Trial Outcomes & Findings for A Phase 2 Randomized, Open-Label Study of RRx-001 vs Regorafenib in Subjects With Metastatic Colorectal Cancer (NCT NCT02096354)

NCT ID: NCT02096354

Last Updated: 2024-10-15

Results Overview

From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 47 months

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 62 participants
• Primary outcome timeframe: From date of enrollment until death or censorship.
• Results posted on: 2024-10-15

Participant Flow

Participants were recruited based on physician referral at four academic medical centers between May 2014 and October 2019. The first participant first visit was May 22, 2014 and the last patient last visit was October 8, 2020.

62 participants provided informed consent to participate in the study. Prior to arm assignment, 11 patients dropped out. Thus, 51 participants were eligible to be randomized to a study arm with all 51 receiving treatment on protocol. 34 participants were evaluable and included in the efficacy population within the mITT during the interim analysis. All 51 participants are included in the safety analysis.

Participant milestones

Measure	RRx-001 Followed by Irinotecan Once-weekly intravenous RRx-001 at a dose of 4 mg on Days 1, 8, 15, and 22 of a 4-week cycle. On progression and if eligible, patients will receive irinotecan (with or without bevacizumab)	Regorafenib Followed by Irinotecan Regorafenib daily on Days 1- 21 of a 4-week cycle. On progression and if eligible, patients will receive irinotecan (with or without bevacizumab)	Not Randomized Patients that consented to the study but dropped prior to Randomization.
Overall Study STARTED	38	13	11
Overall Study COMPLETED	24	3	0
Overall Study NOT COMPLETED	14	10	11

Reasons for withdrawal

Measure	RRx-001 Followed by Irinotecan Once-weekly intravenous RRx-001 at a dose of 4 mg on Days 1, 8, 15, and 22 of a 4-week cycle. On progression and if eligible, patients will receive irinotecan (with or without bevacizumab)	Regorafenib Followed by Irinotecan Regorafenib daily on Days 1- 21 of a 4-week cycle. On progression and if eligible, patients will receive irinotecan (with or without bevacizumab)	Not Randomized Patients that consented to the study but dropped prior to Randomization.
Overall Study Physician Decision	4	5	0
Overall Study Withdrawal by Subject	3	1	0
Overall Study Adverse Event	7	4	0
Overall Study Ineligible	0	0	11

Baseline Characteristics

Efficacy Data is analyzed on the 34 patients included in the interim analysis. The team extended the study into a safety extension. All 51 subjects are included in the safety analysis

Baseline characteristics by cohort

Measure	RRx-001 Followed by Irinotecan n=38 Participants Once-weekly intravenous RRx-001 at a dose of 4 mg on Days 1, 8, 15, and 22 of a 4-week cycle. On progression and if eligible, patients will receive irinotecan (with or without bevacizumab)	Regorafenib Followed by Irinotecan n=13 Participants Regorafenib daily on Days 1- 21 of a 4-week cycle. On progression and if eligible, patients will receive irinotecan (with or without bevacizumab)	Not Randomized n=11 Participants Patients consented to the trial but dropped out prior due to ineligibility to proceed to randomization	Total n=62 Participants Total of all reporting groups
Age, Continuous	53.7 years STANDARD_DEVIATION 10.41 • n=38 Participants	61.2 years STANDARD_DEVIATION 11.65 • n=13 Participants	58.1 years STANDARD_DEVIATION 10.25 • n=11 Participants	56.4 years STANDARD_DEVIATION 9.33 • n=62 Participants
Sex: Female, Male Female	21 Participants n=38 Participants	9 Participants n=13 Participants	6 Participants n=11 Participants	36 Participants n=62 Participants
Sex: Female, Male Male	17 Participants n=38 Participants	4 Participants n=13 Participants	5 Participants n=11 Participants	26 Participants n=62 Participants
Race/Ethnicity, Customized White	21 Participants n=38 Participants	11 Participants n=13 Participants	10 Participants n=11 Participants	42 Participants n=62 Participants
Race/Ethnicity, Customized Black or African American	5 Participants n=38 Participants	0 Participants n=13 Participants	0 Participants n=11 Participants	5 Participants n=62 Participants
Race/Ethnicity, Customized Unknown	1 Participants n=38 Participants	0 Participants n=13 Participants	1 Participants n=11 Participants	2 Participants n=62 Participants
Race/Ethnicity, Customized Asian	11 Participants n=38 Participants	1 Participants n=13 Participants	0 Participants n=11 Participants	12 Participants n=62 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=38 Participants	1 Participants n=13 Participants	0 Participants n=11 Participants	1 Participants n=62 Participants
Region of Enrollment United States	24 participants n=24 Participants • Efficacy Data is analyzed on the 34 patients included in the interim analysis. The team extended the study into a safety extension. All 51 subjects are included in the safety analysis	10 participants n=10 Participants • Efficacy Data is analyzed on the 34 patients included in the interim analysis. The team extended the study into a safety extension. All 51 subjects are included in the safety analysis	11 participants n=11 Participants • Efficacy Data is analyzed on the 34 patients included in the interim analysis. The team extended the study into a safety extension. All 51 subjects are included in the safety analysis	45 participants n=45 Participants • Efficacy Data is analyzed on the 34 patients included in the interim analysis. The team extended the study into a safety extension. All 51 subjects are included in the safety analysis

PRIMARY outcome

Timeframe: From date of enrollment until death or censorship.

From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 47 months

Outcome measures

Measure	RRx-001 Followed by Irinotecan n=24 Participants Once-weekly intravenous RRx-001 at a dose of 4 mg on Days 1, 8, 15, and 22 of a 4-week cycle. On progression and if eligible, patients will receive irinotecan (with or without bevacizumab)	Regorafenib Followed by Irinotecan n=10 Participants Regorafenib daily on Days 1- 21 of a 4-week cycle. On progression and if eligible, patients will receive irinotecan (with or without bevacizumab)
Overall Survival	8.6 months Interval 4.8 to Based on the Brookmeyer-Crowley CI formula, there is not enough events at the upper limit interval to allow for an estimate, therefore upper limit is NA.	4.7 months Interval 2.2 to Based on the Brookmeyer-Crowley CI formula, there is not enough events at the upper limit interval to allow for an estimate, therefore upper limit is NA.

SECONDARY outcome

Timeframe: Baseline, every 6-8 weeks while on study.

Progression-free survival (PFS) will be defined as the elapsed time from the from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 77 months

Outcome measures

Measure	RRx-001 Followed by Irinotecan n=24 Participants Once-weekly intravenous RRx-001 at a dose of 4 mg on Days 1, 8, 15, and 22 of a 4-week cycle. On progression and if eligible, patients will receive irinotecan (with or without bevacizumab)	Regorafenib Followed by Irinotecan n=10 Participants Regorafenib daily on Days 1- 21 of a 4-week cycle. On progression and if eligible, patients will receive irinotecan (with or without bevacizumab)
Progression Free Survival	6.1 months Interval 3.7 to Based on the Brookmeyer-Crowley CI formula, there is not enough events at the upper limit interval to allow for an estimate, therefore upper limit is NA.	1.7 months Interval 0.7 to Based on the Brookmeyer-Crowley CI formula, there is not enough events at the upper limit interval to allow for an estimate, therefore upper limit is NA.

SECONDARY outcome

Timeframe: Baseline through end of treatment (28 days after last dose of study drug). Approximately 24 weeks.

Incidence of related Adverse Events (AEs). SAEs and all other non-serious AEs are located in the Reported Adverse Event Module. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events.

Outcome measures

Measure	RRx-001 Followed by Irinotecan n=275 Number of Events Once-weekly intravenous RRx-001 at a dose of 4 mg on Days 1, 8, 15, and 22 of a 4-week cycle. On progression and if eligible, patients will receive irinotecan (with or without bevacizumab)	Regorafenib Followed by Irinotecan n=150 Number of Events Regorafenib daily on Days 1- 21 of a 4-week cycle. On progression and if eligible, patients will receive irinotecan (with or without bevacizumab)
Number of Adverse Events CTCAE Grade 1	184 Number of total adverse events	87 Number of total adverse events
Number of Adverse Events CTCAE Grade 2	76 Number of total adverse events	48 Number of total adverse events
Number of Adverse Events CTCAE Grade 3	15 Number of total adverse events	15 Number of total adverse events
Number of Adverse Events CTCAE Grade 4	0 Number of total adverse events	0 Number of total adverse events
Number of Adverse Events CTCAE Grade 5	0 Number of total adverse events	0 Number of total adverse events

SECONDARY outcome

Timeframe: Up to 2 years

Percentage of participants with ORR based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). CR was defined as complete disappearance of all target and non-target disease. PR applied only to participants with at least one measurable lesion. Greater than or equal to 30 % decrease under baseline of the sum of longest diameters of all target measurable lesions.

Outcome measures

Measure	RRx-001 Followed by Irinotecan n=24 Participants Once-weekly intravenous RRx-001 at a dose of 4 mg on Days 1, 8, 15, and 22 of a 4-week cycle. On progression and if eligible, patients will receive irinotecan (with or without bevacizumab)	Regorafenib Followed by Irinotecan n=10 Participants Regorafenib daily on Days 1- 21 of a 4-week cycle. On progression and if eligible, patients will receive irinotecan (with or without bevacizumab)
Objective Response Rate Partial Response	5 Participants	0 Participants
Objective Response Rate Stable Disease	12 Participants	4 Participants
Objective Response Rate Progressive Disease	6 Participants	6 Participants
Objective Response Rate Non-Evaluable	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 2 years

The period from study entry through Disease Control. Disease Control Rate (DCR) also correlates to Clinical Benefit Rate (CBR), defined as the percentage of subjects with CR, PR or SD relative to the total number of treated subjects

Outcome measures

Measure	RRx-001 Followed by Irinotecan n=24 Participants Once-weekly intravenous RRx-001 at a dose of 4 mg on Days 1, 8, 15, and 22 of a 4-week cycle. On progression and if eligible, patients will receive irinotecan (with or without bevacizumab)	Regorafenib Followed by Irinotecan n=10 Participants Regorafenib daily on Days 1- 21 of a 4-week cycle. On progression and if eligible, patients will receive irinotecan (with or without bevacizumab)
Clinical Benefit Rate	17 Participants	4 Participants

Adverse Events

RRx-001 Followed by Irinotecan

Serious events: 14 serious events

Other events: 19 other events

Deaths: 3 deaths

Regorafenib Followed by Irinotecan

Serious events: 7 serious events

Other events: 10 other events

Deaths: 1 deaths

Serious adverse events

Measure	RRx-001 Followed by Irinotecan n=38 participants at risk Once-weekly intravenous RRx-001 at a dose of 4 mg on Days 1, 8, 15, and 22 of a 4-week cycle. On progression and if eligible, patients will receive irinotecan (with or without bevacizumab) RRx-001 Irinotecan: To be dosed after RRx-001 or regorafenib	Regorafenib Followed by Irinotecan n=13 participants at risk Regorafenib daily on Days 1- 21 of a 4-week cycle. On progression and if eligible, patients will receive irinotecan (with or without bevacizumab) Regorafenib Irinotecan: To be dosed after RRx-001 or regorafenib
Blood and lymphatic system disorders Anaemia	2.6% 1/38 • Number of events 1 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	0.00% 0/13 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Blood and lymphatic system disorders Iron deficiency anaemia	2.6% 1/38 • Number of events 1 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	0.00% 0/13 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Cardiac disorders Myocardial infarction	2.6% 1/38 • Number of events 1 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	0.00% 0/13 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Cardiac disorders Tachycardia	2.6% 1/38 • Number of events 1 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	0.00% 0/13 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Congenital, familial and genetic disorders AV Malformations	0.00% 0/38 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	7.7% 1/13 • Number of events 1 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Gastrointestinal disorders Abdominal pain	2.6% 1/38 • Number of events 1 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	7.7% 1/13 • Number of events 1 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Gastrointestinal disorders Abdominal Pain lower	0.00% 0/38 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	7.7% 1/13 • Number of events 1 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Gastrointestinal disorders Constipation	0.00% 0/38 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	7.7% 1/13 • Number of events 1 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Gastrointestinal disorders Enterovesical fistula	2.6% 1/38 • Number of events 1 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	0.00% 0/13 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Gastrointestinal disorders Intestinal obstruction	2.6% 1/38 • Number of events 1 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	0.00% 0/13 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Gastrointestinal disorders Lower Gastrointestinal haemorrhage	0.00% 0/38 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	7.7% 1/13 • Number of events 1 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Gastrointestinal disorders Nausea	2.6% 1/38 • Number of events 1 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	0.00% 0/13 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Gastrointestinal disorders Rectal haemorrhage	5.3% 2/38 • Number of events 3 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	0.00% 0/13 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Gastrointestinal disorders Small intestinal obstruction	5.3% 2/38 • Number of events 2 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	0.00% 0/13 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Gastrointestinal disorders Vomiting	2.6% 1/38 • Number of events 1 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	0.00% 0/13 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
General disorders Disease progression	7.9% 3/38 • Number of events 3 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	0.00% 0/13 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
General disorders Systemic inflammatory response syndrome	2.6% 1/38 • Number of events 1 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	0.00% 0/13 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Hepatobiliary disorders Acute hepatic failure	2.6% 1/38 • Number of events 1 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	0.00% 0/13 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Infections and infestations Bacteraemia	2.6% 1/38 • Number of events 1 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	0.00% 0/13 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Infections and infestations Biliary sepsis	2.6% 1/38 • Number of events 2 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	0.00% 0/13 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Infections and infestations Infection	5.3% 2/38 • Number of events 2 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	0.00% 0/13 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Infections and infestations Influenza	2.6% 1/38 • Number of events 1 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	0.00% 0/13 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Infections and infestations Pneumonia	5.3% 2/38 • Number of events 4 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	0.00% 0/13 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Infections and infestations Urinary tract infection	2.6% 1/38 • Number of events 1 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	0.00% 0/13 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Injury, poisoning and procedural complications Spinal fracture	2.6% 1/38 • Number of events 1 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	0.00% 0/13 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Metabolism and nutrition disorders Dehydration	2.6% 1/38 • Number of events 1 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	0.00% 0/13 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Metabolism and nutrition disorders Hyperglycemia	2.6% 1/38 • Number of events 1 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	0.00% 0/13 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Metabolism and nutrition disorders Hyponatraemia	2.6% 1/38 • Number of events 1 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	0.00% 0/13 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Musculoskeletal and connective tissue disorders Flank pain	0.00% 0/38 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	7.7% 1/13 • Number of events 1 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Nervous system disorders Hepatic encephalopathy	2.6% 1/38 • Number of events 1 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	0.00% 0/13 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Nervous system disorders Hydrocephalus	2.6% 1/38 • Number of events 1 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	0.00% 0/13 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Psychiatric disorders Delirium	2.6% 1/38 • Number of events 1 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	0.00% 0/13 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Psychiatric disorders Mental status changes	2.6% 1/38 • Number of events 1 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	7.7% 1/13 • Number of events 1 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Renal and urinary disorders Acute kidney injury	2.6% 1/38 • Number of events 1 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	0.00% 0/13 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Renal and urinary disorders Acute Renal Failure	2.6% 1/38 • Number of events 1 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	0.00% 0/13 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Renal and urinary disorders Hydronephrosis	0.00% 0/38 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	7.7% 1/13 • Number of events 1 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Respiratory, thoracic and mediastinal disorders Bronchial Obstruction	2.6% 1/38 • Number of events 1 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	0.00% 0/13 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.6% 1/38 • Number of events 2 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	0.00% 0/13 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/38 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	7.7% 1/13 • Number of events 1 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Respiratory, thoracic and mediastinal disorders Pleural effusion	5.3% 2/38 • Number of events 2 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	0.00% 0/13 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Skin and subcutaneous tissue disorders Drug Eruption	0.00% 0/38 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	7.7% 1/13 • Number of events 1 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.

Other adverse events

Measure	RRx-001 Followed by Irinotecan n=38 participants at risk Once-weekly intravenous RRx-001 at a dose of 4 mg on Days 1, 8, 15, and 22 of a 4-week cycle. On progression and if eligible, patients will receive irinotecan (with or without bevacizumab) RRx-001 Irinotecan: To be dosed after RRx-001 or regorafenib	Regorafenib Followed by Irinotecan n=13 participants at risk Regorafenib daily on Days 1- 21 of a 4-week cycle. On progression and if eligible, patients will receive irinotecan (with or without bevacizumab) Regorafenib Irinotecan: To be dosed after RRx-001 or regorafenib
Gastrointestinal disorders Abdominal pain	23.7% 9/38 • Number of events 10 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	46.2% 6/13 • Number of events 7 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Gastrointestinal disorders Enterovesical fistula	5.3% 2/38 • Number of events 8 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	0.00% 0/13 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Gastrointestinal disorders Intestinal obstruction	0.00% 0/38 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	7.7% 1/13 • Number of events 1 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Gastrointestinal disorders Small intestinal obstruction	10.5% 4/38 • Number of events 17 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	0.00% 0/13 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Gastrointestinal disorders Stomatitis	0.00% 0/38 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	7.7% 1/13 • Number of events 1 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
General disorders Disease progression	18.4% 7/38 • Number of events 47 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	15.4% 2/13 • Number of events 2 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
General disorders Fatigue	42.1% 16/38 • Number of events 22 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	53.8% 7/13 • Number of events 8 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Hepatobiliary disorders Hyperbilirubinaemia	0.00% 0/38 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	30.8% 4/13 • Number of events 4 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Infections and infestations Urinary tract infection	15.8% 6/38 • Number of events 11 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	15.4% 2/13 • Number of events 6 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Injury, poisoning and procedural complications Infusion related reaction	34.2% 13/38 • Number of events 182 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	0.00% 0/13 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Injury, poisoning and procedural complications Spinal fracture	2.6% 1/38 • Number of events 3 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	7.7% 1/13 • Number of events 1 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Investigations Alanine aminotransferase increased	0.00% 0/38 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	15.4% 2/13 • Number of events 4 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Investigations Aspartate aminotransferase increased	0.00% 0/38 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	30.8% 4/13 • Number of events 7 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Investigations Blood alkaline phosphatase increased	0.00% 0/38 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	15.4% 2/13 • Number of events 2 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Investigations Blood bilirubin increased	0.00% 0/38 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	23.1% 3/13 • Number of events 6 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Investigations Liver function test abnormal	5.3% 2/38 • Number of events 8 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	0.00% 0/13 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Metabolism and nutrition disorders Hypokalaemia	10.5% 4/38 • Number of events 6 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	7.7% 1/13 • Number of events 1 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Metabolism and nutrition disorders Hyponatraemia	10.5% 4/38 • Number of events 5 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	7.7% 1/13 • Number of events 1 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Musculoskeletal and connective tissue disorders Arthralgia	2.6% 1/38 • Number of events 1 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	7.7% 1/13 • Number of events 2 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Musculoskeletal and connective tissue disorders Back Pain	18.4% 7/38 • Number of events 9 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	30.8% 4/13 • Number of events 4 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Musculoskeletal and connective tissue disorders Groin Pain	0.00% 0/38 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	7.7% 1/13 • Number of events 1 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Musculoskeletal and connective tissue disorders Pain in Extremity	0.00% 0/38 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	61.5% 8/13 • Number of events 15 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant pleural effusion	5.3% 2/38 • Number of events 6 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	0.00% 0/13 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to liver	10.5% 4/38 • Number of events 10 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	0.00% 0/13 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pseudoprogression	7.9% 3/38 • Number of events 10 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	0.00% 0/13 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Nervous system disorders Ataxia	0.00% 0/38 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	7.7% 1/13 • Number of events 1 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Psychiatric disorders Anxiety	10.5% 4/38 • Number of events 5 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	7.7% 1/13 • Number of events 1 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Psychiatric disorders Depression	5.3% 2/38 • Number of events 2 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	0.00% 0/13 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Psychiatric disorders Insomnia	15.8% 6/38 • Number of events 7 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	7.7% 1/13 • Number of events 1 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Respiratory, thoracic and mediastinal disorders Dyspnoea	7.9% 3/38 • Number of events 5 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	15.4% 2/13 • Number of events 2 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Skin and subcutaneous tissue disorders Night sweats	5.3% 2/38 • Number of events 3 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	15.4% 2/13 • Number of events 2 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaethesia syndrome	0.00% 0/38 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	30.8% 4/13 • Number of events 9 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/38 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	53.8% 7/13 • Number of events 7 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Vascular disorders Hypertension	15.8% 6/38 • Number of events 9 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	30.8% 4/13 • Number of events 8 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Blood and lymphatic system disorders Anemia	7.9% 3/38 • Number of events 6 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	15.4% 2/13 • Number of events 2 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Blood and lymphatic system disorders Hypercoagulability	5.3% 2/38 • Number of events 4 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	0.00% 0/13 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Cardiac disorders Tachycardia	13.2% 5/38 • Number of events 6 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	7.7% 1/13 • Number of events 1 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Gastrointestinal disorders Ascites	5.3% 2/38 • Number of events 16 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	7.7% 1/13 • Number of events 1 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Gastrointestinal disorders Constipation	15.8% 6/38 • Number of events 14 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	7.7% 1/13 • Number of events 1 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Gastrointestinal disorders Diarrhea	31.6% 12/38 • Number of events 13 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	7.7% 1/13 • Number of events 1 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Gastrointestinal disorders Vomiting	23.7% 9/38 • Number of events 14 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	15.4% 2/13 • Number of events 3 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Gastrointestinal disorders Mucositis oral	0.00% 0/38 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	30.8% 4/13 • Number of events 14 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Metabolism and nutrition disorders Anorexia	0.00% 0/38 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	69.2% 9/13 • Number of events 9 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Nervous system disorders Headache	0.00% 0/38 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	46.2% 6/13 • Number of events 7 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.
Skin and subcutaneous tissue disorders Erythema	0.00% 0/38 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.	61.5% 8/13 • Number of events 12 • Serious Adverse Events and **Other (Not Including Serious) Adverse Events** were collected beginning at baseline through end of treatment (28 days after last dose of study drug). All-Cause Mortality was assessed up to 47 months" National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 is used to grade adverse events. Other Adverse Events are reported at 0% or higher for related to study drug RRx-001.

Additional Information

Study Director: Bryan Oronsky, Chief Medical Officer

EpicentRx, Inc

Phone: 858-229-1062

Email: boronsky@epicentrx.com

Results disclosure agreements

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