

Dr. Derek Jonker

The Ottawa Hospital Regional Cancer Centre

Phone: 613-737-7700

Email: djonker@ottawahospital.on.ca

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place