Trial Outcomes & Findings for Irinotecan -Eluting LC Bead-M1 (DEBIRI-M1) for Patients With Liver Metastases From Colorectal Cancer (NCT NCT02015754)

NCT ID: NCT02015754

Last Updated: 2018-03-22

Results Overview

Feasibility is defined as achieving an acceptable level of technical success in the use of DEBIRI beads treating hepatic metastases in patients with colorectal cancer.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 14 participants
• Primary outcome timeframe: 6 months
• Results posted on: 2018-03-22

Participant Flow

This study enrolled patients diagnosed with colorectal cancer with unresectable hepatic metastases who have failed or were intolerant to at least one line of systemic chemotherapy or liver-directed therapy. Patients were enrolled at Johns Hopkins to receive transarterial chemoembolization (TACE) therapy. The last patient completed in June 2015.

Participant milestones

Measure	DEBIRI DEBIRI: Irinotecan hydrochloride is a semisynthetic derivative of camptothecin, an alkaloid extracted from the tree Camptotheca acuminata. Irinotecan hydrochloride trihydrate is a pale yellow to yellow crystalline powder, it is mixed in DC Beads and injected in the tumor. LC Bead M1: The LC Bead M1, loaded with irinotecan (DEBIRI-M1) to treat patients with hepatic metastases from colorectal cancer. TACE: TACE a minimally invasive procedure performed to restrict a tumor's blood supply.
Overall Study STARTED	14
Overall Study Completed First TACE	14
Overall Study Completed First Clinical and Imaging	13
Overall Study COMPLETED	3
Overall Study NOT COMPLETED	11

Reasons for withdrawal

Measure	DEBIRI DEBIRI: Irinotecan hydrochloride is a semisynthetic derivative of camptothecin, an alkaloid extracted from the tree Camptotheca acuminata. Irinotecan hydrochloride trihydrate is a pale yellow to yellow crystalline powder, it is mixed in DC Beads and injected in the tumor. LC Bead M1: The LC Bead M1, loaded with irinotecan (DEBIRI-M1) to treat patients with hepatic metastases from colorectal cancer. TACE: TACE a minimally invasive procedure performed to restrict a tumor's blood supply.
Overall Study Disease progression	5
Overall Study Change in treatment modality	5
Overall Study Lost to Follow-up	1

Baseline Characteristics

Out of 14 enrolled participants, 10 participants identified as non-Hispanic and 4 patients did not elect to reveal their ethnicity. From the 14 participants, 9 were white, 4 were black or African American, and 1 was unknown.

Baseline characteristics by cohort

Measure	DEBIRI n=14 Participants DEBIRI: Irinotecan hydrochloride is a semisynthetic derivative of camptothecin, an alkaloid extracted from the tree Camptotheca acuminata. Irinotecan hydrochloride trihydrate is a pale yellow to yellow crystalline powder, it is mixed in DC Beads and injected in the tumor. LC Bead M1: The LC Bead M1, loaded with irinotecan (DEBIRI-M1) to treat patients with hepatic metastases from colorectal cancer. TACE: TACE a minimally invasive procedure performed to restrict a tumor's blood supply.
Age, Continuous	52.5 years n=14 Participants
Sex: Female, Male Female	8 Participants n=14 Participants
Sex: Female, Male Male	6 Participants n=14 Participants
Race/Ethnicity, Customized Non-Hispanic · White	6 Participants n=10 Participants • Out of 14 enrolled participants, 10 participants identified as non-Hispanic and 4 patients did not elect to reveal their ethnicity. From the 14 participants, 9 were white, 4 were black or African American, and 1 was unknown.
Race/Ethnicity, Customized Non-Hispanic · Black or African American	4 Participants n=10 Participants • Out of 14 enrolled participants, 10 participants identified as non-Hispanic and 4 patients did not elect to reveal their ethnicity. From the 14 participants, 9 were white, 4 were black or African American, and 1 was unknown.
Race/Ethnicity, Customized Non-Hispanic · Unknown	0 Participants n=10 Participants • Out of 14 enrolled participants, 10 participants identified as non-Hispanic and 4 patients did not elect to reveal their ethnicity. From the 14 participants, 9 were white, 4 were black or African American, and 1 was unknown.
Race/Ethnicity, Customized Unknown · White	3 Participants n=4 Participants • Out of 14 enrolled participants, 10 participants identified as non-Hispanic and 4 patients did not elect to reveal their ethnicity. From the 14 participants, 9 were white, 4 were black or African American, and 1 was unknown.
Race/Ethnicity, Customized Unknown · Black or African American	0 Participants n=4 Participants • Out of 14 enrolled participants, 10 participants identified as non-Hispanic and 4 patients did not elect to reveal their ethnicity. From the 14 participants, 9 were white, 4 were black or African American, and 1 was unknown.
Race/Ethnicity, Customized Unknown · Unknown	1 Participants n=4 Participants • Out of 14 enrolled participants, 10 participants identified as non-Hispanic and 4 patients did not elect to reveal their ethnicity. From the 14 participants, 9 were white, 4 were black or African American, and 1 was unknown.
Region of Enrollment United States	14 Participants n=14 Participants

PRIMARY outcome

Timeframe: 6 months

Population: The 14 patients received a total of 32 DEBIRI-M1 TACE procedures.

Feasibility is defined as achieving an acceptable level of technical success in the use of DEBIRI beads treating hepatic metastases in patients with colorectal cancer.

Outcome measures

Measure

DEBIRI n=32 DEBIRI-M1 Treatments DEBIRI: Irinotecan hydrochloride is a semisynthetic derivative of camptothecin, an alkaloid extracted from the tree Camptotheca acuminata. Irinotecan hydrochloride trihydrate is a pale yellow to yellow crystalline powder, it is mixed in DC Beads and injected in the tumor. LC Bead M1: The LC Bead M1, loaded with irinotecan (DEBIRI-M1) to treat patients with hepatic metastases from colorectal cancer. TACE: TACE a minimally invasive procedure performed to restrict a tumor's blood supply.

Success of DEBIRI-M1 Procedure as a Measure of Feasibility (Percentage of Successful Treatments)

100 percentage of successful treatments

PRIMARY outcome

Timeframe: 6 weeks

Population: 6-week toxicity report of device-related adverse events for all 14 participants. Classification and grading based on CTCAE v4.0.

Toxicities assessed as being at least possibly related will be recorded including system organ class, subclass, grade, frequency and time interval from DEBIRI-M1.

Outcome measures

Measure	DEBIRI n=14 Participants DEBIRI: Irinotecan hydrochloride is a semisynthetic derivative of camptothecin, an alkaloid extracted from the tree Camptotheca acuminata. Irinotecan hydrochloride trihydrate is a pale yellow to yellow crystalline powder, it is mixed in DC Beads and injected in the tumor. LC Bead M1: The LC Bead M1, loaded with irinotecan (DEBIRI-M1) to treat patients with hepatic metastases from colorectal cancer. TACE: TACE a minimally invasive procedure performed to restrict a tumor's blood supply.
Safety, Defined as Demonstrating Tolerable Device-related Toxicity Profile in the Use of DEBIRI Beads Used to Treat Hepatic Metastases in Patients With Colorectal Cancer Grade 1-2 Adverse Events · Elevated ALP	2 Participants
Safety, Defined as Demonstrating Tolerable Device-related Toxicity Profile in the Use of DEBIRI Beads Used to Treat Hepatic Metastases in Patients With Colorectal Cancer Grade 1-2 Adverse Events · Hypoalbuminemia	1 Participants
Safety, Defined as Demonstrating Tolerable Device-related Toxicity Profile in the Use of DEBIRI Beads Used to Treat Hepatic Metastases in Patients With Colorectal Cancer Grade 1-2 Adverse Events · Abdominal pain	3 Participants
Safety, Defined as Demonstrating Tolerable Device-related Toxicity Profile in the Use of DEBIRI Beads Used to Treat Hepatic Metastases in Patients With Colorectal Cancer Grade 1-2 Adverse Events · Anemia	2 Participants
Safety, Defined as Demonstrating Tolerable Device-related Toxicity Profile in the Use of DEBIRI Beads Used to Treat Hepatic Metastases in Patients With Colorectal Cancer Grade 1-2 Adverse Events · Nausea	1 Participants
Safety, Defined as Demonstrating Tolerable Device-related Toxicity Profile in the Use of DEBIRI Beads Used to Treat Hepatic Metastases in Patients With Colorectal Cancer Grade 1-2 Adverse Events · Leukopenia	1 Participants
Safety, Defined as Demonstrating Tolerable Device-related Toxicity Profile in the Use of DEBIRI Beads Used to Treat Hepatic Metastases in Patients With Colorectal Cancer Grade 1-2 Adverse Events · 30-day mortality	0 Participants
Safety, Defined as Demonstrating Tolerable Device-related Toxicity Profile in the Use of DEBIRI Beads Used to Treat Hepatic Metastases in Patients With Colorectal Cancer Grade 1-2 Adverse Events · Participants with no events	4 Participants
Safety, Defined as Demonstrating Tolerable Device-related Toxicity Profile in the Use of DEBIRI Beads Used to Treat Hepatic Metastases in Patients With Colorectal Cancer Grade 3-4 Adverse Events · Elevated ALP	0 Participants
Safety, Defined as Demonstrating Tolerable Device-related Toxicity Profile in the Use of DEBIRI Beads Used to Treat Hepatic Metastases in Patients With Colorectal Cancer Grade 3-4 Adverse Events · Hypoalbuminemia	0 Participants
Safety, Defined as Demonstrating Tolerable Device-related Toxicity Profile in the Use of DEBIRI Beads Used to Treat Hepatic Metastases in Patients With Colorectal Cancer Grade 3-4 Adverse Events · Abdominal pain	4 Participants
Safety, Defined as Demonstrating Tolerable Device-related Toxicity Profile in the Use of DEBIRI Beads Used to Treat Hepatic Metastases in Patients With Colorectal Cancer Grade 3-4 Adverse Events · Anemia	0 Participants
Safety, Defined as Demonstrating Tolerable Device-related Toxicity Profile in the Use of DEBIRI Beads Used to Treat Hepatic Metastases in Patients With Colorectal Cancer Grade 3-4 Adverse Events · Nausea	0 Participants
Safety, Defined as Demonstrating Tolerable Device-related Toxicity Profile in the Use of DEBIRI Beads Used to Treat Hepatic Metastases in Patients With Colorectal Cancer Grade 3-4 Adverse Events · Leukopenia	0 Participants
Safety, Defined as Demonstrating Tolerable Device-related Toxicity Profile in the Use of DEBIRI Beads Used to Treat Hepatic Metastases in Patients With Colorectal Cancer Grade 3-4 Adverse Events · 30-day mortality	0 Participants
Safety, Defined as Demonstrating Tolerable Device-related Toxicity Profile in the Use of DEBIRI Beads Used to Treat Hepatic Metastases in Patients With Colorectal Cancer Grade 3-4 Adverse Events · Participants with no events	10 Participants

SECONDARY outcome

Timeframe: 24 weeks

Efficacy as assessed by radiographic tumor response using the RECIST criteria at baseline and at 6-week imaging following TACE treatments.

Complete Response (CR): Disappearance of all lesions targeted by DEBIRI-M1 Partial Response (PR): At least 30% decrease in sum of longest diameter (LD) of lesions targeted by DEBIRI-M1, taking as reference the baseline sum LD Progressive Disease (PD): At least 20% increase in sum of the LD Of lesions targeted by DEBIRI-M1, taking as reference the smallest sum LD recorded since the treatment started or appearance of one or more new lesions Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, of lesions targeted by DEBIRI-M1, taking as reference the smallest sum LD since treatment started

Outcome measures

Measure	DEBIRI n=13 Participants DEBIRI: Irinotecan hydrochloride is a semisynthetic derivative of camptothecin, an alkaloid extracted from the tree Camptotheca acuminata. Irinotecan hydrochloride trihydrate is a pale yellow to yellow crystalline powder, it is mixed in DC Beads and injected in the tumor. LC Bead M1: The LC Bead M1, loaded with irinotecan (DEBIRI-M1) to treat patients with hepatic metastases from colorectal cancer. TACE: TACE a minimally invasive procedure performed to restrict a tumor's blood supply.
Efficacy - Tumor Response by RECIST Complete Response	0 Participants
Efficacy - Tumor Response by RECIST Partial Response	1 Participants
Efficacy - Tumor Response by RECIST Stable Disease	8 Participants
Efficacy - Tumor Response by RECIST Progressive Disease	4 Participants
Efficacy - Tumor Response by RECIST Objective response (CR + PR)	1 Participants
Efficacy - Tumor Response by RECIST Disease control rate (CR + PR + SD)	9 Participants

SECONDARY outcome

Timeframe: 24 weeks

Efficacy as assessed by radiographic tumor response using modified RECIST (mRECIST) criteria at baseline and at 6-week imaging following TACE treatments.

Complete Response (CR): Disappearance of any intratumoral arterial enhancement in all target lesions Partial Response (PR): At least 30% decrease in the sum of diameters of viable target lesions, taking as reference the baseline sum of the diameters of target lesions Progressive Disease (PD): At least 20% increase in sum of diameters of viable target lesions, taking as reference the smallest sum of diameters of viable target lesions since treatment started.

Stable Disease (SD): Any cases that do not qualify for either PR or PD.

Outcome measures

Measure	DEBIRI n=13 Participants DEBIRI: Irinotecan hydrochloride is a semisynthetic derivative of camptothecin, an alkaloid extracted from the tree Camptotheca acuminata. Irinotecan hydrochloride trihydrate is a pale yellow to yellow crystalline powder, it is mixed in DC Beads and injected in the tumor. LC Bead M1: The LC Bead M1, loaded with irinotecan (DEBIRI-M1) to treat patients with hepatic metastases from colorectal cancer. TACE: TACE a minimally invasive procedure performed to restrict a tumor's blood supply.
Efficacy - Tumor Response by mRECIST Complete Response	0 Participants
Efficacy - Tumor Response by mRECIST Partial Response	0 Participants
Efficacy - Tumor Response by mRECIST Stable Disease	9 Participants
Efficacy - Tumor Response by mRECIST Progressive Disease	4 Participants
Efficacy - Tumor Response by mRECIST Objective response (CR + PR)	0 Participants
Efficacy - Tumor Response by mRECIST Disease control rate (CR + PR + SD)	9 Participants

SECONDARY outcome

Timeframe: 24 weeks

Efficacy as assessed by radiographic tumor response using EASL amendment at baseline and at 6-week imaging following TACE treatments.

Complete Response (CR): Achieving 100% tumor necrosis of lesions targeted by DEBIRI-M1. Baseline degree of tumor enhancement used as a reference.

Partial Response (PR): Demonstrating greater than 50% tumor necrosis in lesions targeted by DEBIRI-M1.

Stable Disease (SD): Not meeting requirements for CR or PR and not demonstrating evidence of progression of lesions targeted by DEBIRI-M1.

Progressive Disease (PD): Reappearance of or increased tumor enhancement greater than 25% in lesions previously targeted by DEBIRI-M1.

Outcome measures

Measure	DEBIRI n=13 Participants DEBIRI: Irinotecan hydrochloride is a semisynthetic derivative of camptothecin, an alkaloid extracted from the tree Camptotheca acuminata. Irinotecan hydrochloride trihydrate is a pale yellow to yellow crystalline powder, it is mixed in DC Beads and injected in the tumor. LC Bead M1: The LC Bead M1, loaded with irinotecan (DEBIRI-M1) to treat patients with hepatic metastases from colorectal cancer. TACE: TACE a minimally invasive procedure performed to restrict a tumor's blood supply.
Efficacy -Tumor Response by European Association for the Study of the Liver (EASL) Criteria Progressive Disease	6 Participants
Efficacy -Tumor Response by European Association for the Study of the Liver (EASL) Criteria Objective response (CR + PR)	3 Participants
Efficacy -Tumor Response by European Association for the Study of the Liver (EASL) Criteria Stable Disease	4 Participants
Efficacy -Tumor Response by European Association for the Study of the Liver (EASL) Criteria Complete Response	0 Participants
Efficacy -Tumor Response by European Association for the Study of the Liver (EASL) Criteria Partial Response	3 Participants
Efficacy -Tumor Response by European Association for the Study of the Liver (EASL) Criteria Disease control rate (CR + PR + SD)	7 Participants

SECONDARY outcome

Timeframe: 24 weeks

Efficacy as assessed by radiographic tumor response using WHO criteria at baseline and at 6-week imaging following TACE treatments.

Complete Response (CR): No lesions detected for at least 4 weeks. Partial Response (PR): 50% or greater decrease in the sum of the products of diameters Stable Disease (SD): Cases that do not fit the criteria of PR or PD. Progressive Disease (PD): 25% or greater increase in the sum of the products of diameters in one or more lesions; or new lesions

Outcome measures

Measure	DEBIRI n=13 Participants DEBIRI: Irinotecan hydrochloride is a semisynthetic derivative of camptothecin, an alkaloid extracted from the tree Camptotheca acuminata. Irinotecan hydrochloride trihydrate is a pale yellow to yellow crystalline powder, it is mixed in DC Beads and injected in the tumor. LC Bead M1: The LC Bead M1, loaded with irinotecan (DEBIRI-M1) to treat patients with hepatic metastases from colorectal cancer. TACE: TACE a minimally invasive procedure performed to restrict a tumor's blood supply.
Efficacy - Tumor Response by World Health Organization (WHO) Criteria Progressive Disease	3 Participants
Efficacy - Tumor Response by World Health Organization (WHO) Criteria Objective response (CR + PR)	1 Participants
Efficacy - Tumor Response by World Health Organization (WHO) Criteria Disease control rate (CR + PR + SD)	10 Participants
Efficacy - Tumor Response by World Health Organization (WHO) Criteria Complete Response	0 Participants
Efficacy - Tumor Response by World Health Organization (WHO) Criteria Partial Response	1 Participants
Efficacy - Tumor Response by World Health Organization (WHO) Criteria Stable Disease	9 Participants

SECONDARY outcome

Timeframe: 6 weeks

Population: 2 out of original 14 patients had no CEA measurements.

CEA measurements pre- and post- DEBIRI treatment will be recorded to ascertain if it is predictive of survival.

Outcome measures

Measure

DEBIRI n=12 Participants DEBIRI: Irinotecan hydrochloride is a semisynthetic derivative of camptothecin, an alkaloid extracted from the tree Camptotheca acuminata. Irinotecan hydrochloride trihydrate is a pale yellow to yellow crystalline powder, it is mixed in DC Beads and injected in the tumor. LC Bead M1: The LC Bead M1, loaded with irinotecan (DEBIRI-M1) to treat patients with hepatic metastases from colorectal cancer. TACE: TACE a minimally invasive procedure performed to restrict a tumor's blood supply.

Number of Participants With Change in Carcinoembryonic Antigen (CEA)

6 participants

SECONDARY outcome

Timeframe: Up to 26 months

Median overall survival from start of therapy (DEBIRI #1) until death (or date of censor).

Outcome measures

Measure

DEBIRI n=14 Participants DEBIRI: Irinotecan hydrochloride is a semisynthetic derivative of camptothecin, an alkaloid extracted from the tree Camptotheca acuminata. Irinotecan hydrochloride trihydrate is a pale yellow to yellow crystalline powder, it is mixed in DC Beads and injected in the tumor. LC Bead M1: The LC Bead M1, loaded with irinotecan (DEBIRI-M1) to treat patients with hepatic metastases from colorectal cancer. TACE: TACE a minimally invasive procedure performed to restrict a tumor's blood supply.

Median Overall Survival

18.7 months Interval 1.1 to 25.83

SECONDARY outcome

Timeframe: 1 year

Percentage of study patients surviving after one year from initial treatment analyzed with Kaplan-Meier curve.

Outcome measures

Measure

DEBIRI n=14 Participants DEBIRI: Irinotecan hydrochloride is a semisynthetic derivative of camptothecin, an alkaloid extracted from the tree Camptotheca acuminata. Irinotecan hydrochloride trihydrate is a pale yellow to yellow crystalline powder, it is mixed in DC Beads and injected in the tumor. LC Bead M1: The LC Bead M1, loaded with irinotecan (DEBIRI-M1) to treat patients with hepatic metastases from colorectal cancer. TACE: TACE a minimally invasive procedure performed to restrict a tumor's blood supply.

One-year Survival Percentage

36 percentage of participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 24 hours

PK analysis of irinotecan and its metabolite SN-38 in the first 10 patients enrolled on protocol including peak plasma concentration (Cmax). Time points assessed in protocol were pre-dose, and then 5min, 10min, 15min, 30min, 1hr, 2hr, 4hr, 6hr, and 24hr post administration of 100mg irinotecan.

Outcome measures

Measure	DEBIRI n=10 Participants DEBIRI: Irinotecan hydrochloride is a semisynthetic derivative of camptothecin, an alkaloid extracted from the tree Camptotheca acuminata. Irinotecan hydrochloride trihydrate is a pale yellow to yellow crystalline powder, it is mixed in DC Beads and injected in the tumor. LC Bead M1: The LC Bead M1, loaded with irinotecan (DEBIRI-M1) to treat patients with hepatic metastases from colorectal cancer. TACE: TACE a minimally invasive procedure performed to restrict a tumor's blood supply.
Exploratory Endpoint - Pharmacokinetic (PK) Profile of Irinotecan and SN-38 Post DEBIRI-TACE Cmax irinotecan	1299 ng/mL Standard Deviation 2276
Exploratory Endpoint - Pharmacokinetic (PK) Profile of Irinotecan and SN-38 Post DEBIRI-TACE Cmax SN-38	41.5 ng/mL Standard Deviation 26.1

OTHER_PRE_SPECIFIED outcome

Timeframe: 24 hours

Total drug exposure over time (AUC) of irinotecan and its metabolite SN-38 post DEBIRI-TACE in the first 10 patients enrolled on protocol. Time points assessed in protocol were pre-dose, and then 5min, 10min, 15min, 30min, 1hr, 2hr, 4hr, 6hr, and 24hr post administration of 100mg irinotecan.

Outcome measures

Measure	DEBIRI n=10 Participants DEBIRI: Irinotecan hydrochloride is a semisynthetic derivative of camptothecin, an alkaloid extracted from the tree Camptotheca acuminata. Irinotecan hydrochloride trihydrate is a pale yellow to yellow crystalline powder, it is mixed in DC Beads and injected in the tumor. LC Bead M1: The LC Bead M1, loaded with irinotecan (DEBIRI-M1) to treat patients with hepatic metastases from colorectal cancer. TACE: TACE a minimally invasive procedure performed to restrict a tumor's blood supply.
Exploratory Endpoint -Total Drug Exposure Over Time (AUC) of Irinotecan and SN-38 Post DEBIRI-TACE AUC irinotecan	5020 ng*h/mL Standard Deviation 2138
Exploratory Endpoint -Total Drug Exposure Over Time (AUC) of Irinotecan and SN-38 Post DEBIRI-TACE AUC SN-38	305 ng*h/mL Standard Deviation 206

OTHER_PRE_SPECIFIED outcome

Timeframe: 24 hours

Time taken to reach maximum concentration (Tmax) of irinotecan and its metabolite SN-38 post DEBIRI-TACE in the first 10 patients enrolled on protocol. Time points assessed in protocol were pre-dose, and then 5min, 10min, 15min, 30min, 1hr, 2hr, 4hr, 6hr, and 24hr post administration of 100mg irinotecan.

Outcome measures

Measure	DEBIRI n=10 Participants DEBIRI: Irinotecan hydrochloride is a semisynthetic derivative of camptothecin, an alkaloid extracted from the tree Camptotheca acuminata. Irinotecan hydrochloride trihydrate is a pale yellow to yellow crystalline powder, it is mixed in DC Beads and injected in the tumor. LC Bead M1: The LC Bead M1, loaded with irinotecan (DEBIRI-M1) to treat patients with hepatic metastases from colorectal cancer. TACE: TACE a minimally invasive procedure performed to restrict a tumor's blood supply.
Exploratory Endpoint -Tmax of Irinotecan and SN-38 Post DEBIRI-TACE Tmax of irinotecan	.95 hours Standard Deviation .77
Exploratory Endpoint -Tmax of Irinotecan and SN-38 Post DEBIRI-TACE Tmax of SN-38	1.26 hours Standard Deviation .54

OTHER_PRE_SPECIFIED outcome

Timeframe: 24 hours

Plasma half-life (t 1/2) of irinotecan and its metabolite SN-38 post DEBIRI-TACE in the first 10 patients enrolled on protocol. Time points assessed in protocol were pre-dose, and then 5min, 10min, 15min, 30min, 1hr, 2hr, 4hr, 6hr, and 24hr post administration of 100mg irinotecan.

Outcome measures

Measure	DEBIRI n=10 Participants DEBIRI: Irinotecan hydrochloride is a semisynthetic derivative of camptothecin, an alkaloid extracted from the tree Camptotheca acuminata. Irinotecan hydrochloride trihydrate is a pale yellow to yellow crystalline powder, it is mixed in DC Beads and injected in the tumor. LC Bead M1: The LC Bead M1, loaded with irinotecan (DEBIRI-M1) to treat patients with hepatic metastases from colorectal cancer. TACE: TACE a minimally invasive procedure performed to restrict a tumor's blood supply.
Plasma Half-life of Irinotecan and SN-38 Post DEBIRI-TACE t 1/2 irinotecan	5.7 hours Standard Deviation 1.2
Plasma Half-life of Irinotecan and SN-38 Post DEBIRI-TACE t 1/2 SN-38	8.6 hours Standard Deviation 2.6

OTHER_PRE_SPECIFIED outcome

Timeframe: 24 hours

Changes in vascular endothelial growth factors (VEGF), VEGF receptors VEGFR1 and VEGFR2 pre- and post- DEBIRI treatment examined for significant effects as well as association with DEBIRI treatment. One-sample Wilcoxon signed rank test was utilized to compare whether %change of VEGF, VEGFR1, or VEGFR2 from baseline was equal to 0. For groups with non-zero percent changes, the 95% confidence intervals were provided.

Outcome measures

Measure	DEBIRI n=14 Participants DEBIRI: Irinotecan hydrochloride is a semisynthetic derivative of camptothecin, an alkaloid extracted from the tree Camptotheca acuminata. Irinotecan hydrochloride trihydrate is a pale yellow to yellow crystalline powder, it is mixed in DC Beads and injected in the tumor. LC Bead M1: The LC Bead M1, loaded with irinotecan (DEBIRI-M1) to treat patients with hepatic metastases from colorectal cancer. TACE: TACE a minimally invasive procedure performed to restrict a tumor's blood supply.
Exploratory Endpoint - Angiogenesis VEGFR2 (24 hours post)	5.51 % change from baseline Interval -5.24 to 18.7
Exploratory Endpoint - Angiogenesis VEGF (immediately post)	-2.66 % change from baseline Interval -19.5 to 6.45
Exploratory Endpoint - Angiogenesis VEGF (24 hours post)	6.37 % change from baseline Interval -6.03 to 43.0
Exploratory Endpoint - Angiogenesis VEGFR1 (immediately post)	4.02 % change from baseline Interval -13.7 to 19.8
Exploratory Endpoint - Angiogenesis VEGFR1 (24 hours post)	-37.9 % change from baseline Interval -45.6 to -19.6
Exploratory Endpoint - Angiogenesis VEGFR2 (immediately post)	4.49 % change from baseline Interval -2.07 to 11.2

Adverse Events

DEBIRI

Serious events: 1 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Measure

DEBIRI n=14 participants at risk DEBIRI: Irinotecan hydrochloride is a semisynthetic derivative of camptothecin, an alkaloid extracted from the tree Camptotheca acuminata. Irinotecan hydrochloride trihydrate is a pale yellow to yellow crystalline powder, it is mixed in DC Beads and injected in the tumor. LC Bead M1: The LC Bead M1, loaded with irinotecan (DEBIRI-M1) to treat patients with hepatic metastases from colorectal cancer. TACE: TACE a minimally invasive procedure performed to restrict a tumor's blood supply.

Renal and urinary disorders Acute kidney injury

7.1% 1/14 • Number of events 1 • Adverse events collected through study completion, an average of 6 months.

Other adverse events

Measure	DEBIRI n=14 participants at risk DEBIRI: Irinotecan hydrochloride is a semisynthetic derivative of camptothecin, an alkaloid extracted from the tree Camptotheca acuminata. Irinotecan hydrochloride trihydrate is a pale yellow to yellow crystalline powder, it is mixed in DC Beads and injected in the tumor. LC Bead M1: The LC Bead M1, loaded with irinotecan (DEBIRI-M1) to treat patients with hepatic metastases from colorectal cancer. TACE: TACE a minimally invasive procedure performed to restrict a tumor's blood supply.
Gastrointestinal disorders Abdominal pain	78.6% 11/14 • Number of events 12 • Adverse events collected through study completion, an average of 6 months.
Gastrointestinal disorders Dyspepsia	14.3% 2/14 • Number of events 2 • Adverse events collected through study completion, an average of 6 months.
Gastrointestinal disorders Gastroesophageal reflux disease	14.3% 2/14 • Number of events 2 • Adverse events collected through study completion, an average of 6 months.
Blood and lymphatic system disorders Anemia	42.9% 6/14 • Number of events 7 • Adverse events collected through study completion, an average of 6 months.
Metabolism and nutrition disorders Anorexia	7.1% 1/14 • Number of events 1 • Adverse events collected through study completion, an average of 6 months.
Gastrointestinal disorders Ascites	7.1% 1/14 • Number of events 1 • Adverse events collected through study completion, an average of 6 months.
General disorders Non-cardiac chest pain	14.3% 2/14 • Number of events 2 • Adverse events collected through study completion, an average of 6 months.
General disorders Chills	7.1% 1/14 • Number of events 1 • Adverse events collected through study completion, an average of 6 months.
Nervous system disorders Concentration impairment	7.1% 1/14 • Number of events 1 • Adverse events collected through study completion, an average of 6 months.
Gastrointestinal disorders Constipation	28.6% 4/14 • Number of events 7 • Adverse events collected through study completion, an average of 6 months.
Respiratory, thoracic and mediastinal disorders Cough	7.1% 1/14 • Number of events 1 • Adverse events collected through study completion, an average of 6 months.
Gastrointestinal disorders Diarrhea	14.3% 2/14 • Number of events 2 • Adverse events collected through study completion, an average of 6 months.
Nervous system disorders Dysgeusia	7.1% 1/14 • Number of events 1 • Adverse events collected through study completion, an average of 6 months.
Investigations Alanine aminotransferase increased	14.3% 2/14 • Number of events 3 • Adverse events collected through study completion, an average of 6 months.
Investigations Alkaline phosphatase increased	50.0% 7/14 • Number of events 7 • Adverse events collected through study completion, an average of 6 months.
Investigations Aspartate aminotransferase increased	14.3% 2/14 • Number of events 2 • Adverse events collected through study completion, an average of 6 months.
Investigations INR increased	21.4% 3/14 • Number of events 3 • Adverse events collected through study completion, an average of 6 months.
General disorders Fatigue	57.1% 8/14 • Number of events 12 • Adverse events collected through study completion, an average of 6 months.
General disorders Fever	7.1% 1/14 • Number of events 1 • Adverse events collected through study completion, an average of 6 months.
General disorders Flu like symptoms	7.1% 1/14 • Number of events 1 • Adverse events collected through study completion, an average of 6 months.
Investigations Blood bilirubin increased	7.1% 1/14 • Number of events 1 • Adverse events collected through study completion, an average of 6 months.
Metabolism and nutrition disorders Hyperglycemia	50.0% 7/14 • Number of events 8 • Adverse events collected through study completion, an average of 6 months.
Metabolism and nutrition disorders Hyperkalemia	7.1% 1/14 • Number of events 1 • Adverse events collected through study completion, an average of 6 months.
Vascular disorders Hypertension	21.4% 3/14 • Number of events 4 • Adverse events collected through study completion, an average of 6 months.
Metabolism and nutrition disorders Hypoalbuminemia	7.1% 1/14 • Number of events 1 • Adverse events collected through study completion, an average of 6 months.
Metabolism and nutrition disorders Hypoglycemia	14.3% 2/14 • Number of events 2 • Adverse events collected through study completion, an average of 6 months.
Skin and subcutaneous tissue disorders Pruritus	7.1% 1/14 • Number of events 2 • Adverse events collected through study completion, an average of 6 months.
Musculoskeletal and connective tissue disorders Pain in extremity	14.3% 2/14 • Number of events 2 • Adverse events collected through study completion, an average of 6 months.
Investigations White blood cell decreased	14.3% 2/14 • Number of events 4 • Adverse events collected through study completion, an average of 6 months.
Investigations Lymphocyte count decreased	35.7% 5/14 • Number of events 7 • Adverse events collected through study completion, an average of 6 months.
Gastrointestinal disorders Nausea	28.6% 4/14 • Number of events 6 • Adverse events collected through study completion, an average of 6 months.
Investigations Neutrophil count decreased	7.1% 1/14 • Number of events 1 • Adverse events collected through study completion, an average of 6 months.
Vascular disorders Hot flashes	7.1% 1/14 • Number of events 1 • Adverse events collected through study completion, an average of 6 months.
Musculoskeletal and connective tissue disorders Back pain	21.4% 3/14 • Number of events 4 • Adverse events collected through study completion, an average of 6 months.
Investigations Platelet count decreased	21.4% 3/14 • Number of events 3 • Adverse events collected through study completion, an average of 6 months.
Gastrointestinal disorders Vomiting	14.3% 2/14 • Number of events 2 • Adverse events collected through study completion, an average of 6 months.

Additional Information

Jean-Francois Geschwind, MD

Yale University

Phone: 203-785-5865

Email: jeff.geschwind@yale.edu

Results disclosure agreements

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