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

• Sponsor: NCIC Clinical Trials Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT01830621
• Collaborator: Sumitomo Pharma Oncology, Inc. (Industry)
• Enrollment: 282
• Locations: 63
• Arms: 2
• Actual Duration (Months): 37
• Patients Per Site: 4.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to find out whether it is better to receive a new drug, BBI608, or better to receive no further treatment for colon or rectal cancer. To do this, half of the patients in this study will get BBI608 and the other half will receive a placebo (a substance that is designed not to do anything).

Condition or Disease	Intervention/Treatment	Phase
Colorectal Carcinoma	Drug: BBI608; Drug: Placebo; Other: Best Supportive Care	Phase 3

Detailed Description

This research is being done because currently there are no approved remaining effective treatments for colon or rectal cancer.

The purpose of this study is to compare the effects on colon cancer of a new drug, BBI608, and best supportive care (BSC) compared to BSC alone.

BBI608 has been shown to shrink tumours in animals and has been studied in a few people and seems promising, but it is not clear if it can offer better results than the usual care which is best supportive care alone.

The standard or usual treatment for this disease is treatment with drugs and other treatments that may help to make a patient feel better or may improve their quality of life. This treatment is known as "best supportive care" (BSC). Although patients with best supportive care can feel better for some months, the cancer usually continues to grow.

Study Design

• Study Type: Interventional
• Actual Enrollment: 282 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase III Randomized Study of BBI608 and Best Supportive Care Versus Placebo and Best Supportive Care in Patients With Pretreated Advanced Colorectal Carcinoma
• Actual Study Start Date: Apr 15, 2013
• Actual Primary Completion Date: Dec 21, 2015
• Actual Study Completion Date: May 16, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: BBI608 BBI608 480 mg two times daily (960 mg total daily dose)+ Best Supportive Care	Drug: BBI608; Other: Best Supportive Care
Placebo Comparator: Placebo Placebo two times daily + Best Supportive Care	Drug: Placebo; Other: Best Supportive Care

Outcome Measures

Primary Outcome Measures

1. Overall Survival [38 month]

   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).

Secondary Outcome Measures

1. Progression Free Survival [38 months]

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

2. Disease Control Rate [38 months]

   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.

3. Number of Patients With Adverse Events [38 months]

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

4. Change of Global Quality of Life at 8 Weeks From Baseline [8 weeks]

   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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically confirmed advanced colorectal cancer that is unresectable.

• Received a prior thymidylate synthase inhibitor (e.g. 5-fluorouracil (5-FU), capecitabine, raltitrexed, UFT) for metastatic disease or as adjuvant therapy.

• Received and failed an irinotecan containing regimen (i.e. single-agent or in combination) for treatment of metastatic disease, OR relapsed within 6 months of completion of an irinotecan-containing adjuvant therapy, OR have documented unsuitability for an irinotecan-containing regimen.

• Received and failed an oxaliplatin-containing regimen for treatment of metastatic disease, OR relapsed within 6 months of completion of an oxaliplatin-containing adjuvant therapy OR have documented unsuitability for an oxaliplatin-containing regimen.

• For patients with colorectal cancer that is K-ras wild type: Received and failed a cetuximab or panitumumab-containing regimen (i.e. single-agent or in combination) for treatment of metastatic disease OR have documented unsuitability for a cetuximab or panitumumab-containing regimen

• The only remaining standard available therapy as recommended by the Investigator is best supportive care.

• Must have presence of measurable disease as defined by Response Evaluation Criteria in Solid Tumours (RECIST 1.1).

• Imaging investigations including CT/MRI of chest/abdomen/pelvis or other scans as necessary to document all sites of disease done within 14 days prior to randomization.

• Must have an ECOG Performance Status of 0 or 1.

• Must be ≥ 18 years of age.

• For male or female patient of child producing potential: Must agree to use contraception or take measures to avoid pregnancy during the study and for 30 days after the last Protocol treatment dose.

• Women of child bearing potential (WOCBP) must have a negative serum or urine pregnancy test within 72 hours prior to randomization.

• Must have alanine transaminase (ALT) ≤ 3 × institutional upper limit of normal (ULN) [≤ 5 × ULN in presence of liver metastases] within 14 days prior to randomization.

• Must have hemoglobin (Hgb) ≥ 80 g/L within 14 days prior to randomization.

• Must have total bilirubin ≤ 1.5 × institutional ULN [≤ 2.0 x ULN in presence of liver metastases] within 14 days prior to randomization.

• Must have creatinine ≤ 1.5 × institutional ULN or Creatinine Clearance > 50 ml/min within 14 days prior to randomization.

• Must have absolute neutrophil count ≥ 1.5 x 109/L within 14 days prior to randomization.

• Must have platelet count ≥ 75 x 109/L within 14 days prior to randomization.

• Other biochemistry which must be done within 14 days prior to randomization includes lactate dehydrogenase (LDH) and alkaline phosphatase.

• Patient must consent to provision of, and investigator(s) must confirm access to and agree to submit at the request of the NCIC CTG Central Tumour Bank, a representative formalin fixed paraffin block of tumour tissue in order that the specific correlative marker assays may be conducted.

• Patient must consent to provision of a sample of blood in order that the specific correlative marker assays may be conducted.

• Patient is able (i.e. sufficiently fluent) and willing to complete the Quality of Life and Health Utilities questionnaires in one of the validated languages for the questionnaires.

• Patients must be accessible for treatment and follow-up. Patients registered on this trial must be treated and followed at the participating centre. This implies there must be reasonable geographical limits placed on patients being considered for this trial.

• Protocol treatment is to begin within 2 working days of patient randomization.

• The patient is not receiving therapy in a concurrent clinical study and the patient agrees not to participate in other clinical studies during their participation in this trial while on study treatment.

Exclusion Criteria:

• Anti-cancer chemotherapy or biologic therapy within the lesser of i) 21 days, or ii) the usual cycle length of the regimen (e.g. 14 days for FOLFOX), prior to the first planned dose of BBI608/placebo. An exception is made for capecitabine and regorafenib, where a minimum of 10 days since last dose must be observed prior to the first planned dose of BBI608/placebo.

• Radiotherapy, immunotherapy, or investigational agents within four weeks of first planned dose of BBI608/placebo, with the exception of a single dose of radiation up to 8 Gray (equal to 800 RAD) with palliative intent for pain control up to 14 days before randomization.

• Major surgery within 4 weeks prior to randomization.

• Any known symptomatic brain metastases requiring steroids.

• Women who are pregnant or breastfeeding.

• Gastrointestinal disorder(s) which, in the opinion of the Qualified/Principal Investigator, would significantly impede the absorption of an oral agent (e.g. active Crohn's disease, ulcerative colitis, extensive gastric and small intestine resection).

• Unable or unwilling to swallow BBI608/placebo capsules daily.

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, clinically significant non-healing or healing wounds, symptomatic congestive heart failure, unstable angina pectoris, clinically significant cardiac arrhythmia, significant pulmonary disease (shortness of breath at rest or mild exertion), uncontrolled infection or psychiatric illness/social situations that would limit compliance with study requirements.

• Patients with a history of other malignancies except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for ≥ 5 years.

• Prior treatment with BBI608.

• Any active disease condition which would render the protocol treatment dangerous or impair the ability of the patient to receive protocol therapy.

• Any condition (e.g. psychological, geographical, etc.) that does not permit compliance with the protocol.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Bankstown/ Lidcombe	Bankstown	New South Wales	Australia	2200
2	Townsville Hospital	Douglas	Queensland	Australia	4814
3	Flinders Medical Centre	Bedford Park	South Australia	Australia	5042
4	Lyell McEwin Hospital	Elizabeth Vale	South Australia	Australia	5112
5	The Queen Elizabeth Hospital	Woodville South	South Australia	Australia	5011
6	Royal Hobart Hospital	Hobart	Tasmania	Australia	7000
7	Peter MacCallum Cancer Institute	East Melbourne	Victoria	Australia	3002
8	St John of God - Subiaco	Subiaco	Western Australia	Australia	6008
9	St John of God Bunbury Hospital	Bunbury		Australia	6230
10	Tom Baker Cancer Centre	Calgary	Alberta	Canada	T2N 4N2
11	Cross Cancer Institute	Edmonton	Alberta	Canada	T6G 1Z2
12	BCCA - Abbotsford Centre	Abbotsford	British Columbia	Canada	V2S 0C2
13	BCCA - Cancer Centre for the Southern Interior	Kelowna	British Columbia	Canada	V1Y 5L3
14	BCCA - Fraser Valley Cancer Centre	Surrey	British Columbia	Canada	V3V 1Z2
15	BCCA - Vancouver Cancer Centre	Vancouver	British Columbia	Canada	V5Z 4E6
16	BCCA - Vancouver Island Cancer Centre	Victoria	British Columbia	Canada	V8R 6V5
17	CancerCare Manitoba	Winnipeg	Manitoba	Canada	R3E 0V9
18	Horizon Health Network,	Fredericton	New Brunswick	Canada	E3B 5N5
19	The Moncton Hospital	Moncton	New Brunswick	Canada	E1C 6Z8
20	The Vitalite Health Network - Dr. Leon Richard	Moncton	New Brunswick	Canada	E1C 8X3
21	Atlantic Health Sciences Corporation	Saint John	New Brunswick	Canada	E2L 4L2
22	Dr. H. Bliss Murphy Cancer Centre	St. John's	Newfoundland and Labrador	Canada	A1B 3V6
23	QEII Health Sciences Centre	Halifax	Nova Scotia	Canada	B3H 1V7
24	The Royal Victoria Hospital	Barrie	Ontario	Canada	L4M 6M2
25	Juravinski Cancer Centre at Hamilton Health Sciences	Hamilton	Ontario	Canada	L8V 5C2
26	London Regional Cancer Program	London	Ontario	Canada	N6A 4L6
27	Credit Valley Hospital	Mississauga	Ontario	Canada	L5M 2N1
28	Lakeridge Health Oshawa	Oshawa	Ontario	Canada	L1G 2B9
29	Ottawa Hospital Research Institute	Ottawa	Ontario	Canada	K1H 8L6
30	Algoma District Cancer Program	Sault Ste. Marie	Ontario	Canada	P6B 0A8
31	Niagara Health System	St. Catharines	Ontario	Canada	L2S 0A9
32	Health Sciences North	Sudbury	Ontario	Canada	P3E 5J1
33	Thunder Bay Regional Health Science Centre	Thunder Bay	Ontario	Canada	P7B 6V4
34	Toronto East General Hospital	Toronto	Ontario	Canada	M4C 3E7
35	Odette Cancer Centre	Toronto	Ontario	Canada	M4N 3M5
36	St. Michael's Hospital	Toronto	Ontario	Canada	M5B 1W8
37	Mount Sinai Hospital	Toronto	Ontario	Canada	M5G 1X5
38	Univ. Health Network-Princess Margaret Hospital	Toronto	Ontario	Canada	M5G 2M9
39	Hopital de la Cite-de-la-Sante	Laval	Quebec	Canada	H7M 3L9
40	L'Hotel-Dieu de Levis	Levis	Quebec	Canada	G6V 3Z1
41	CHUM - Hopital Notre-Dame	Montreal	Quebec	Canada	H2L 4M1
42	McGill University - Dept. Oncology	Montreal	Quebec	Canada	H2W 1S6
43	CHUQ-Pavillon Hotel-Dieu de Quebec	Quebec City	Quebec	Canada	G1R 2J6
44	CHA-Hopital Du St-Sacrement	Quebec City	Quebec	Canada	G1S 4L8
45	Centre hospitalier universitaire de Sherbrooke	Sherbrooke	Quebec	Canada	J1H 5N4
46	Centre hospitalier regional de Trois-Rivieres	Trois-Rivieres	Quebec	Canada	G8Z 3R9
47	Allan Blair Cancer Centre	Regina	Saskatchewan	Canada	S4T 7T1
48	Saskatoon Cancer Centre	Saskatoon	Saskatchewan	Canada	S7N 4H4
49	Chiba Cancer Center	Chiba		Japan
50	National Kyushu Cancer Center	Fukuoka		Japan
51	National Cancer Center Hospital East	Kashiwa		Japan
52	Kobe City Medical Center General Hospital	Kobe		Japan
53	National Hospital Organization Shikoku Cancer Center	Matsuyama		Japan
54	Kyorin University Hospital	Mitaka		Japan
55	Aichi Cancer Center Hospital	Nagoya		Japan
56	Osaka Medical Center for Cancer and Cardiovascular Diseases	Osaka		Japan
57	Saitama Prefectural Cancer Center	Saitama		Japan
58	Hokkaido University Hospital	Sapporo		Japan
59	Shizuoka Cancer Center	Shizuoka		Japan
60	Osaka Medical College Hospital	Takatsuki		Japan
61	Cancer Institute Hospital of JFCR	Tokyo		Japan
62	Keio University Hospital	Tokyo		Japan
63	National Cancer Center Hospital	Tokyo		Japan

Sponsors and Collaborators

• NCIC Clinical Trials Group
• Sumitomo Pharma Oncology, Inc.

Investigators

• Study Chair: Derek Jonker, Ottawa Health Research Institute - General Division

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: NCIC Clinical Trials Group
• ClinicalTrials.gov Identifier: NCT01830621
• Other Study ID Numbers: CO23
• First Posted: Apr 12, 2013
• Last Update Posted: Apr 14, 2020
• Last Verified: Apr 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Carcinoma; Colorectal Neoplasms

Study Results

Participant Flow

Arm/Group Title	BBI608	Placebo
Arm/Group Description	BBI608 480 mg two times daily (960 mg total daily dose)+ Best Supportive Care BBI608 Best Supportive Care	Placebo two times daily + Best Supportive Care Placebo Best Supportive Care
Period Title: Overall Study
STARTED	138	144
COMPLETED	138	144
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	BBI608	Placebo	Total
Arm/Group Description	BBI608 480 mg two times daily (960 mg total daily dose)+ Best Supportive Care BBI608 Best Supportive Care	Placebo two times daily + Best Supportive Care Placebo Best Supportive Care	Total of all reporting groups
Overall Participants	138	144	282
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	64	64	64
Sex: Female, Male (Count of Participants)
Female	47 34.1%	51 35.4%	98 34.8%
Male	91 65.9%	93 64.6%	184 65.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	1 0.7%	1 0.4%
Asian	26 18.8%	34 23.6%	60 21.3%
Native Hawaiian or Other Pacific Islander	0 0%	1 0.7%	1 0.4%
Black or African American	0 0%	1 0.7%	1 0.4%
White	112 81.2%	107 74.3%	219 77.7%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Canada	64 46.4%	77 53.5%	141 50%
Japan	22 15.9%	22 15.3%	44 15.6%
Australia	52 37.7%	45 31.3%	97 34.4%
ECOG (Eastern Cooperative Oncology Group) Performance Status (Count of Participants)
0	37 26.8%	42 29.2%	79 28%
1	101 73.2%	102 70.8%	203 72%

Outcome Measures

1. Primary Outcome

Title	Overall Survival
Description	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).
Time Frame	38 month

Outcome Measure Data

Analysis Population Description

All patients who were randomized to this study.

Arm/Group Title	BBI608	Placebo
Arm/Group Description	BBI608 480 mg two times daily (960 mg total daily dose)+ Best Supportive Care BBI608 Best Supportive Care	Placebo two times daily + Best Supportive Care Placebo Best Supportive Care
Measure Participants	138	144
Median (95% Confidence Interval) [Months]	4.44	4.76

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BBI608, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.337
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.13
	Confidence Interval	(2-Sided) 95%; 0.88 to 1.46
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Progression Free Survival
Description	Defined as the time from randomization to the first objective documentation of disease progression or death due to any cause.
Time Frame	38 months

Outcome Measure Data

Analysis Population Description

All patients randomized to this study

Arm/Group Title	BBI608	Placebo
Arm/Group Description	BBI608 480 mg two times daily (960 mg total daily dose)+ Best Supportive Care BBI608 Best Supportive Care	Placebo two times daily + Best Supportive Care Placebo Best Supportive Care
Measure Participants	138	144
Median (95% Confidence Interval) [Months]	1.82	1.82

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BBI608, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.837
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.97
	Confidence Interval	(2-Sided) 95%; 0.76 to 1.26
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Disease Control Rate
Description	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.
Time Frame	38 months

Outcome Measure Data

Analysis Population Description

All patients randomized to this study

Arm/Group Title	BBI608	Placebo
Arm/Group Description	BBI608 480 mg two times daily (960 mg total daily dose)+ Best Supportive Care BBI608 Best Supportive Care	Placebo two times daily + Best Supportive Care Placebo Best Supportive Care
Measure Participants	138	144
Count of Participants [Participants]	17 12.3%	18 12.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BBI608, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.955
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.98
	Confidence Interval	(2-Sided) 95%; 0.48 to 2.00
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Number of Patients With Adverse Events
Description	Number of patients with at least one adverse event as assessed by NCI CTCAE Version 3.0 criteria.
Time Frame	38 months

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	BBI608	Placebo
Arm/Group Description	BBI608 480 mg two times daily (960 mg total daily dose)+ Best Supportive Care BBI608 Best Supportive Care	Placebo two times daily + Best Supportive Care Placebo Best Supportive Care
Measure Participants	136	144
Count of Participants [Participants]	135 97.8%	139 96.5%

5. Secondary Outcome

Title	Change of Global Quality of Life at 8 Weeks From Baseline
Description	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).
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	BBI608	Placebo
Arm/Group Description	BBI608 480 mg two times daily (960 mg total daily dose)+ Best Supportive Care BBI608 Best Supportive Care	Placebo two times daily + Best Supportive Care Placebo Best Supportive Care
Measure Participants	55	61
Mean (Standard Deviation) [units on a scale]	-10.61 (23.1)	-10.66 (17.07)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	BBI608, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.72
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Adverse Events

Time Frame	38 months
Adverse Event Reporting Description	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.
Arm/Group Title	BBI608		Placebo
Arm/Group Description	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 two times daily + Best Supportive Care Placebo Best Supportive Care At risk patients included only patients who received at least one dose of placebo
All Cause Mortality
	BBI608		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	127/136 (93.4%)		130/144 (90.3%)
Serious Adverse Events
	BBI608		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	40/136 (29.4%)		29/144 (20.1%)
Blood and lymphatic system disorders
Anemia	1/136 (0.7%)		1/144 (0.7%)
Cardiac disorders
Atrial fibrillation	0/136 (0%)		1/144 (0.7%)
Chest pain - cardiac	1/136 (0.7%)		1/144 (0.7%)
Sinus tachycardia	1/136 (0.7%)		0/144 (0%)
Supraventricular tachycardia	1/136 (0.7%)		0/144 (0%)
Gastrointestinal disorders
Abdominal pain	5/136 (3.7%)		0/144 (0%)
Bloating	0/136 (0%)		3/144 (2.1%)
Colitis	0/136 (0%)		1/144 (0.7%)
Colonic obstruction	1/136 (0.7%)		1/144 (0.7%)
Constipation	1/136 (0.7%)		0/144 (0%)
Diarrhea	6/136 (4.4%)		1/144 (0.7%)
Ileal obstruction	0/136 (0%)		0/144 (0%)
Ileus	0/136 (0%)		1/144 (0.7%)
Jejunal obstruction	1/136 (0.7%)		2/144 (1.4%)
Lower gastrointestinal hemorrhage	1/136 (0.7%)		0/144 (0%)
Nausea	1/136 (0.7%)		0/144 (0%)
Pancreatitis	1/136 (0.7%)		2/144 (1.4%)
Small intestinal obstruction	2/136 (1.5%)		0/144 (0%)
Upper gastrointestinal hemorrhage	1/136 (0.7%)		3/144 (2.1%)
Vomiting	2/136 (1.5%)		0/144 (0%)
General disorders
Edema limbs	0/136 (0%)		2/144 (1.4%)
Edema trunk	0/136 (0%)		1/144 (0.7%)
Fatigue	2/136 (1.5%)		1/144 (0.7%)
Fever	0/136 (0%)		1/144 (0.7%)
Malaise	1/136 (0.7%)		2/144 (1.4%)
Non-cardiac chest pain	1/136 (0.7%)		0/144 (0%)
Hepatobiliary disorders
Other hepatobiliary disorders	1/136 (0.7%)		1/144 (0.7%)
Infections and infestations
Biliary tract infection	3/136 (2.2%)		1/144 (0.7%)
Kidney infection	1/136 (0.7%)		1/144 (0.7%)
Lung infection	1/136 (0.7%)		0/144 (0%)
Other infections and infestations	2/136 (1.5%)		0/144 (0%)
Sepsis	1/136 (0.7%)		0/144 (0%)
Skin infection	0/136 (0%)		2/144 (1.4%)
Upper respiratory infection	0/136 (0%)		1/144 (0.7%)
Urinary tract infection	1/136 (0.7%)		1/144 (0.7%)
Injury, poisoning and procedural complications
Fall	1/136 (0.7%)		1/144 (0.7%)
Intestinal stoma obstruction	1/136 (0.7%)		1/144 (0.7%)
Investigations
Blood bilirubin increased	1/136 (0.7%)		0/144 (0%)
Weight loss	0/136 (0%)		1/144 (0.7%)
Metabolism and nutrition disorders
Anorexia	2/136 (1.5%)		1/144 (0.7%)
Dehydration	7/136 (5.1%)		1/144 (0.7%)
Hyperkalemia	1/136 (0.7%)		2/144 (1.4%)
Musculoskeletal and connective tissue disorders
Back pain	1/136 (0.7%)		0/144 (0%)
Muscle weakness lower limb	1/136 (0.7%)		0/144 (0%)
Nervous system disorders
Dizziness	1/136 (0.7%)		0/144 (0%)
Psychiatric disorders
Confusion	2/136 (1.5%)		0/144 (0%)
Renal and urinary disorders
Acute kidney injury	2/136 (1.5%)		0/144 (0%)
Other renal and urinary disorders	1/136 (0.7%)		1/144 (0.7%)
Reproductive system and breast disorders
Pelvic pain	1/136 (0.7%)		0/144 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/136 (0.7%)		0/144 (0%)
Pleural effusion	0/136 (0%)		1/144 (0.7%)
Pneumonitis	1/136 (0.7%)		2/144 (1.4%)
Tracheal stenosis	1/136 (0.7%)		0/144 (0%)
Vascular disorders
Hypotension	1/136 (0.7%)		0/144 (0%)
Thromboembolic event	1/136 (0.7%)		0/144 (0%)
Other (Not Including Serious) Adverse Events
	BBI608		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	134/136 (98.5%)		137/144 (95.1%)
Gastrointestinal disorders
Abdominal pain	64/136 (47.1%)		56/144 (38.9%)
Bloating	8/136 (5.9%)		9/144 (6.3%)
Constipation	48/136 (35.3%)		60/144 (41.7%)
Diarrhea	117/136 (86%)		46/144 (31.9%)
Dry mouth	11/136 (8.1%)		7/144 (4.9%)
Dyspepsia	8/136 (5.9%)		17/144 (11.8%)
Gastroesophageal reflux disease	10/136 (7.4%)		12/144 (8.3%)
Nausea	85/136 (62.5%)		67/144 (46.5%)
Other gastrointestinal disorders	5/136 (3.7%)		11/144 (7.6%)
Vomiting	60/136 (44.1%)		50/144 (34.7%)
General disorders
Edema limbs	20/136 (14.7%)		29/144 (20.1%)
Fatigue	92/136 (67.6%)		94/144 (65.3%)
Fever	12/136 (8.8%)		15/144 (10.4%)
Pain	23/136 (16.9%)		15/144 (10.4%)
Investigations
Weight loss	19/136 (14%)		11/144 (7.6%)
Metabolism and nutrition disorders
Anorexia	76/136 (55.9%)		66/144 (45.8%)
Dehydration	9/136 (6.6%)		4/144 (2.8%)
Musculoskeletal and connective tissue disorders
Arthralgia	3/136 (2.2%)		13/144 (9%)
Arthritis	7/136 (5.1%)		4/144 (2.8%)
Back pain	31/136 (22.8%)		38/144 (26.4%)
Generalized muscle weakness	6/136 (4.4%)		9/144 (6.3%)
Pain in extremity	7/136 (5.1%)		14/144 (9.7%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor pain	10/136 (7.4%)		15/144 (10.4%)
Nervous system disorders
Dizziness	8/136 (5.9%)		13/144 (9%)
Dysgeusia	8/136 (5.9%)		12/144 (8.3%)
Headache	15/136 (11%)		18/144 (12.5%)
Peripheral sensory neuropathy	43/136 (31.6%)		38/144 (26.4%)
Psychiatric disorders
Anxiety	16/136 (11.8%)		12/144 (8.3%)
Depression	12/136 (8.8%)		8/144 (5.6%)
Insomnia	32/136 (23.5%)		34/144 (23.6%)
Renal and urinary disorders
Urinary frequency	7/136 (5.1%)		5/144 (3.5%)
Urine discoloration	38/136 (27.9%)		6/144 (4.2%)
Respiratory, thoracic and mediastinal disorders
Cough	34/136 (25%)		31/144 (21.5%)
Dyspnea	36/136 (26.5%)		45/144 (31.3%)
Skin and subcutaneous tissue disorders
Dry skin	9/136 (6.6%)		11/144 (7.6%)
Other skin and subcutaneous tissue disorders	8/136 (5.9%)		9/144 (6.3%)
Palmar-plantar erythrodysesthesia syndrome	8/136 (5.9%)		7/144 (4.9%)
Pruritus	7/136 (5.1%)		9/144 (6.3%)
Rash acneiform	8/136 (5.9%)		7/144 (4.9%)
Vascular disorders
Hypertension	27/136 (19.9%)		24/144 (16.7%)
Thromboembolic event	9/136 (6.6%)		4/144 (2.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.