Trial Outcomes & Findings for Pilot Dose Escalation Trial of Stereotactic Body Radiation Therapy (SBRT) in Combination With GC4419 in Pancreatic Cancer (NCT NCT03340974)

Last Updated: 2023-12-15

Results Overview

Number of Common Terminology Criteria Adverse Events (CTCAE) that are grade 3 or 4 gastro-intestinal (GI) toxicities or deaths. CTCAE grade 3 or 4 gastro-intestinal toxicities are those adverse events that a subject may experience in their gastro-intestinal system that have been graded by the treating investigator to be severe (Grade 3) or life-threatening (Grade 4).

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

42 participants

Primary outcome timeframe

Within 90 days from the start of therapy "related" after CTCAE

Results posted on

2023-12-15

Participant Flow

Participant milestones

Participant milestones
Measure	GC4419 90 mg +50 Gy SBRT 90 mg Avasopasem manganese (GC4419) per day daily (60 min IV infusion, prior to SBRT), concurrent with daily fractions of SBRT (50 Gy)	GC4419 90 mg +55 Gy SBRT 90 mg Avasopasem manganese (GC4419) per day daily (60 min IV infusion, prior to SBRT), concurrent with daily fractions of SBRT (55 Gy)	Placebo + 50 Gy SBRT Placebo daily (60 min IV infusion, prior to SBRT), concurrent with daily fractions of SBRT (50 Gy)	Placebo +55 Gy SBRT Placebo daily (60 min IV infusion, prior to SBRT), concurrent with daily fractions of SBRT (55 Gy)
Active Protocol Treatment STARTED	18	6	6	12
Active Protocol Treatment COMPLETED	18	6	6	12
Active Protocol Treatment NOT COMPLETED	0	0	0	0
Completion of Study -Long Term Follow up STARTED	18	6	6	12
Completion of Study -Long Term Follow up COMPLETED	0	0	0	0
Completion of Study -Long Term Follow up NOT COMPLETED	18	6	6	12

Reasons for withdrawal

Reasons for withdrawal
Measure	GC4419 90 mg +50 Gy SBRT 90 mg Avasopasem manganese (GC4419) per day daily (60 min IV infusion, prior to SBRT), concurrent with daily fractions of SBRT (50 Gy)	GC4419 90 mg +55 Gy SBRT 90 mg Avasopasem manganese (GC4419) per day daily (60 min IV infusion, prior to SBRT), concurrent with daily fractions of SBRT (55 Gy)	Placebo + 50 Gy SBRT Placebo daily (60 min IV infusion, prior to SBRT), concurrent with daily fractions of SBRT (50 Gy)	Placebo +55 Gy SBRT Placebo daily (60 min IV infusion, prior to SBRT), concurrent with daily fractions of SBRT (55 Gy)
Completion of Study -Long Term Follow up Death	8	5	5	7
Completion of Study -Long Term Follow up Withdrawal by Subject	2	0	0	1
Completion of Study -Long Term Follow up Lost to Follow-up	0	1	1	2
Completion of Study -Long Term Follow up Last Know Alive	8	0	0	2

Baseline Characteristics

Pilot Dose Escalation Trial of Stereotactic Body Radiation Therapy (SBRT) in Combination With GC4419 in Pancreatic Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	GC4419 90 mg +50 Gy n=18 Participants Avasopasem (GC4419) + SBRT GC4419: 90 mg Avasopasem (GC4419) per day daily (60 min IV infusion, prior to SBRT), concurrent with daily fractions of SBRT to assigned dose level	GC4419 90mg +55 Gy n=6 Participants Avasopasem (GC4419) + SBRT GC4419: 90 mg Avasopasem (GC4419) per day daily (60 min IV infusion, prior to SBRT), concurrent with daily fractions of SBRT to assigned dose level	Placebo +50 Gy n=6 Participants Placebo +SBRT Placebo: Placebo daily (60 min IV infusion, prior to SBRT), concurrent with daily fractions of SBRT to assigned dose level	Placebo +55 Gy n=12 Participants Placebo +SBRT Placebo: Placebo daily (60 min IV infusion, prior to SBRT), concurrent with daily fractions of SBRT to assigned dose level	Total n=42 Participants Total of all reporting groups
Age, Customized Age group (years) · Age Group 18-65 years	4 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	4 Participants n=4 Participants	13 Participants n=21 Participants
Age, Customized Age group (years) · Age Group 66-75	8 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	8 Participants n=4 Participants	20 Participants n=21 Participants
Age, Customized Age group (years) · Age Group >75	6 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	0 Participants n=4 Participants	9 Participants n=21 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants	6 Participants n=4 Participants	19 Participants n=21 Participants
Sex: Female, Male Male	13 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	6 Participants n=4 Participants	23 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants	5 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	14 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants	9 Participants n=4 Participants	35 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	2 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	0 Participants n=4 Participants	3 Participants n=21 Participants
Race (NIH/OMB) White	16 Participants n=5 Participants	5 Participants n=7 Participants	4 Participants n=5 Participants	12 Participants n=4 Participants	37 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants
Region of Enrollment United States	18 participants n=5 Participants	6 participants n=7 Participants	6 participants n=5 Participants	12 participants n=4 Participants	42 participants n=21 Participants

PRIMARY outcome

Timeframe: Within 90 days from the start of therapy "related" after CTCAE

Population: Intent-to-Treat (ITT) population, which consisted of all randomized subjects who received at least 1 dose of GC4419/placebo and/or SBRT. The ITT population excluded randomization failures (ie, randomized subjects who did not receive any GC4419/placebo or SBRT).

Outcome measures

Outcome measures
Measure	GC4419 90 mg + 50 Gy n=18 Participants SBRT + Avasopasem (GC4419) GC4419: 90 mg Avasopasem (GC4419) per day daily (60 min IV infusion, prior to SBRT), concurrent with daily fractions of SBRT .	GC4419 90 mg +55 Gy n=6 Participants SBRT + Placebo Placebo: Placebo daily (60 min IV infusion, prior to SBRT), concurrent with daily fractions of SBRT to assigned dose level	Placebo + 50 Gy SBRT n=6 Participants Placebo daily (60 min IV infusion, prior to SBRT), concurrent with daily fractions of SBRT (50 Gy)	Placebo +55 Gy SBRT n=12 Participants Placebo daily (60 min IV infusion, prior to SBRT), concurrent with daily fractions of SBRT (55 Gy)
CTCAE Grade 3 or 4 Gastro-intestinal (GI) Toxicities or Death Within 90 Days From the Start of Therapy Deaths within 90 days from last dose of study treatment	1 Events	0 Events	0 Events	0 Events
CTCAE Grade 3 or 4 Gastro-intestinal (GI) Toxicities or Death Within 90 Days From the Start of Therapy Grade 3 or 4 Gastrointestinal Toxicities	1 Events	1 Events	0 Events	1 Events

PRIMARY outcome

Timeframe: All subjects assessed with at least 12 months of follow up following the administration of SBRT

Population: Intent-to-Treat (ITT) population which consisted of all randomized subjects who received at least 1 dose of avasopasem/placebo and/or SBRT with the most restrictive censoring scenario ( subjects censored at the time of surgery, new anti-cancer therapy, and new malignancy)

Per Response Evaluation Criteria In Solid Tumors (RECIST) criteria for target lesions that are assessed by radiographic imaging : Complete Response (CR) is the disappearance of all target lesions; Partial Response (PR) is at least a 30% decrease in the longest diameter of the target lesions; Stable disease (SD) is neither sufficient shrinkage to qualify for a PR nor sufficient increase to qualify for local progressive disease (LPD); Local Progressive Disease (LPD) is at least a 20% increase in the longest diameter of the target lesion, utilizing the baseline measurement as reference.

Outcome measures

Outcome measures
Measure	GC4419 90 mg + 50 Gy n=18 Participants SBRT + Avasopasem (GC4419) GC4419: 90 mg Avasopasem (GC4419) per day daily (60 min IV infusion, prior to SBRT), concurrent with daily fractions of SBRT .	GC4419 90 mg +55 Gy n=6 Participants SBRT + Placebo Placebo: Placebo daily (60 min IV infusion, prior to SBRT), concurrent with daily fractions of SBRT to assigned dose level	Placebo + 50 Gy SBRT n=6 Participants Placebo daily (60 min IV infusion, prior to SBRT), concurrent with daily fractions of SBRT (50 Gy)	Placebo +55 Gy SBRT n=12 Participants Placebo daily (60 min IV infusion, prior to SBRT), concurrent with daily fractions of SBRT (55 Gy)
Radiographic Stable Disease (SD) or Better Based on RECIST Criteria Stable Disease	12 Participants	3 Participants	5 Participants	8 Participants
Radiographic Stable Disease (SD) or Better Based on RECIST Criteria Partial Response	4 Participants	3 Participants	1 Participants	1 Participants
Radiographic Stable Disease (SD) or Better Based on RECIST Criteria Progressive Disease	0 Participants	0 Participants	0 Participants	1 Participants
Radiographic Stable Disease (SD) or Better Based on RECIST Criteria Not Evaluated/Censored	2 Participants	0 Participants	0 Participants	2 Participants

Adverse Events

GC4419 90 mg +50 Gy

Serious events: 7 serious events

Other events: 9 other events

Deaths: 8 deaths

GC4419 90mg +55 Gy

Serious events: 1 serious events

Other events: 5 other events

Deaths: 5 deaths

Placebo +50 Gy

Serious events: 0 serious events

Other events: 6 other events

Deaths: 5 deaths

Placebo +55 Gy

Serious events: 4 serious events

Other events: 7 other events

Deaths: 7 deaths

Serious adverse events

Serious adverse events
Measure	GC4419 90 mg +50 Gy n=18 participants at risk Avasopasem (GC4419) + SBRT GC4419: 90 mg Avasopasem (GC4419) per day daily (60 min IV infusion, prior to SBRT), concurrent with daily fractions of SBRT to assigned dose level	GC4419 90mg +55 Gy n=6 participants at risk Avasopasem (GC4419) + SBRT GC4419: 90 mg Avasopasem (GC4419) per day daily (60 min IV infusion, prior to SBRT), concurrent with daily fractions of SBRT to assigned dose level	Placebo +50 Gy n=6 participants at risk Placebo +SBRT Placebo: Placebo daily (60 min IV infusion, prior to SBRT), concurrent with daily fractions of SBRT to assigned dose level	Placebo +55 Gy n=12 participants at risk Placebo +SBRT Placebo: Placebo daily (60 min IV infusion, prior to SBRT), concurrent with daily fractions of SBRT to assigned dose level
Gastrointestinal disorders Abdominal Pain	0.00% 0/18 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	0.00% 0/6 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	0.00% 0/6 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	8.3% 1/12 • Number of events 1 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)
Gastrointestinal disorders Colitis	0.00% 0/18 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	16.7% 1/6 • Number of events 1 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	0.00% 0/6 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	0.00% 0/12 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)
Gastrointestinal disorders Obstruction gastric	5.6% 1/18 • Number of events 1 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	0.00% 0/6 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	0.00% 0/6 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	0.00% 0/12 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)
Infections and infestations Abdominal Abscess	5.6% 1/18 • Number of events 1 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	0.00% 0/6 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	0.00% 0/6 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	0.00% 0/12 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)
Infections and infestations Lung Infection	5.6% 1/18 • Number of events 1 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	0.00% 0/6 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	0.00% 0/6 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	0.00% 0/12 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)
Cardiac disorders Atrial Fibrillation	5.6% 1/18 • Number of events 1 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	0.00% 0/6 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	0.00% 0/6 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	0.00% 0/12 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)
Gastrointestinal disorders Pyrexia	0.00% 0/18 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	0.00% 0/6 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	0.00% 0/6 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	8.3% 1/12 • Number of events 1 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)
Hepatobiliary disorders Cholangitis acute	0.00% 0/18 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	0.00% 0/6 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	0.00% 0/6 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	8.3% 1/12 • Number of events 1 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)
Investigations Blood lactic acid increased	0.00% 0/18 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	0.00% 0/6 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	0.00% 0/6 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	8.3% 1/12 • Number of events 1 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)
Renal and urinary disorders Acute kidney injury	5.6% 1/18 • Number of events 1 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	0.00% 0/6 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	0.00% 0/6 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	0.00% 0/12 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)
Respiratory, thoracic and mediastinal disorders Respiratory Failure	5.6% 1/18 • Number of events 1 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	0.00% 0/6 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	0.00% 0/6 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	0.00% 0/12 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)
Vascular disorders Haematoma	5.6% 1/18 • Number of events 1 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	0.00% 0/6 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	0.00% 0/6 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	0.00% 0/12 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)

Other adverse events

Additional Information

Judy Schnyder, Sr. Vice President Clinical Operations and Data Management

Galera Therapeutics

Phone: 484-870-9625

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee A copy of the proposed study manuscript for publication, presentation or other disclosure must first be forwarded to Sponsor not less than 30 days prior to submission for review and comment. PI agrees to delete or revise references to confidential information upon Sponsor's request and PI agrees to to consider all other comments of Sponsor in good faith.
Publication restrictions are in place

Restriction type: OTHER

Measure	GC4419 90 mg +50 Gy n=18 participants at risk Avasopasem (GC4419) + SBRT GC4419: 90 mg Avasopasem (GC4419) per day daily (60 min IV infusion, prior to SBRT), concurrent with daily fractions of SBRT to assigned dose level	GC4419 90mg +55 Gy n=6 participants at risk Avasopasem (GC4419) + SBRT GC4419: 90 mg Avasopasem (GC4419) per day daily (60 min IV infusion, prior to SBRT), concurrent with daily fractions of SBRT to assigned dose level	Placebo +50 Gy n=6 participants at risk Placebo +SBRT Placebo: Placebo daily (60 min IV infusion, prior to SBRT), concurrent with daily fractions of SBRT to assigned dose level	Placebo +55 Gy n=12 participants at risk Placebo +SBRT Placebo: Placebo daily (60 min IV infusion, prior to SBRT), concurrent with daily fractions of SBRT to assigned dose level
Gastrointestinal disorders Nausea	33.3% 6/18 • Number of events 7 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	83.3% 5/6 • Number of events 5 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	66.7% 4/6 • Number of events 7 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	25.0% 3/12 • Number of events 3 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)
Gastrointestinal disorders Diarrhoea	27.8% 5/18 • Number of events 7 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	16.7% 1/6 • Number of events 1 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	50.0% 3/6 • Number of events 3 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	25.0% 3/12 • Number of events 4 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)
Gastrointestinal disorders Vomiting	16.7% 3/18 • Number of events 5 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	50.0% 3/6 • Number of events 3 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	16.7% 1/6 • Number of events 1 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	16.7% 2/12 • Number of events 2 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)
Investigations Blood alkaline phosphatase increase	11.1% 2/18 • Number of events 5 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	16.7% 1/6 • Number of events 1 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	33.3% 2/6 • Number of events 2 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	8.3% 1/12 • Number of events 1 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)
General disorders Fatigue	16.7% 3/18 • Number of events 4 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	50.0% 3/6 • Number of events 5 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	83.3% 5/6 • Number of events 7 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	25.0% 3/12 • Number of events 3 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)
Gastrointestinal disorders Abdominal Pain	22.2% 4/18 • Number of events 4 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	16.7% 1/6 • Number of events 1 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	66.7% 4/6 • Number of events 4 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	8.3% 1/12 • Number of events 1 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)
Investigations Alanine aminotransferase increased	16.7% 3/18 • Number of events 4 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	0.00% 0/6 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	0.00% 0/6 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	8.3% 1/12 • Number of events 1 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)
Investigations Aspartate aminotransferase increase	11.1% 2/18 • Number of events 3 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	0.00% 0/6 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	0.00% 0/6 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	0.00% 0/12 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)
General disorders Hypoaesthesia	5.6% 1/18 • Number of events 3 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	0.00% 0/6 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	0.00% 0/6 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	0.00% 0/12 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)
Blood and lymphatic system disorders Anemia	11.1% 2/18 • Number of events 2 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	33.3% 2/6 • Number of events 3 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	33.3% 2/6 • Number of events 3 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	16.7% 2/12 • Number of events 2 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)
Gastrointestinal disorders Constipation	11.1% 2/18 • Number of events 2 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	50.0% 3/6 • Number of events 3 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	0.00% 0/6 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	16.7% 2/12 • Number of events 2 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)
Gastrointestinal disorders Erucation	11.1% 2/18 • Number of events 2 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	16.7% 1/6 • Number of events 1 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	0.00% 0/6 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	0.00% 0/12 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)
Blood and lymphatic system disorders Thrombocytopenia	5.6% 1/18 • Number of events 1 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	33.3% 2/6 • Number of events 2 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	33.3% 2/6 • Number of events 3 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	33.3% 4/12 • Number of events 4 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)
General disorders Pain	5.6% 1/18 • Number of events 1 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	33.3% 2/6 • Number of events 2 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	16.7% 1/6 • Number of events 1 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	0.00% 0/12 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)
Metabolism and nutrition disorders Decreased Appetite	5.6% 1/18 • Number of events 1 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	33.3% 2/6 • Number of events 2 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	0.00% 0/6 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	0.00% 0/12 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)
Musculoskeletal and connective tissue disorders Musculoskeletal Pain	5.6% 1/18 • Number of events 1 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	0.00% 0/6 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	16.7% 1/6 • Number of events 2 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	0.00% 0/12 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)
Blood and lymphatic system disorders Leukopenia	0.00% 0/18 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	50.0% 3/6 • Number of events 5 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	33.3% 2/6 • Number of events 4 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	0.00% 0/12 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)
Cardiac disorders Hypertension	0.00% 0/18 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	16.7% 1/6 • Number of events 4 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	0.00% 0/6 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	0.00% 0/12 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)
Blood and lymphatic system disorders Neutropenia	0.00% 0/18 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	33.3% 2/6 • Number of events 2 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	0.00% 0/6 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	0.00% 0/12 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)
General disorders Pyrexia	0.00% 0/18 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	16.7% 1/6 • Number of events 1 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	33.3% 2/6 • Number of events 2 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	0.00% 0/12 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)
Blood and lymphatic system disorders Lymphopenia	0.00% 0/18 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	0.00% 0/6 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	16.7% 1/6 • Number of events 3 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	16.7% 2/12 • Number of events 2 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)
Musculoskeletal and connective tissue disorders Back Pain	0.00% 0/18 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	0.00% 0/6 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	16.7% 1/6 • Number of events 2 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	8.3% 1/12 • Number of events 1 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)
Nervous system disorders Dizziness	0.00% 0/18 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	0.00% 0/6 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	33.3% 2/6 • Number of events 2 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)	0.00% 0/12 • Adverse events were collected from the date of subject randomization until 12 months following the last dose of SBRT (total duration approximately 14 months)