Phase I/II Study of SGI-110 With Irinotecan Versus Regorafenib or TAS-102 in Metastatic Colorectal Cancer

• ClinicalTrials.gov Identifier: NCT01896856
• Recruitment Status: Completed
• First Posted: July 11, 2013
• Results First Posted: September 14, 2020
• Last Update Posted: October 6, 2020
• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborators: Van Andel Research Institute; Astex Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Previously Treated Metastatic Colorectal Cancer
• Interventions: Drug: SGI-110 Dose Escalation; Drug: Regorafenib; Drug: TAS-102; Drug: SGI-110; Drug: Irinotecan
• Enrollment: 118

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Phase 1: Dose Level 1	Phase 1: Dose Level -1	Phase 1: Dose Level -1G	Phase 1: Dose Level 1G	Phase 2: Arm A SGI-110 + Irinotecan	Phase 2: Arm B Regorafenib or TAS-102
Arm/Group Description	Guadecitabine (SGI-110) 45 mg/m^2 was administered as a subcutaneous injection on days 1-5 of each 28-day cycle. Irinotecan 125 mg/m^2 was administered IV on days 8 and 15 of each 28-day cycle.	Guadecitabine (SGI-110) 30 mg/m^2 was administered as a subcutaneous injection on days 1-5 of each 28-day cycle. Irinotecan 125 mg/m^2 was administered IV on days 8 and 15 of each 28-day cycle.	Guadecitabine (SGI-110) 30 mg/m^2 was administered as a subcutaneous injection on days 1-5 of each 28-day cycle. Irinotecan 125 mg/m^2 was administered IV on days 8 and 15 of each 28-day cycle. Growth factor support (filgrastim and peg-filgrastim) mandatory during cycle 1, and given per clinician judgement cycle 2 and beyond.	Guadecitabine (SGI-110) 45 mg/m^2 was administered as a subcutaneous injection on days 1-5 of each 28-day cycle. Irinotecan 125 mg/m^2 was administered IV on days 8 and 15 of each 28-day cycle. Growth factor support (filgrastim and peg-filgrastim) mandatory during cycle 1, and given per clinician judgement cycle 2 and beyond.	SGI-110 45 mg/m^2 was administered as a subcutaneous injection on days 1-5 of each 28-day cycle. Irinotecan 125 mg/m^2 was administered IV on days 8 and 15 of each 28-day cycle. Growth factor support (filgrastim and peg-filgrastim) was given during cycle 1 with option to give additional growth factor support at subsequent cycles per clinician judgement.	Subjects received either regorafenib or Lonsurf (TAS-102). Regorafenib 160 mg was taken orally daily from days 1-21 of each 28-day cycle or TAS-102 35 mg/m^2 was taken orally twice daily on days 1-5 and 8-12 of each 28-day cycle. Subjects that had previously received one of these standard of care drugs (regorafenib or TAS-102) received the other on study. For subjects that had never received either regorafenib or TAS-102, the choice of therapy was deferred to the treating physician and patient.
Period Title: Overall Study
Started	6	3	7	6	62	34
Completed	6	3	6	6	62	34
Not Completed	0	0	1	0	0	0
Reason Not Completed
Transportation issues / Non-compliance	0	0	1	0	0	0

Baseline Characteristics

Arm/Group Title		Phase 1: Dose Level 1	Phase 1: Dose Level -1	Phase 1: Dose Level -1G	Phase 1: Dose Level 1G	Phase 2: Arm A SGI-110 + Irinotecan	Phase 2: Arm B Regorafenib or TAS-102	Total
Arm/Group Description		Guadecitabine (SGI-110) 45 mg/m^2 was administered as a subcutaneous injection on days 1-5 of each 28-day cycle. Irinotecan 125 mg/m^2 was administered IV on days 8 and 15 of each 28-day cycle.	Guadecitabine (SGI-110) 30 mg/m^2 was administered as a subcutaneous injection on days 1-5 of each 28-day cycle. Irinotecan 125 mg/m^2 was administered IV on days 8 and 15 of each 28-day cycle.	Guadecitabine (SGI-110) 30 mg/m^2 was administered as a subcutaneous injection on days 1-5 of each 28-day cycle. Irinotecan 125 mg/m^2 was administered IV on days 8 and 15 of each 28-day cycle. Growth factor support (filgrastim and peg-filgrastim) mandatory during cycle 1, and given per clinician judgement cycle 2 and beyond.	Guadecitabine (SGI-110) 45 mg/m^2 was administered as a subcutaneous injection on days 1-5 of each 28-day cycle. Irinotecan 125 mg/m^2 was administered IV on days 8 and 15 of each 28-day cycle. Growth factor support (filgrastim and peg-filgrastim) mandatory during cycle 1, and given per clinician judgement cycle 2 and beyond.	SGI-110 45 mg/m^2 was administered as a subcutaneous injection on days 1-5 of each 28-day cycle. Irinotecan 125 mg/m^2 was administered IV on days 8 and 15 of each 28-day cycle. Growth factor support (filgrastim and peg-filgrastim) was given during cycle 1 with option to give additional growth factor support at subsequent cycles per clinician judgement.	Subjects received either regorafenib or TAS-102. Regorafenib 160 mg was taken orally daily from days 1-21 of each 28-day cycle or TAS-102 35 mg/m^2 was taken orally twice daily on days 1-5 and 8-12 of each 28-day cycle. Subjects that had previously received one of these standard of care drugs (regorafenib or TAS-102) received the other on study. For subjects that had never received either regorafenib or TAS-102, the choice of therapy was deferred to the treating physician and patient.	Total of all reporting groups
Overall Number of Baseline Participants		6	3	7	6	62	34	118
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Median (Full Range); Unit of measure: Years
	Number Analyzed	6 participants	3 participants	7 participants	6 participants	62 participants	34 participants	118 participants
		54.5; (47 to 69)	64; (63 to 74)	52; (41 to 72)	54.5; (39 to 74)	55.0; (29 to 80)	59.5; (31 to 78)	57.0; (29 to 80)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	6 participants	3 participants	7 participants	6 participants	62 participants	34 participants	118 participants
	Female	2 33.3%	2 66.7%	2 28.6%	4 66.7%	21 33.9%	18 52.9%	49 41.5%
	Male	4 66.7%	1 33.3%	5 71.4%	2 33.3%	41 66.1%	16 47.1%	69 58.5%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	6 participants	3 participants	7 participants	6 participants	62 participants	34 participants	118 participants
	Hispanic or Latino	0 0.0%	0 0.0%	0 0.0%	0 0.0%	5 8.1%	1 2.9%	6 5.1%
	Not Hispanic or Latino	6 100.0%	3 100.0%	7 100.0%	6 100.0%	57 91.9%	33 97.1%	112 94.9%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	6 participants	3 participants	7 participants	6 participants	62 participants	34 participants	118 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Asian	0 0.0%	0 0.0%	0 0.0%	1 16.7%	9 14.5%	4 11.8%	14 11.9%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Black or African American	0 0.0%	0 0.0%	5 71.4%	0 0.0%	3 4.8%	8 23.5%	16 13.6%
	White	6 100.0%	3 100.0%	2 28.6%	5 83.3%	47 75.8%	22 64.7%	85 72.0%
	More than one race	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	0 0.0%	3 4.8%	0 0.0%	3 2.5%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Experiencing a Dose Limiting Toxicity
Description	Number of participants experiencing a Dose Limiting Toxicity (DLT) in each dose level. DLT is defined as any of the following study drug-related toxicities occurring during the first cycle of study drug on study: grade 4 thrombocytopenia lasting >7days; any grade 3-4 febrile neutropenia; grade 3 or higher non-hematologic toxicity unless it could be managed by supportive treatment; any other clinically significant adverse event which would place subjects at undue safety risk, or results in discontinuation of treatment.
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

Per protocol, Dose Limiting Toxicities were only assessed in Phase 1 subjects in order to determine the Phase 2 dose of SGI-110. 1 Patient in Dose Level -1G was taken off study for non-compliance due to transportation issues before completion of Cycle 1 and was not considered evaluable for DLT analysis.

Arm/Group Title	Dose Level 1	Dose Level -1	Dose Level -1G	Dose Level 1G
Arm/Group Description:	SGI-110 45 mg/m^2 subcutaneously on days 1-5 of each 28-day cycle Irinotecan 125 mg/m^2 IV on days 8 and 15 of each 28-day cycle.	SGI-110 30 mg/m^2 subcutaneously on days 1-5 of each 28-day cycle Irinotecan 125 mg/m^2 IV on days 8 and 15 of each 28-day cycle.	SGI-110 30 mg/m^2 subcutaneously on days 1-5 of each 28-day cycle Irinotecan 125 mg/m^2 IV on days 8 and 15 of each 28-day cycle. Growth Factor Support with Filgrastim and/or Pegfilgrastim given during Cycle 1 and in subsequent cycles per clinician judgement.	SGI-110 45 mg/m^2 subcutaneously on days 1-5 of each 28-day cycle Irinotecan 125 mg/m^2 IV on days 8 and 15 of each 28-day cycle. Growth Factor Support with Filgrastim and/or Pegfilgrastim given during Cycle 1 and in subsequent cycles per clinician judgement.
Overall Number of Participants Analyzed	6	3	6	6
Measure Type: Count of Participants; Unit of Measure: Participants
	1 16.7%	2 66.7%	1 16.7%	1 16.7%

2. Primary Outcome

Title	Progression Free Survival (PFS)
Description	Progression Free Survival is the time (in months) from start of treatment to progression, clinical deterioration attributed to disease, or death.
Time Frame	Up to 12 months

Outcome Measure Data

Analysis Population Description

Per protocol, the progression-free survival objective was only assessed in Phase 2 subjects. 18 subjects who received Arm B treatment were eligible to "crossover" to receive Arm A treatment. These participants were not included in the number analyzed in Arm A because they were not assessed for progression free survival after Arm A treatment.

Arm/Group Title	Phase 2: Arm A SGI-110 + Irinotecan	Phase 2: Arm B Regorafenib or TAS-102
Arm/Group Description:	SGI-110 45 mg/m^2 was administered as a subcutaneous injection on days 1-5 of each 28-day cycle. Irinotecan 125 mg/m^2 was administered IV on days 8 and 15 of each 28-day cycle. Growth factor support (filgrastim and peg-filgrastim) was given during cycle 1 with option to give additional growth factor support at subsequent cycles per clinician judgement.	Subjects received either regorafenib or TAS-102. Regorafenib 160 mg was taken orally daily from days 1-21 of each 28-day cycle or TAS-102 35 mg/m^2 was taken orally twice daily on days 1-5 and 8-12 of each 28-day cycle. Subjects that had previously received one of these standard of care drugs (regorafenib or TAS-102) received the other on study. For subjects that had never received either regorafenib or TAS-102, the choice of therapy was deferred to the treating physician and patient.
Overall Number of Participants Analyzed	62	34
Median (95% Confidence Interval); Unit of Measure: months
	2.37; (2.2 to 3.52)	2.09; (1.91 to 2.99)

3. Secondary Outcome

Title	Overall Survival
Description	Overall Survival is defined as the time (in months) between the start of treatment and death.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

Per protocol, the overall survival objective was only assessed in Phase 2 subjects. 18 subjects who received Arm B treatment and were eligible to "crossover" to receive Arm A treatment were not included in the number analyzed in Arm A because they were not assessed for overall survival after receiving Arm A treatment.

Arm/Group Title	Phase 2: Arm A SGI-110 + Irinotecan	Phase 2: Arm B Regorafenib or TAS-102
Arm/Group Description:	SGI-110 45 mg/m^2 was administered as a subcutaneous injection on days 1-5 of each 28-day cycle. Irinotecan 125 mg/m^2 was administered IV on days 8 and 15 of each 28-day cycle. Growth factor support (filgrastim and peg-filgrastim) was given during cycle 1 with option to give additional growth factor support at subsequent cycles per clinician judgement.	Subjects received either regorafenib or TAS-102. Regorafenib 160 mg was taken orally daily from days 1-21 of each 28-day cycle or TAS-102 35 mg/m^2 was taken orally twice daily on days 1-5 and 8-12 of each 28-day cycle. Subjects that had previously received one of these standard of care drugs (regorafenib or TAS-102) received the other on study. For subjects that had never received either regorafenib or TAS-102, the choice of therapy was deferred to the treating physician and patient.
Overall Number of Participants Analyzed	62	34
Median (95% Confidence Interval); Unit of Measure: months
	7.15; (6.6 to 8.02)	7.66; (4.83 to 9.36)

4. Secondary Outcome

Title	Objective Response Rate
Description	Objective Response Rate (ORR) is defined as the number of subjects achieving a Complete Response (CR) or Partial Response (PR) based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. CR = disappearance of all target lesions, PR = at least 30% decrease in the sum of diameters of target lesions.
Time Frame	Assessed until disease progression, up to 3 years

Outcome Measure Data

Analysis Population Description

ORR only assessed for Phase 2. 5 from Arm A and 2 from Arm B were excluded from response rate analysis as they didn't get a follow-up scan. 18 subjects in Arm B were eligible to "crossover" to receive Arm A treatment. They were not included in the number analyzed in Arm A because they were not assessed for objective response after Arm A treatment.

Arm/Group Title	Phase 2: Arm A SGI-110 + Irinotecan	Phase 2: Arm B Regorafenib or TAS-102
Arm/Group Description:	SGI-110 45 mg/m^2 was administered as a subcutaneous injection on days 1-5 of each 28-day cycle. Irinotecan 125 mg/m^2 was administered IV on days 8 and 15 of each 28-day cycle. Growth factor support (filgrastim and peg-filgrastim) was given during cycle 1 with option to give additional growth factor support at subsequent cycles per clinician judgement.	Subjects received either regorafenib or TAS-102. Regorafenib 160 mg was taken orally daily from days 1-21 of each 28-day cycle or TAS-102 35 mg/m^2 was taken orally twice daily on days 1-5 and 8-12 of each 28-day cycle. Subjects that had previously received one of these standard of care drugs (regorafenib or TAS-102) received the other on study. For subjects that had never received either regorafenib or TAS-102, the choice of therapy was deferred to the treating physician and patient.
Overall Number of Participants Analyzed	57	32
Measure Type: Count of Participants; Unit of Measure: Participants
	1 1.8%	0 0.0%

Adverse Events

Time Frame	Adverse Events (AEs) were collected from the first dose of study drug through 30 days after the last dose of study drug, up to 13 months
Adverse Event Reporting Description	18 patients from Arm B were eligible to "crossover" to receive Arm A study treatment after they had progression with Arm B treatment. They were assessed for adverse events after receiving Arm A treatment. Their adverse events are reported here in a separate arm.
Arm/Group Title	Phase 1: Dose Level 1	Phase 1: Dose Level -1	Phase 1: Dose Level -1G	Phase 1: Dose Level 1G	Phase 2: Arm A SGI-110 + Irinotecan	Phase 2: "Crossover" to Arm A From Arm B	Phase 2: Arm B Regorafenib or TAS-102
Arm/Group Description	Guadecitabine (SGI-110) 45 mg/m^2 was administered as a subcutaneous injection on days 1-5 of each 28-day cycle. Irinotecan 125 mg/m^2 was administered IV on days 8 and 15 of each 28-day cycle.	Guadecitabine (SGI-110) 30 mg/m^2 was administered as a subcutaneous injection on days 1-5 of each 28-day cycle. Irinotecan 125 mg/m^2 was administered IV on days 8 and 15 of each 28-day cycle.	Guadecitabine (SGI-110) 30 mg/m^2 was administered as a subcutaneous injection on days 1-5 of each 28-day cycle. Irinotecan 125 mg/m^2 was administered IV on days 8 and 15 of each 28-day cycle. Growth factor support (filgrastim and peg-filgrastim) mandatory during cycle 1, and given per clinician judgement cycle 2 and beyond.	Guadecitabine (SGI-110) 45 mg/m^2 was administered as a subcutaneous injection on days 1-5 of each 28-day cycle. Irinotecan 125 mg/m^2 was administered IV on days 8 and 15 of each 28-day cycle. Growth factor support (filgrastim and peg-filgrastim) mandatory during cycle 1, and given per clinician judgement cycle 2 and beyond.	SGI-110 45 mg/m^2 was administered as a subcutaneous injection on days 1-5 of each 28-day cycle. Irinotecan 125 mg/m^2 was administered IV on days 8 and 15 of each 28-day cycle. Growth factor support (filgrastim and peg-filgrastim) was given during cycle 1 with option to give additional growth factor support at subsequent cycles per clinician judgement.	Per protocol, Arm B subjects were given the option to "crossover" and receive Arm A study drugs after disease progression on Arm B. 18 Arm B subjects received Arm A study drugs after initial progression. SGI-110 45 mg/m^2 was administered as a subcutaneous injection on days 1-5 of each 28-day cycle. Irinotecan 125 mg/m^2 was administered IV on days 8 and 15 of each 28-day cycle. Growth factor support (filgrastim and peg-filgrastim) was given during cycle 1 with option to give additional growth factor support at subsequent cycles per clinician judgement.	Subjects received either regorafenib or TAS-102. Regorafenib 160 mg was taken orally daily from days 1-21 of each 28-day cycle or TAS-102 35 mg/m^2 was taken orally twice daily on days 1-5 and 8-12 of each 28-day cycle. Subjects that had previously received one of these standard of care drugs (regorafenib or TAS-102) received the other on study. For subjects that had never received either regorafenib or TAS-102, the choice of therapy was deferred to the treating physician and patient.
All-Cause Mortality
	Phase 1: Dose Level 1	Phase 1: Dose Level -1	Phase 1: Dose Level -1G	Phase 1: Dose Level 1G	Phase 2: Arm A SGI-110 + Irinotecan	Phase 2: "Crossover" to Arm A From Arm B	Phase 2: Arm B Regorafenib or TAS-102
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/6 (0.00%)	0/3 (0.00%)	0/7 (0.00%)	1/6 (16.67%)	3/62 (4.84%)	0/18 (0.00%)	4/34 (11.76%)
Serious Adverse Events
	Phase 1: Dose Level 1	Phase 1: Dose Level -1	Phase 1: Dose Level -1G	Phase 1: Dose Level 1G	Phase 2: Arm A SGI-110 + Irinotecan	Phase 2: "Crossover" to Arm A From Arm B	Phase 2: Arm B Regorafenib or TAS-102
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	1/6 (16.67%)	1/3 (33.33%)	2/7 (28.57%)	1/6 (16.67%)	15/62 (24.19%)	8/18 (44.44%)	1/34 (2.94%)
Blood and lymphatic system disorders
Anemia *	0/6 (0.00%)	0/3 (0.00%)	0/7 (0.00%)	0/6 (0.00%)	1/62 (1.61%)	0/18 (0.00%)	0/34 (0.00%)
Febrile neutropenia *	1/6 (16.67%)	0/3 (0.00%)	2/7 (28.57%)	0/6 (0.00%)	4/62 (6.45%)	2/18 (11.11%)	0/34 (0.00%)
Neutropenia *	0/6 (0.00%)	0/3 (0.00%)	0/7 (0.00%)	0/6 (0.00%)	1/62 (1.61%)	0/18 (0.00%)	0/34 (0.00%)
Gastrointestinal disorders
Abdominal pain *	0/6 (0.00%)	0/3 (0.00%)	0/7 (0.00%)	0/6 (0.00%)	1/62 (1.61%)	0/18 (0.00%)	0/34 (0.00%)
Colitis *	0/6 (0.00%)	0/3 (0.00%)	0/7 (0.00%)	0/6 (0.00%)	1/62 (1.61%)	0/18 (0.00%)	0/34 (0.00%)
Diarrhea *	0/6 (0.00%)	1/3 (33.33%)	1/7 (14.29%)	0/6 (0.00%)	2/62 (3.23%)	1/18 (5.56%)	0/34 (0.00%)
Nausea *	0/6 (0.00%)	0/3 (0.00%)	0/7 (0.00%)	0/6 (0.00%)	1/62 (1.61%)	0/18 (0.00%)	0/34 (0.00%)
Upper gastrointestinal hemorrhage *	0/6 (0.00%)	0/3 (0.00%)	0/7 (0.00%)	0/6 (0.00%)	0/62 (0.00%)	0/18 (0.00%)	1/34 (2.94%)
Vomiting *	0/6 (0.00%)	0/3 (0.00%)	0/7 (0.00%)	0/6 (0.00%)	1/62 (1.61%)	0/18 (0.00%)	0/34 (0.00%)
General disorders
Fatigue or Malaise *	0/6 (0.00%)	0/3 (0.00%)	0/7 (0.00%)	0/6 (0.00%)	1/62 (1.61%)	1/18 (5.56%)	0/34 (0.00%)
Fever *	1/6 (16.67%)	0/3 (0.00%)	0/7 (0.00%)	0/6 (0.00%)	0/62 (0.00%)	0/18 (0.00%)	0/34 (0.00%)
Infections and infestations
Bacteremia *	0/6 (0.00%)	0/3 (0.00%)	0/7 (0.00%)	0/6 (0.00%)	0/62 (0.00%)	1/18 (5.56%)	0/34 (0.00%)
Sepsis *	0/6 (0.00%)	0/3 (0.00%)	0/7 (0.00%)	0/6 (0.00%)	4/62 (6.45%)	3/18 (16.67%)	0/34 (0.00%)
Skin infection *	0/6 (0.00%)	0/3 (0.00%)	0/7 (0.00%)	0/6 (0.00%)	1/62 (1.61%)	0/18 (0.00%)	0/34 (0.00%)
Upper respiratory tract infection *	0/6 (0.00%)	0/3 (0.00%)	0/7 (0.00%)	0/6 (0.00%)	1/62 (1.61%)	0/18 (0.00%)	0/34 (0.00%)
Urinary tract infection *	0/6 (0.00%)	0/3 (0.00%)	0/7 (0.00%)	0/6 (0.00%)	0/62 (0.00%)	1/18 (5.56%)	0/34 (0.00%)
Wound infection *	0/6 (0.00%)	0/3 (0.00%)	0/7 (0.00%)	0/6 (0.00%)	1/62 (1.61%)	0/18 (0.00%)	0/34 (0.00%)
Investigations
Blood bilirubin increased *	0/6 (0.00%)	0/3 (0.00%)	0/7 (0.00%)	0/6 (0.00%)	1/62 (1.61%)	0/18 (0.00%)	0/34 (0.00%)
Metabolism and nutrition disorders
Dehydration *	0/6 (0.00%)	0/3 (0.00%)	0/7 (0.00%)	1/6 (16.67%)	1/62 (1.61%)	0/18 (0.00%)	0/34 (0.00%)
Musculoskeletal and connective tissue disorders
Generalized muscle weakness *	1/6 (16.67%)	0/3 (0.00%)	0/7 (0.00%)	0/6 (0.00%)	0/62 (0.00%)	0/18 (0.00%)	0/34 (0.00%)
Renal and urinary disorders
Acute kidney injury *	0/6 (0.00%)	0/3 (0.00%)	0/7 (0.00%)	1/6 (16.67%)	0/62 (0.00%)	0/18 (0.00%)	0/34 (0.00%)
Vascular disorders
Hypotension *	0/6 (0.00%)	0/3 (0.00%)	0/7 (0.00%)	0/6 (0.00%)	1/62 (1.61%)	0/18 (0.00%)	0/34 (0.00%)
* Indicates events were collected by non-systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Phase 1: Dose Level 1	Phase 1: Dose Level -1	Phase 1: Dose Level -1G	Phase 1: Dose Level 1G	Phase 2: Arm A SGI-110 + Irinotecan	Phase 2: "Crossover" to Arm A From Arm B	Phase 2: Arm B Regorafenib or TAS-102
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	6/6 (100.00%)	3/3 (100.00%)	6/7 (85.71%)	6/6 (100.00%)	58/62 (93.55%)	18/18 (100.00%)	30/34 (88.24%)
Blood and lymphatic system disorders
Anemia *	4/6 (66.67%)	2/3 (66.67%)	5/7 (71.43%)	2/6 (33.33%)	37/62 (59.68%)	8/18 (44.44%)	15/34 (44.12%)
Febrile neutropenia *	0/6 (0.00%)	2/3 (66.67%)	0/7 (0.00%)	0/6 (0.00%)	0/62 (0.00%)	3/18 (16.67%)	0/34 (0.00%)
Lymphopenia *	5/6 (83.33%)	1/3 (33.33%)	4/7 (57.14%)	3/6 (50.00%)	7/62 (11.29%)	3/18 (16.67%)	5/34 (14.71%)
Neutropenia *	6/6 (100.00%)	3/3 (100.00%)	5/7 (71.43%)	4/6 (66.67%)	27/62 (43.55%)	10/18 (55.56%)	12/34 (35.29%)
Thrombocytopenia *	3/6 (50.00%)	1/3 (33.33%)	3/7 (42.86%)	2/6 (33.33%)	20/62 (32.26%)	6/18 (33.33%)	3/34 (8.82%)
Leukopenia *	6/6 (100.00%)	1/3 (33.33%)	5/7 (71.43%)	4/6 (66.67%)	28/62 (45.16%)	6/18 (33.33%)	11/34 (32.35%)
Cardiac disorders
Sinus tachycardia *	0/6 (0.00%)	0/3 (0.00%)	0/7 (0.00%)	0/6 (0.00%)	0/62 (0.00%)	1/18 (5.56%)	1/34 (2.94%)
Endocrine disorders
Glucose intolerance *	0/6 (0.00%)	0/3 (0.00%)	0/7 (0.00%)	0/6 (0.00%)	0/62 (0.00%)	1/18 (5.56%)	0/34 (0.00%)
Gastrointestinal disorders
Abdominal pain *	2/6 (33.33%)	0/3 (0.00%)	2/7 (28.57%)	2/6 (33.33%)	5/62 (8.06%)	3/18 (16.67%)	6/34 (17.65%)
Constipation *	3/6 (50.00%)	0/3 (0.00%)	0/7 (0.00%)	1/6 (16.67%)	4/62 (6.45%)	1/18 (5.56%)	3/34 (8.82%)
Diarrhea *	2/6 (33.33%)	2/3 (66.67%)	3/7 (42.86%)	3/6 (50.00%)	24/62 (38.71%)	6/18 (33.33%)	7/34 (20.59%)
Dry mouth *	0/6 (0.00%)	0/3 (0.00%)	0/7 (0.00%)	0/6 (0.00%)	0/62 (0.00%)	0/18 (0.00%)	3/34 (8.82%)
Dyspepsia *	0/6 (0.00%)	1/3 (33.33%)	0/7 (0.00%)	1/6 (16.67%)	0/62 (0.00%)	0/18 (0.00%)	0/34 (0.00%)
Mucositis oral *	2/6 (33.33%)	0/3 (0.00%)	0/7 (0.00%)	0/6 (0.00%)	1/62 (1.61%)	2/18 (11.11%)	1/34 (2.94%)
Nausea *	5/6 (83.33%)	1/3 (33.33%)	6/7 (85.71%)	4/6 (66.67%)	28/62 (45.16%)	5/18 (27.78%)	11/34 (32.35%)
Vomiting *	0/6 (0.00%)	3/3 (100.00%)	4/7 (57.14%)	2/6 (33.33%)	9/62 (14.52%)	4/18 (22.22%)	5/34 (14.71%)
General disorders
Chills *	0/6 (0.00%)	0/3 (0.00%)	1/7 (14.29%)	1/6 (16.67%)	0/62 (0.00%)	0/18 (0.00%)	0/34 (0.00%)
Edema limbs *	1/6 (16.67%)	0/3 (0.00%)	4/7 (57.14%)	1/6 (16.67%)	1/62 (1.61%)	0/18 (0.00%)	0/34 (0.00%)
Fatigue or malaise *	3/6 (50.00%)	2/3 (66.67%)	4/7 (57.14%)	5/6 (83.33%)	37/62 (59.68%)	10/18 (55.56%)	14/34 (41.18%)
Fever *	4/6 (66.67%)	1/3 (33.33%)	2/7 (28.57%)	0/6 (0.00%)	8/62 (12.90%)	0/18 (0.00%)	1/34 (2.94%)
Injection site reaction *	4/6 (66.67%)	1/3 (33.33%)	5/7 (71.43%)	4/6 (66.67%)	12/62 (19.35%)	5/18 (27.78%)	0/34 (0.00%)
Infections and infestations
Abscess or skin infection *	1/6 (16.67%)	0/3 (0.00%)	1/7 (14.29%)	0/6 (0.00%)	0/62 (0.00%)	0/18 (0.00%)	0/34 (0.00%)
Injury, poisoning and procedural complications
Bruising *	0/6 (0.00%)	0/3 (0.00%)	0/7 (0.00%)	0/6 (0.00%)	0/62 (0.00%)	1/18 (5.56%)	0/34 (0.00%)
Infusion related reaction *	0/6 (0.00%)	0/3 (0.00%)	1/7 (14.29%)	1/6 (16.67%)	1/62 (1.61%)	0/18 (0.00%)	0/34 (0.00%)
Investigations
Alkaline phosphatase increased *	3/6 (50.00%)	1/3 (33.33%)	5/7 (71.43%)	2/6 (33.33%)	8/62 (12.90%)	0/18 (0.00%)	0/34 (0.00%)
ALT increased *	0/6 (0.00%)	0/3 (0.00%)	0/7 (0.00%)	0/6 (0.00%)	2/62 (3.23%)	0/18 (0.00%)	3/34 (8.82%)
AST increased *	2/6 (33.33%)	0/3 (0.00%)	4/7 (57.14%)	1/6 (16.67%)	2/62 (3.23%)	2/18 (11.11%)	2/34 (5.88%)
Blood bilirubin increased *	1/6 (16.67%)	0/3 (0.00%)	0/7 (0.00%)	0/6 (0.00%)	5/62 (8.06%)	1/18 (5.56%)	2/34 (5.88%)
Weight loss *	1/6 (16.67%)	0/3 (0.00%)	0/7 (0.00%)	0/6 (0.00%)	5/62 (8.06%)	1/18 (5.56%)	1/34 (2.94%)
Hyperglycemia *	0/6 (0.00%)	0/3 (0.00%)	0/7 (0.00%)	0/6 (0.00%)	2/62 (3.23%)	1/18 (5.56%)	0/34 (0.00%)
Hypocalcemia *	0/6 (0.00%)	0/3 (0.00%)	0/7 (0.00%)	0/6 (0.00%)	0/62 (0.00%)	0/18 (0.00%)	2/34 (5.88%)
Hypophosphatemia *	0/6 (0.00%)	0/3 (0.00%)	0/7 (0.00%)	0/6 (0.00%)	1/62 (1.61%)	0/18 (0.00%)	2/34 (5.88%)
Metabolism and nutrition disorders
Anorexia *	4/6 (66.67%)	0/3 (0.00%)	3/7 (42.86%)	3/6 (50.00%)	14/62 (22.58%)	2/18 (11.11%)	11/34 (32.35%)
Dehydration *	0/6 (0.00%)	1/3 (33.33%)	2/7 (28.57%)	0/6 (0.00%)	0/62 (0.00%)	0/18 (0.00%)	1/34 (2.94%)
Musculoskeletal and connective tissue disorders
Generalized muscle weakness *	0/6 (0.00%)	0/3 (0.00%)	1/7 (14.29%)	0/6 (0.00%)	0/62 (0.00%)	1/18 (5.56%)	1/34 (2.94%)
Myalgia *	1/6 (16.67%)	0/3 (0.00%)	2/7 (28.57%)	0/6 (0.00%)	3/62 (4.84%)	0/18 (0.00%)	0/34 (0.00%)
Nervous system disorders
Dizziness *	1/6 (16.67%)	1/3 (33.33%)	2/7 (28.57%)	0/6 (0.00%)	3/62 (4.84%)	0/18 (0.00%)	0/34 (0.00%)
Dysgeusia *	3/6 (50.00%)	0/3 (0.00%)	1/7 (14.29%)	0/6 (0.00%)	3/62 (4.84%)	0/18 (0.00%)	2/34 (5.88%)
Headache *	3/6 (50.00%)	0/3 (0.00%)	0/7 (0.00%)	0/6 (0.00%)	1/62 (1.61%)	0/18 (0.00%)	0/34 (0.00%)
Skin and subcutaneous tissue disorders
Alopecia *	3/6 (50.00%)	1/3 (33.33%)	2/7 (28.57%)	2/6 (33.33%)	11/62 (17.74%)	1/18 (5.56%)	1/34 (2.94%)
Palmar-plantar erythrodysesthesia *	0/6 (0.00%)	0/3 (0.00%)	0/7 (0.00%)	0/6 (0.00%)	0/62 (0.00%)	0/18 (0.00%)	2/34 (5.88%)
Vascular disorders
Hypertension *	0/6 (0.00%)	0/3 (0.00%)	0/7 (0.00%)	0/6 (0.00%)	0/62 (0.00%)	0/18 (0.00%)	2/34 (5.88%)
Hypotension *	0/6 (0.00%)	1/3 (33.33%)	1/7 (14.29%)	0/6 (0.00%)	1/62 (1.61%)	1/18 (5.56%)	0/34 (0.00%)
* Indicates events were collected by non-systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The Principal Investigators (PIs) from participating sites must provide the Johns Hopkins PI with a copy of any proposed publication for review and comment at least 30 days prior to submission.

Results Point of Contact

• Name/Title: Dr. Nilofer Azad
• Organization: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Phone: 410-614-9169
• EMail: nazad2@jhmi.edu

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Sharma A, Vatapalli R, Abdelfatah E, Wyatt McMahon K, Kerner Z, A Guzzetta A, Singh J, Zahnow C, B Baylin S, Yerram S, Hu Y, Azad N, Ahuja N. Hypomethylating agents synergize with irinotecan to improve response to chemotherapy in colorectal cancer cells. PLoS One. 2017 Apr 26;12(4):e0176139. doi: 10.1371/journal.pone.0176139. eCollection 2017. Erratum In: PLoS One. 2020 Nov 30;15(11):e0242750.

• Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• ClinicalTrials.gov Identifier: NCT01896856
• Other Study ID Numbers: J1369; NA_00085870 ( Other Identifier: JHMIRB )
• First Submitted: July 8, 2013
• First Posted: July 11, 2013
• Results First Submitted: August 24, 2020
• Results First Posted: September 14, 2020
• Last Update Posted: October 6, 2020