Trial Outcomes & Findings for Open-Label Phase IIb Efficacy Trial of Cancer Macrobeads Compared to Best Supportive Care in Colorectal Cancer Patients (NCT NCT02046174)

NCT ID: NCT02046174

Last Updated: 2021-03-24

Results Overview

The primary objective of this study was to evaluate the efficacy of RENCA macrobead implantation as assessed by overall survival in subjects with treatment-resistant mCRC.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

70 participants

Primary outcome timeframe

From date of the most recent scan prior to the first macrobead implantation; assessed up to 32 months.

Results posted on

2021-03-24

Participant Flow

Participants were recruited based on physician referral at five academic medical centers between March 2013 and November 2017. The first participant was implanted on April 11, 2014 and the last implant was March 7, 2018.

70 participants provided informed consent to participate in the study (Group A n=67; Group B n=3). Of these, 41 mCRC patients were enrolled in the RENCA macrobead implantation arm (Group A) and 3 subjects were enrolled in the Best Supportive Care arm (Group B). The 25 subjects who were not enrolled into Group A, after providing informed consent, had failed the respective eligibility criteria.

Participant milestones

Participant milestones
Measure	Macrobead Implantation Arm mCRC patients who will undergo up to 4 implantations of RENCA macrobeads (no less than 3 months apart), at a dosage level of 8 RENCA macrobeads per kilogram of body weight. RENCA macrobeads	Best Supportive Care Arm mCRC patients who had previously decided (independently of this study) to receive, or continue receiving, best supportive care, defined as management of symptoms aimed at maintaining or improving quality of life, but not including approved therapies targeting the patient's malignancy.
Overall Study STARTED	42	3
Overall Study COMPLETED	41	3
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Macrobead Implantation Arm mCRC patients who will undergo up to 4 implantations of RENCA macrobeads (no less than 3 months apart), at a dosage level of 8 RENCA macrobeads per kilogram of body weight. RENCA macrobeads	Best Supportive Care Arm mCRC patients who had previously decided (independently of this study) to receive, or continue receiving, best supportive care, defined as management of symptoms aimed at maintaining or improving quality of life, but not including approved therapies targeting the patient's malignancy.
Overall Study Too many adhesions to receive implant (at time of surgery).	1	0

Baseline Characteristics

Open-Label Phase IIb Efficacy Trial of Cancer Macrobeads Compared to Best Supportive Care in Colorectal Cancer Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Macrobead Implantation Arm n=41 Participants mCRC patients who will undergo up to 4 implantations of RENCA macrobeads (no less than 3 months apart), at a dosage level of 8 RENCA macrobeads per kilogram of body weight.
Age, Continuous	55.9 years STANDARD_DEVIATION 14.67 • n=5 Participants
Sex: Female, Male Female	21 Participants n=5 Participants
Sex: Female, Male Male	20 Participants n=5 Participants
Race/Ethnicity, Customized White	33 Participants n=5 Participants
Race/Ethnicity, Customized African American	4 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic	3 Participants n=5 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants
Region of Enrollment United States	41 Participants n=5 Participants

PRIMARY outcome

Timeframe: From date of the most recent scan prior to the first macrobead implantation; assessed up to 32 months.

Population: The analysis population was limited to those in Group A, Macrobead Implantation Arm. Group B, Best Supportive Care, was only able to enroll 3 of 80 participants planned. Per Group B investigators, the entry criteria were flagged as being impossible for reliable enrollment. Therefore, these results focus on the participants who were enrolled and implanted with RENCA macrobeads.

The primary objective of this study was to evaluate the efficacy of RENCA macrobead implantation as assessed by overall survival in subjects with treatment-resistant mCRC.

Outcome measures

Outcome measures
Measure	Macrobead Implantation Arm n=41 Participants mCRC patients who will undergo up to 4 implantations of RENCA macrobeads (no less than 3 months apart), at a dosage level of 8 RENCA macrobeads per kilogram of body weight.	Implant 1: Day 14 ECOG score at day 14 after first implantation	Implant 1: Day 30 ECOG score at day 30 following first implantation	Implant 1: Day 60 ECOG score at day 60 following first implantation	Implant 2: Day 0 ECOG score at day 0 of second implantation	Implant 2: Day 14 ECOG score at day 14 following second implantation	Implant 2: Day 30 ECOG score at day 30 following second implantation	Implant 2: Day 60 ECOG score at day 60 following second implantation
Overall Survival	9.25 months Interval 6.03 to 11.44	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline; Day 14, 30, 60 post-Implant 1; Day 14, 30, 60 post-Implant 2

Population: Analysis population was limited to the arm "macrobead implantation" as the proposed second arm "best supportive care" did not enroll enough participants to facilitate reliable analysis. Implant 1 (day 0 to day 60): Participants who received at least one RENCA macrobead implantation; Implant 2 (day 0 to day 60): Participants who received at least two RENCA macrobead implantations.

The Eastern Cooperative Oncology Group (ECOG) performance scale is a 5-point scale, where 0 denotes perfect health and 5 is death. It is used by clinicians to assess disease progression and how the disease is affecting the daily living abilities of the patient. The ECOG Performance Status scores are defined as follows: * 0: Fully active, able to carry on all pre-disease activities without restriction. * 1: Restricted in physical strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature (e.g. light house work, office work). * 2: Ambulatory and capable of all self-care, but unable to carry out any work activities, up and about more than 50% of waking hours. * 3: Capable of only limited self-care, confined to bed or chair 50% or more of waking hours. * 4: Completely disabled, cannot carry on any self-care, totally confined to bed or chair. * 5: Death

Outcome measures

Outcome measures
Measure	Macrobead Implantation Arm n=41 Participants mCRC patients who will undergo up to 4 implantations of RENCA macrobeads (no less than 3 months apart), at a dosage level of 8 RENCA macrobeads per kilogram of body weight.	Implant 1: Day 14 n=38 Participants ECOG score at day 14 after first implantation	Implant 1: Day 30 n=36 Participants ECOG score at day 30 following first implantation	Implant 1: Day 60 n=27 Participants ECOG score at day 60 following first implantation	Implant 2: Day 0 n=8 Participants ECOG score at day 0 of second implantation	Implant 2: Day 14 n=8 Participants ECOG score at day 14 following second implantation	Implant 2: Day 30 n=7 Participants ECOG score at day 30 following second implantation	Implant 2: Day 60 n=7 Participants ECOG score at day 60 following second implantation
Performance Status (ECOG Score) ECOG Score 3	0 Participants	2 Participants	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Performance Status (ECOG Score) ECOG Score 0	16 Participants	5 Participants	5 Participants	11 Participants	5 Participants	4 Participants	4 Participants	4 Participants
Performance Status (ECOG Score) ECOG Score 1	21 Participants	23 Participants	23 Participants	8 Participants	2 Participants	3 Participants	2 Participants	2 Participants
Performance Status (ECOG Score) ECOG Score 2	4 Participants	7 Participants	7 Participants	7 Participants	1 Participants	1 Participants	1 Participants	1 Participants
Performance Status (ECOG Score) ECOG Score 4	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Performance Status (ECOG Score) ECOG Score 5	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline; Day 14, 30, 60 post-Implant 1; Day 14, 30, 60 post-Implant 2

Population: Analysis population was limited to the arm "macrobead implantation" as the proposed second arm "best supportive care" did not enroll enough participants to facilitate reliable analysis. Implant 1 (Day 0 to Day 60): Participants who had received at least 1 RENCA macrobead implantation; Implant 2 (Day 0 to Day 60): Participants who had received at least 2 RENCA macrobead implantations.

Karnofsky Performance Status (KPS) is a self-rated scale that measures the participant's ability to perform daily functions, ranging from 0 ("dead") to 100 ("normal, no complaints, no evidence of disease). Karnofsky scores are defined as follows: * 100: Normal; no complaints; no evidence of disease * 90: Able to carry on normal activity with effort, minor sign or symptoms of disease * 80: Normal activity with effort; some sign or symptoms of disease * 70: Cares for self; unable to carry on normal activity or do active work * 60: Requires occasional assistance, but is able to care for most personal needs * 50: Requires considerable assistance and frequent medical care * 40: Disabled; requires special care and assistance * 30: Severely disabled; hospitalization is indicated, although death is not imminent * 20: Very sick; hospitalization/active support treatment is necessary * 10: Moribund; fatal processes progressively worsening * 0: Dead

Outcome measures

Outcome measures
Measure	Macrobead Implantation Arm n=40 Participants mCRC patients who will undergo up to 4 implantations of RENCA macrobeads (no less than 3 months apart), at a dosage level of 8 RENCA macrobeads per kilogram of body weight.	Implant 1: Day 14 n=39 Participants ECOG score at day 14 after first implantation	Implant 1: Day 30 n=34 Participants ECOG score at day 30 following first implantation	Implant 1: Day 60 n=26 Participants ECOG score at day 60 following first implantation	Implant 2: Day 0 n=7 Participants ECOG score at day 0 of second implantation	Implant 2: Day 14 n=8 Participants ECOG score at day 14 following second implantation	Implant 2: Day 30 n=7 Participants ECOG score at day 30 following second implantation	Implant 2: Day 60 n=7 Participants ECOG score at day 60 following second implantation
Activities of Daily Living (KPS Score)	88.3 score on a scale Standard Deviation 9.6	82.1 score on a scale Standard Deviation 13.6	74.3 score on a scale Standard Deviation 23.7	81.8 score on a scale Standard Deviation 19.1	94.3 score on a scale Standard Deviation 5.4	83.3 score on a scale Standard Deviation 16.7	93.3 score on a scale Standard Deviation 7.7	91.4 score on a scale Standard Deviation 9.9

SECONDARY outcome

Timeframe: Baseline; Day 14, 30, 60 post-Implant 1; Day 14, 30, 60 post-Implant 2

Population: Analysis population was limited to the arm "macrobead implantation" as the proposed second arm "best supportive care" did not enroll enough participants to facilitate reliable analysis. Implant 1 (Day 0 to Day 60): Participants who had received at least 1 RENCA macrobead implantation; Implant 2 (Day 0 to Day 60): Participants who had received at least 2 RENCA macrobead implantations.

The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30, version 3.0) consists of 30 questions which pertain to: five functional scales, three symptom scales, a global health status score, and six single items. The Global Health Status is assessed from 2 of the 30 questions (Question 29 and 30), whose response score ranges on a 7 point scale. The score for physical function is calculated based on the average score from these 2 questions. A linear transformation is used to standardize these responses. Using this linear transformation, the minimum value is 0 (worst outcome, poor) and the maximum value is 100 (best outcome, excellent). Therefore, increasing values indicate better outcome and decreasing values indicate worse outcome.

Outcome measures

Outcome measures
Measure	Macrobead Implantation Arm n=41 Participants mCRC patients who will undergo up to 4 implantations of RENCA macrobeads (no less than 3 months apart), at a dosage level of 8 RENCA macrobeads per kilogram of body weight.	Implant 1: Day 14 n=39 Participants ECOG score at day 14 after first implantation	Implant 1: Day 30 n=34 Participants ECOG score at day 30 following first implantation	Implant 1: Day 60 n=26 Participants ECOG score at day 60 following first implantation	Implant 2: Day 0 n=8 Participants ECOG score at day 0 of second implantation	Implant 2: Day 14 n=8 Participants ECOG score at day 14 following second implantation	Implant 2: Day 30 n=7 Participants ECOG score at day 30 following second implantation	Implant 2: Day 60 n=7 Participants ECOG score at day 60 following second implantation
Global Health Status	68.70 score on a scale Standard Deviation 22.03	50.21 score on a scale Standard Deviation 24.37	56.13 score on a scale Standard Deviation 29.61	69.87 score on a scale Standard Deviation 28.48	84.38 score on a scale Standard Deviation 17.50	75.00 score on a scale Standard Deviation 14.77	83.33 score on a scale Standard Deviation 11.79	83.33 score on a scale Standard Deviation 26.79

SECONDARY outcome

Timeframe: Baseline; Day 14, 30, 60 post-Implant 1; Day 14, 30, 60 post-Implant 2

Population: Analysis population was limited to the arm "macrobead implantation" as the proposed second arm "best supportive care" did not enroll enough participants to facilitate reliable analysis. Implant 1 (Day 0 to Day 60): Participants who had received at least 1 RENCA macrobead implantation; Implant 2 (Day 0 to Day 60): Participants who had received at least 2 RENCA macrobead implantations.

TThe European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30, version 3.0) consists of 30 questions which pertain to: five functional scales (including physical function), three symptom scales, a global health status score, and six single items. Physical Function is assessed from 5 of the 30 questions (Questions 1-5), whose response score ranges on a 4 point scale. The score for physical function is calculated based on the average score from these 5 questions. A linear transformation is used to standardize these responses. Using this linear transformation, the minimum value is 0 (worst outcome, poor functionality) and the maximum value is 100 (best outcome, better functionality). Therefore, increasing values indicate better outcome and decreasing values indicate worse outcome.

Outcome measures

Outcome measures
Measure	Macrobead Implantation Arm n=41 Participants mCRC patients who will undergo up to 4 implantations of RENCA macrobeads (no less than 3 months apart), at a dosage level of 8 RENCA macrobeads per kilogram of body weight.	Implant 1: Day 14 n=39 Participants ECOG score at day 14 after first implantation	Implant 1: Day 30 n=36 Participants ECOG score at day 30 following first implantation	Implant 1: Day 60 n=26 Participants ECOG score at day 60 following first implantation	Implant 2: Day 0 n=8 Participants ECOG score at day 0 of second implantation	Implant 2: Day 14 n=8 Participants ECOG score at day 14 following second implantation	Implant 2: Day 30 n=7 Participants ECOG score at day 30 following second implantation	Implant 2: Day 60 n=6 Participants ECOG score at day 60 following second implantation
Physical Function	80.65 score on a scale Standard Deviation 17.94	69.57 score on a scale Standard Deviation 24.79	82.50 score on a scale Standard Deviation 12.96	83.50 score on a scale Standard Deviation 14.13	91.67 score on a scale Standard Deviation 9.26	90.00 score on a scale Standard Deviation 9.26	92.90 score on a scale Standard Deviation 4.88	90.00 score on a scale Standard Deviation 6.32

SECONDARY outcome

Timeframe: Baseline; Day 14, 30, 60 post-Implant 1; Day 14, 30, 60 post-Implant 2

Population: Analysis population was limited to the arm "macrobead implantation" as the proposed second arm "best supportive care" did not enroll enough participants to facilitate reliable analysis. Implant 1 (Day 0 to Day 60): Participants who had received at least 1 RENCA macrobead implantation; Implant 2 (Day 0 to Day 60): Participants who had received at least 2 RENCA macrobead implantations.

The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30, version 3.0) consists of 30 questions which pertain to: five functional scales (including role function), three symptom scales, a global health status score, and six single items. Role Function is assessed from 2 of the 30 questions (Questions 6 and 7), whose response score ranges on a 4 point scale. The score for role function is calculated based on the average score from these 2 questions. A linear transformation is used to standardize these responses. Using this linear transformation, the minimum value is 0 (worst outcome, poor functionality) and the maximum value is 100 (best outcome, better functionality). Therefore, increasing values indicate better outcome and decreasing values indicate worse outcome.

Outcome measures

Outcome measures
Measure	Macrobead Implantation Arm n=41 Participants mCRC patients who will undergo up to 4 implantations of RENCA macrobeads (no less than 3 months apart), at a dosage level of 8 RENCA macrobeads per kilogram of body weight.	Implant 1: Day 14 n=39 Participants ECOG score at day 14 after first implantation	Implant 1: Day 30 n=34 Participants ECOG score at day 30 following first implantation	Implant 1: Day 60 n=26 Participants ECOG score at day 60 following first implantation	Implant 2: Day 0 n=8 Participants ECOG score at day 0 of second implantation	Implant 2: Day 14 n=8 Participants ECOG score at day 14 following second implantation	Implant 2: Day 30 n=7 Participants ECOG score at day 30 following second implantation	Implant 2: Day 60 n=7 Participants ECOG score at day 60 following second implantation
Role Function	81.71 score on a scale Standard Deviation 20.00	55.56 score on a scale Standard Deviation 32.07	61.27 score on a scale Standard Deviation 32.75	74.36 score on a scale Standard Deviation 30.99	89.58 score on a scale Standard Deviation 15.27	60.42 score on a scale Standard Deviation 43.59	85.71 score on a scale Standard Deviation 20.25	95.24 score on a scale Standard Deviation 12.59

SECONDARY outcome

Timeframe: Baseline; Day 14, 30, 60 post-Implant 1; Day 14, 30, 60 post-Implant 2

Population: Analysis population was limited to the arm "macrobead implantation" as the proposed second arm "best supportive care" did not enroll enough participants to facilitate reliable analysis. Implant 1 (Day 0 to Day 60): Participants who had received at least 1 RENCA macrobead implantation; Implant 2 (Day 0 to Day 60): Participants who had received at least 2 RENCA macrobead implantations.

The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30, version 3.0) consists of 30 questions which pertain to: five functional scales (including emotional function), three symptom scales, a global health status score, and six single items. Emotional Function is assessed from 4 of the 30 questions (Questions 21-24), whose response score ranges on a 4 point scale. The score for role function is calculated based on the average score from these 4 questions. A linear transformation is used to standardize these responses. Using this linear transformation, the minimum value is 0 (worst outcome, poor functionality) and the maximum value is 100 (best outcome, better functionality). Therefore, increasing values indicate better outcome and decreasing values indicate worse outcome.

Outcome measures

Outcome measures
Measure	Macrobead Implantation Arm n=41 Participants mCRC patients who will undergo up to 4 implantations of RENCA macrobeads (no less than 3 months apart), at a dosage level of 8 RENCA macrobeads per kilogram of body weight.	Implant 1: Day 14 n=39 Participants ECOG score at day 14 after first implantation	Implant 1: Day 30 n=34 Participants ECOG score at day 30 following first implantation	Implant 1: Day 60 n=26 Participants ECOG score at day 60 following first implantation	Implant 2: Day 0 n=8 Participants ECOG score at day 0 of second implantation	Implant 2: Day 14 n=8 Participants ECOG score at day 14 following second implantation	Implant 2: Day 30 n=7 Participants ECOG score at day 30 following second implantation	Implant 2: Day 60 n=7 Participants ECOG score at day 60 following second implantation
Emotional Function	79.07 score on a scale Standard Deviation 22.06	72.65 score on a scale Standard Deviation 28.74	76.23 score on a scale Standard Deviation 27.91	80.56 score on a scale Standard Deviation 20.79	86.46 score on a scale Standard Deviation 11.73	78.13 score on a scale Standard Deviation 19.89	83.33 score on a scale Standard Deviation 19.84	88.10 score on a scale Standard Deviation 15.11

SECONDARY outcome

Timeframe: Baseline; Day 14, 30, 60 post-Implant 1; Day 14, 30, 60 post-Implant 2

Population: Analysis population was limited to the arm "macrobead implantation" as the proposed second arm "best supportive care" did not enroll enough participants to facilitate reliable analysis. Implant 1 (Day 0 to Day 60): Participants who had received at least 1 RENCA macrobead implantation; Implant 2 (Day 0 to Day 60): Participants who had received at least 2 RENCA macrobead implantations.

The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30, version 3.0) consists of 30 questions which pertain to: five functional scales (including cognitive function), three symptom scales, a global health status score, and six single items. Cognitive Function is assessed from 2 of the 30 questions (Question 20 and 25), whose response score ranges on a 4 point scale. The score for role function is calculated based on the average score from these 2 questions. A linear transformation is used to standardize these responses. Using this linear transformation, the minimum value is 0 (worst outcome, poor functionality) and the maximum value is 100 (best outcome, better functionality). Therefore, increasing values indicate better outcome and decreasing values indicate worse outcome.

Outcome measures

Outcome measures
Measure	Macrobead Implantation Arm n=41 Participants mCRC patients who will undergo up to 4 implantations of RENCA macrobeads (no less than 3 months apart), at a dosage level of 8 RENCA macrobeads per kilogram of body weight.	Implant 1: Day 14 n=39 Participants ECOG score at day 14 after first implantation	Implant 1: Day 30 n=34 Participants ECOG score at day 30 following first implantation	Implant 1: Day 60 n=26 Participants ECOG score at day 60 following first implantation	Implant 2: Day 0 n=8 Participants ECOG score at day 0 of second implantation	Implant 2: Day 14 n=8 Participants ECOG score at day 14 following second implantation	Implant 2: Day 30 n=7 Participants ECOG score at day 30 following second implantation	Implant 2: Day 60 n=7 Participants ECOG score at day 60 following second implantation
Cognitive Function	83.74 score on a scale Standard Deviation 16.02	83.76 score on a scale Standard Deviation 21.46	85.78 score on a scale Standard Deviation 15.43	86.54 score on a scale Standard Deviation 16.34	93.75 score on a scale Standard Deviation 12.40	90.15 score on a scale Standard Deviation 13.27	97.62 score on a scale Standard Deviation 6.29	95.24 score on a scale Standard Deviation 8.13

SECONDARY outcome

Timeframe: Baseline; Day 14, 30, 60 post-Implant 1; Day 14, 30, 60 post-Implant 2

Population: Analysis population was limited to the arm "macrobead implantation" as the proposed second arm "best supportive care" did not enroll enough participants to facilitate reliable analysis. Implant 1 (Day 0 to Day 60): Participants who had received at least 1 RENCA macrobead implantation; Implant 2 (Day 0 to Day 60): Participants who had received at least 2 RENCA macrobead implantations.

The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30, version 3.0) consists of 30 questions which pertain to: five functional scales (including social function), three symptom scales, a global health status score, and six single items. Social Function is assessed from 2 of the 30 questions (Question 26 and 27), whose response score ranges on a 4 point scale. The score for role function is calculated based on the average score from these 2 questions. A linear transformation is used to standardize these responses. Using this linear transformation, the minimum value is 0 (worst outcome, poor functionality) and the maximum value is 100 (best outcome, better functionality). Therefore, increasing values indicate better outcome and decreasing values indicate worse outcome.

Outcome measures

Outcome measures
Measure	Macrobead Implantation Arm n=41 Participants mCRC patients who will undergo up to 4 implantations of RENCA macrobeads (no less than 3 months apart), at a dosage level of 8 RENCA macrobeads per kilogram of body weight.	Implant 1: Day 14 n=39 Participants ECOG score at day 14 after first implantation	Implant 1: Day 30 n=34 Participants ECOG score at day 30 following first implantation	Implant 1: Day 60 n=26 Participants ECOG score at day 60 following first implantation	Implant 2: Day 0 n=8 Participants ECOG score at day 0 of second implantation	Implant 2: Day 14 n=8 Participants ECOG score at day 14 following second implantation	Implant 2: Day 30 n=7 Participants ECOG score at day 30 following second implantation	Implant 2: Day 60 n=7 Participants ECOG score at day 60 following second implantation
Social Function	76.83 score on a scale Standard Deviation 22.63	67.52 score on a scale Standard Deviation 33.21	69.61 score on a scale Standard Deviation 26.74	78.85 score on a scale Standard Deviation 26.89	93.75 score on a scale Standard Deviation 8.63	93.75 score on a scale Standard Deviation 12.40	88.10 score on a scale Standard Deviation 20.89	90.48 score on a scale Standard Deviation 13.11

SECONDARY outcome

Timeframe: Baseline; Day 14, 30, 60 post-Implant 1; Day 14, 30, 60 post-Implant 2

Population: Analysis population was limited to the arm "macrobead implantation" as the proposed second arm "best supportive care" did not enroll enough participants to facilitate reliable analysis. Implant 1 (Day 0 to Day 60): Participants who had received at least 1 RENCA macrobead implantation; Implant 2 (Day 0 to Day 60): Participants who had received at least 2 RENCA macrobead implantations.

Participants were asked to rate their pain on a discrete scale (from 0 = "no pain" to 100 "worst pain imaginable, unbearable"). The worst pain at each time point was used in the analysis.

Outcome measures

Outcome measures
Measure	Macrobead Implantation Arm n=41 Participants mCRC patients who will undergo up to 4 implantations of RENCA macrobeads (no less than 3 months apart), at a dosage level of 8 RENCA macrobeads per kilogram of body weight.	Implant 1: Day 14 n=39 Participants ECOG score at day 14 after first implantation	Implant 1: Day 30 n=34 Participants ECOG score at day 30 following first implantation	Implant 1: Day 60 n=26 Participants ECOG score at day 60 following first implantation	Implant 2: Day 0 n=8 Participants ECOG score at day 0 of second implantation	Implant 2: Day 14 n=8 Participants ECOG score at day 14 following second implantation	Implant 2: Day 30 n=7 Participants ECOG score at day 30 following second implantation	Implant 2: Day 60 n=7 Participants ECOG score at day 60 following second implantation
Pain Assessment	26.83 score on a scale Standard Deviation 26.58	52.56 score on a scale Standard Deviation 30.24	41.18 score on a scale Standard Deviation 30.22	33.33 score on a scale Standard Deviation 33.67	16.67 score on a scale Standard Deviation 19.92	22.92 score on a scale Standard Deviation 19.79	14.29 score on a scale Standard Deviation 20.25	14.29 score on a scale Standard Deviation 24.39

OTHER_PRE_SPECIFIED outcome

Timeframe: Change from baseline up to and including day 90 post-Implant 1.

Population: Participants receiving at least one RENCA macrobead implantation whose tumor marker response was greater than or equal to 20% decrease in one or both of CEA or CA 19-9.

Tumor markers included serum carcinoembryonic antigen (CEA) and cancer antigen 19-9 (CA 19-9), and were assessed on all participants in the RENCA macrobead implantation arm at baseline and at subsequent evaluation points to further assess tumor response to RENCA macrobead implantation. A tumor marker response was defined as a greater than or equal to 20% decrease in one or both of CEA or CA 19-9.

Outcome measures

Outcome measures
Measure	Macrobead Implantation Arm n=41 Participants mCRC patients who will undergo up to 4 implantations of RENCA macrobeads (no less than 3 months apart), at a dosage level of 8 RENCA macrobeads per kilogram of body weight.	Implant 1: Day 14 n=41 Participants ECOG score at day 14 after first implantation	Implant 1: Day 30 n=41 Participants ECOG score at day 30 following first implantation	Implant 1: Day 60 n=41 Participants ECOG score at day 60 following first implantation	Implant 2: Day 0 ECOG score at day 0 of second implantation	Implant 2: Day 14 ECOG score at day 14 following second implantation	Implant 2: Day 30 ECOG score at day 30 following second implantation	Implant 2: Day 60 ECOG score at day 60 following second implantation
Tumor Marker Response (CEA and CA 19-9)	6 Participants	5 Participants	12 Participants	18 Participants	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 30 months

Population: All participants who had received at least one implantation of RENCA macrobeads.

Overall survival (OS) of participants by tumor marker response. A responder is a participant having a decrease from baseline of 20% or more in CEA or CA 19-9 within 90 days of Implant. OS is the time interval between the date of radiographically documented disease progression and the date of death due to any cause. Participants still alive at the end of the study are censored at 22OCT2018.

Outcome measures

Outcome measures
Measure	Macrobead Implantation Arm n=23 Participants mCRC patients who will undergo up to 4 implantations of RENCA macrobeads (no less than 3 months apart), at a dosage level of 8 RENCA macrobeads per kilogram of body weight.	Implant 1: Day 14 n=18 Participants ECOG score at day 14 after first implantation	Implant 1: Day 30 ECOG score at day 30 following first implantation	Implant 1: Day 60 ECOG score at day 60 following first implantation	Implant 2: Day 0 ECOG score at day 0 of second implantation	Implant 2: Day 14 ECOG score at day 14 following second implantation	Implant 2: Day 30 ECOG score at day 30 following second implantation	Implant 2: Day 60 ECOG score at day 60 following second implantation
Overall Survival by Tumor Marker Response	10.33 months Interval 7.05 to 11.51	6.82 months Interval 3.54 to 14.98	—	—	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 90 post-Implant 1

Population: Participants who had received at least one macrobead implant and for whom baseline PET-CT scan and day 90 post-Implant 1 PET-CT scan data were available. n= 26 subjects; 77 lesions evaluated

Tumors were assessed by positron emission tomography (PET)-CT scan at baseline and day 90 following the first RENCA macrobead implantation. The use of \[13\]F-fluorodeoxyglucose (FDG) uptake for the detection of lesions \>1 cm in diameter allowed evaluation of metabolic activity. Decreases in FDG uptake were indicative of metabolic suppression of the tumor. The use of PET-CT scanning indicated anatomical localization, approximate size/volume of primary tumor and metastatic lesion(s), and assessment of metabolic activity of the tumor (as an indicator of metabolic health and necrosis). Disease state is reported as a function of Tumor measurement divided by SUVmax. Changes were assessed between day 90 post RENCA macrobead implant and baseline values. Patients with no change = stable; patients with decreased values = decreased/necrosis, and patients with increased values = increased.

Outcome measures

Outcome measures
Measure	Macrobead Implantation Arm n=77 lesions mCRC patients who will undergo up to 4 implantations of RENCA macrobeads (no less than 3 months apart), at a dosage level of 8 RENCA macrobeads per kilogram of body weight.	Implant 1: Day 14 n=77 lesions ECOG score at day 14 after first implantation	Implant 1: Day 30 n=77 lesions ECOG score at day 30 following first implantation	Implant 1: Day 60 ECOG score at day 60 following first implantation	Implant 2: Day 0 ECOG score at day 0 of second implantation	Implant 2: Day 14 ECOG score at day 14 following second implantation	Implant 2: Day 30 ECOG score at day 30 following second implantation	Implant 2: Day 60 ECOG score at day 60 following second implantation
Necrosis Comparison of Tumors Using PET-CT Scan	19 lesions	37 lesions	21 lesions	—	—	—	—	—

Adverse Events

Macrobead Implantation Arm

Serious events: 27 serious events

Other events: 41 other events

Deaths: 36 deaths

Serious adverse events

Serious adverse events
Measure	Macrobead Implantation Arm n=41 participants at risk Analysis population was limited to the arm "macrobead implantation" as the proposed second arm "best supportive care" did not enroll enough participants to facilitate reliable analysis. The arm reported here includes all patients who had at least one implantation of RENCA macrobeads.
Blood and lymphatic system disorders Anaemia	4.9% 2/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Blood and lymphatic system disorders Leukocytosis	2.4% 1/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Cardiac disorders Tachycardia	2.4% 1/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Gastrointestinal disorders Abdominal pain	17.1% 7/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Gastrointestinal disorders Nausea	7.3% 3/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Gastrointestinal disorders Vomiting	7.3% 3/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Gastrointestinal disorders Abdominal distension	4.9% 2/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Gastrointestinal disorders Ascites	2.4% 1/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Gastrointestinal disorders Large intestinal obstruction	2.4% 1/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Gastrointestinal disorders Small intestinal obstruction	2.4% 1/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
General disorders Disease progression	17.1% 7/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
General disorders Pyrexia	7.3% 3/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
General disorders Fatigue	2.4% 1/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
General disorders Malaise	2.4% 1/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
General disorders Pain	2.4% 1/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Infections and infestations Peritonitis	4.9% 2/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Infections and infestations Abdominal abscess	2.4% 1/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Infections and infestations Abdominal infection	2.4% 1/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Infections and infestations Empyema	2.4% 1/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Infections and infestations Influenza	2.4% 1/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Infections and infestations Pneumonia	2.4% 1/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Injury, poisoning and procedural complications Spinal column injury	2.4% 1/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Investigations Activated partial thromboplastin time prolonged	2.4% 1/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Investigations Blood biliriubin increased	2.4% 1/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Metabolism and nutrition disorders Dehydration	4.9% 2/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Metabolism and nutrition disorders Failure to thrive	2.4% 1/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Metabolism and nutrition disorders Hypokalaemia	2.4% 1/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	2.4% 1/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cerebellar tumour	2.4% 1/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Nervous system disorders Depressed level of consciousness	2.4% 1/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Nervous system disorders Dysarthria	2.4% 1/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Psychiatric disorders Mental status changes	2.4% 1/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Renal and urinary disorders Renal failure acute	2.4% 1/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Respiratory, thoracic and mediastinal disorders Pleural effusion	2.4% 1/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	2.4% 1/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.

Other adverse events

Other adverse events
Measure	Macrobead Implantation Arm n=41 participants at risk Analysis population was limited to the arm "macrobead implantation" as the proposed second arm "best supportive care" did not enroll enough participants to facilitate reliable analysis. The arm reported here includes all patients who had at least one implantation of RENCA macrobeads.
Nervous system disorders Disturbance in attention	4.9% 2/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Blood and lymphatic system disorders Anaemia	12.2% 5/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Gastrointestinal disorders Abdominal pain	36.6% 15/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Gastrointestinal disorders Nausea	36.6% 15/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Gastrointestinal disorders Constipation	34.1% 14/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Gastrointestinal disorders Diarrhoea	34.1% 14/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Gastrointestinal disorders Abdominal distension	26.8% 11/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Gastrointestinal disorders Vomiting	24.4% 10/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Gastrointestinal disorders Flatulence	9.8% 4/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Gastrointestinal disorders Abdominal pain, upper	7.3% 3/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Gastrointestinal disorders Ascites	4.9% 2/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Gastrointestinal disorders Proctalgia	7.3% 3/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
General disorders Fatigue	46.3% 19/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
General disorders Pyrexia	22.0% 9/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
General disorders Oedema peripheral	17.1% 7/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
General disorders Asthenia	12.2% 5/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
General disorders Chills	7.3% 3/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
General disorders Gait disturbance	7.3% 3/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Infections and infestations Urinary tract infection	7.3% 3/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Injury, poisoning and procedural complications Incision site pain	22.0% 9/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Investigations Weight decreased	14.6% 6/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Investigations Activated partial thromboplastin time prolonged	9.8% 4/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Investigations International normalised ratio increased	7.3% 3/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Metabolism and nutrition disorders Decreased appetite	41.5% 17/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Metabolism and nutrition disorders Dehydration	7.3% 3/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Metabolism and nutrition disorders Hyperglycaemia	12.2% 5/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Metabolism and nutrition disorders Hypoalbuminaemia	12.2% 5/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Gastrointestinal disorders Abdominal discomfort	4.9% 2/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Gastrointestinal disorders Abdominal pain, lower	4.9% 2/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Gastrointestinal disorders Dyspepsia	4.9% 2/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Injury, poisoning and procedural complications Contusion	4.9% 2/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Injury, poisoning and procedural complications Fall	4.9% 2/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Injury, poisoning and procedural complications Incision site complication	4.9% 2/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Investigations Blood alkaline phosphatase, increased	4.9% 2/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Investigations Blood creatinine, increased	4.9% 2/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Metabolism and nutrition disorders Hypokalaemia	4.9% 2/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Musculoskeletal and connective tissue disorders Back pain	17.1% 7/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	12.2% 5/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Musculoskeletal and connective tissue disorders Muscular weakness	7.3% 3/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Musculoskeletal and connective tissue disorders Arthralgia	4.9% 2/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Musculoskeletal and connective tissue disorders Flank Pain	4.9% 2/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Nervous system disorders Headache	12.2% 5/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Nervous system disorders Dizziness	9.8% 4/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Nervous system disorders Lethargy	7.3% 3/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Psychiatric disorders Insomnia	9.8% 4/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Psychiatric disorders Agitation	7.3% 3/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Psychiatric disorders Confusional state	7.3% 3/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Psychiatric disorders Anxiety	4.9% 2/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Psychiatric disorders Restlessness	4.9% 2/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Renal and urinary disorders Dysuria	4.9% 2/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Respiratory, thoracic and mediastinal disorders Dyspnoea	22.0% 9/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Respiratory, thoracic and mediastinal disorders Cough	12.2% 5/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	12.2% 5/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	7.3% 3/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Respiratory, thoracic and mediastinal disorders Pleural effusion	4.9% 2/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Respiratory, thoracic and mediastinal disorders Epistaxis	4.9% 2/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Respiratory, thoracic and mediastinal disorders Nasal congestion	4.9% 2/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	4.9% 2/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Respiratory, thoracic and mediastinal disorders Wheezing	4.9% 2/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Skin and subcutaneous tissue disorders Night sweats	9.8% 4/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Skin and subcutaneous tissue disorders Hyperhidrosis	7.3% 3/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Skin and subcutaneous tissue disorders Uticaria	4.9% 2/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.
Vascular disorders Deep vein thrombosis	4.9% 2/41 • From date of first macrobead implantation; assessed up to 32 months. The NCI CTCAE was used to standardize the terminology and grade the severity of reported adverse events. The Principal and Sub-Investigators, and the Attending Physicians, were responsible for monitoring adverse events and the safety of all participants. The Data Safety Monitoring Board, independently and in collaboration with the PIs, monitored and reviewed all safety findings, including study status, all SAEs, AEs \> Grade 2, laboratory values of special interest and all subject deaths.

Additional Information

Betty-Jane Sloan, Clinical Research Manager

The Rogosin Institute

Phone: 646-317-0701

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Sponsor retains the first right for scientific disclosure of study results. PI may draft a study results disclosure for scientific publication following the earlier of sponsor's disclosure or 12 months after study completion at all sites. Sponsor has 60 days to review PI's draft for patentable subject matter or confidential information. PI will delete any confidential information and delay any disclosure for another 60 days for sponsor to secure proprietary protection.
Publication restrictions are in place

Restriction type: OTHER