Trial Outcomes & Findings for Safety, Efficacy, and Dosing of Stereotactic Radiosurgery for Hepato-cellular Carc/Colo-rectal Liver Metastases (NCT NCT01528878)
NCT ID: NCT01528878
Last Updated: 2018-07-26
Results Overview
To determine a tolerable dose, cumulative acute toxicity was collected (defined as toxicity occurring within 90 days of treatment initiation). Adverse events were graded by the Common Terminology Criteria for Adverse Events version 3.0. Tolerability was based on hepatic toxicity. A grading (severity) scale is provided for each adverse event (AE) term. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE.
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
30 participants
Primary outcome timeframe
90 days
Results posted on
2018-07-26
Participant Flow
Patients were enrolled from June, 2009 to March, 2014 at two institutions.
39 participants were consented and 9 were found ineligible and were not treated.
Participant milestones
| Measure |
Single Arm Patients With HCC or Liver Metastases
Patients with hepatocellular carcinoma (HCC) who are not appropriate for surgical resection or radiofrequency ablation (RFA) as a bridge to transplant. The original cohort was not analyzed between good vs compromised liver function because there were only 2 patients with Child-Pugh Class B and secondary outcomes measured are thought to be more influenced by disease rather than liver function (which may be more relevant for toxicity).
|
|---|---|
|
Overall Study
STARTED
|
30
|
|
Overall Study
COMPLETED
|
30
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Safety, Efficacy, and Dosing of Stereotactic Radiosurgery for Hepato-cellular Carc/Colo-rectal Liver Metastases
Baseline characteristics by cohort
| Measure |
Single Arm Patients With HCC or Liver Metastases
n=30 Participants
Patients with hepatocellular carcinoma (HCC) who are not appropriate for surgical resection or radiofrequency ablation (RFA) as a bridge to transplant. The original cohort was not analyzed between good vs compromised liver function because there were only 2 patients with Child-Pugh Class B and secondary outcomes measured are thought to be more influenced by disease rather than liver function (which may be more relevant for toxicity).
|
|---|---|
|
Age, Continuous
|
65.5 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
11 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
19 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
9 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
18 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
30 Participants
n=5 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status
0
|
17 Participants
n=5 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status
1
|
13 Participants
n=5 Participants
|
|
Child Pugh Score
5 (Class A)
|
22 Participants
n=5 Participants
|
|
Child Pugh Score
6 (Class A)
|
6 Participants
n=5 Participants
|
|
Child Pugh Score
>=7 (Class B)
|
2 Participants
n=5 Participants
|
|
Primary Disease
Hepatocellular carcinoma
|
11 Participants
n=5 Participants
|
|
Primary Disease
Metastatic cancer
|
19 Participants
n=5 Participants
|
|
Prior liver-directed therapies
Any local therapy
|
14 Participants
n=5 Participants
|
|
Prior liver-directed therapies
Liver resection
|
9 Participants
n=5 Participants
|
|
Prior liver-directed therapies
Trans-arterial chemoembolization (TACE)
|
7 Participants
n=5 Participants
|
|
Prior liver-directed therapies
Radiofrequency ablation (RFA)
|
6 Participants
n=5 Participants
|
|
Prior liver-directed therapies
> 1 prior local therapy
|
9 Participants
n=5 Participants
|
|
Prior liver-directed therapies
Resection + RFA
|
3 Participants
n=5 Participants
|
|
Prior liver-directed therapies
Resection + TACE
|
2 Participants
n=5 Participants
|
|
Prior liver-directed therapies
Resection x2 + RFA
|
1 Participants
n=5 Participants
|
|
Prior liver-directed therapies
TACE + RFA x3
|
1 Participants
n=5 Participants
|
|
Prior liver-directed therapies
TACE x 2 + RFA
|
1 Participants
n=5 Participants
|
|
Prior liver-directed therapies
TACE x 2
|
1 Participants
n=5 Participants
|
|
Prior systemic therapy
|
16 Participants
n=5 Participants
|
|
Number of lesions treated
1
|
26 Participants
n=5 Participants
|
|
Number of lesions treated
2
|
3 Participants
n=5 Participants
|
|
Number of lesions treated
3
|
1 Participants
n=5 Participants
|
|
Lesion size (cm)
<2
|
1 Participants
n=5 Participants
|
|
Lesion size (cm)
2-2.9
|
10 Participants
n=5 Participants
|
|
Lesion size (cm)
3-3.9
|
9 Participants
n=5 Participants
|
|
Lesion size (cm)
4-4.9
|
2 Participants
n=5 Participants
|
|
Lesion size (cm)
5-5.9
|
5 Participants
n=5 Participants
|
|
Lesion size (cm)
>6
|
3 Participants
n=5 Participants
|
|
Lesion size (cm) median (range)
|
3.5 cm
n=5 Participants
|
|
Gross tumor volume (cc) median (range)
|
22.5 cc
n=5 Participants
|
|
Planning target volume (cc) median (range)
|
65.5 cc
n=5 Participants
|
|
Fractionation
5.5 Gy x 5 = 27.5 Gy
|
1 Participants
n=5 Participants
|
|
Fractionation
7 Gy x 5 = 35 Gy
|
2 Participants
n=5 Participants
|
|
Fractionation
10 Gy x 3 = 30 Gy
|
1 Participants
n=5 Participants
|
|
Fractionation
12.5 Gy x 3 = 37.5 Gy
|
4 Participants
n=5 Participants
|
|
Fractionation
13.33 Gy x 3 = 40 Gy
|
1 Participants
n=5 Participants
|
|
Fractionation
15 Gy x 3 = 45 Gy
|
21 Participants
n=5 Participants
|
|
Dose of Radiation Therapy (Gy)
|
45 Gray (Gy)
n=5 Participants
|
|
Mean liver dose (Gy) )
|
10.3 Gy
n=5 Participants
|
|
Volume of liver receiving <15 Gy (cc)
|
1239 cc
n=5 Participants
|
PRIMARY outcome
Timeframe: 90 daysTo determine a tolerable dose, cumulative acute toxicity was collected (defined as toxicity occurring within 90 days of treatment initiation). Adverse events were graded by the Common Terminology Criteria for Adverse Events version 3.0. Tolerability was based on hepatic toxicity. A grading (severity) scale is provided for each adverse event (AE) term. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE.
Outcome measures
| Measure |
Grade 2 Adverse Events
n=30 Participants
Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL)
|
Grade 3 Adverse Events
n=30 Participants
Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL.
|
|---|---|---|
|
Tolerability of Stereotactic Body Radiotherapy (SBRT) Based on Number of Cumulative Acute Toxicities Occurring Within 90 Days of Treatment and Related to SBRT.
Elevated Aspartate Aminotransferase
|
5 Participants
|
1 Participants
|
|
Tolerability of Stereotactic Body Radiotherapy (SBRT) Based on Number of Cumulative Acute Toxicities Occurring Within 90 Days of Treatment and Related to SBRT.
Elevated Bilirubin
|
4 Participants
|
0 Participants
|
|
Tolerability of Stereotactic Body Radiotherapy (SBRT) Based on Number of Cumulative Acute Toxicities Occurring Within 90 Days of Treatment and Related to SBRT.
Low Hemoglobin
|
4 Participants
|
0 Participants
|
|
Tolerability of Stereotactic Body Radiotherapy (SBRT) Based on Number of Cumulative Acute Toxicities Occurring Within 90 Days of Treatment and Related to SBRT.
Fatigue
|
4 Participants
|
0 Participants
|
|
Tolerability of Stereotactic Body Radiotherapy (SBRT) Based on Number of Cumulative Acute Toxicities Occurring Within 90 Days of Treatment and Related to SBRT.
Increased Alanine Aminotransferase
|
3 Participants
|
0 Participants
|
|
Tolerability of Stereotactic Body Radiotherapy (SBRT) Based on Number of Cumulative Acute Toxicities Occurring Within 90 Days of Treatment and Related to SBRT.
Decreased Leukocyte
|
2 Participants
|
1 Participants
|
|
Tolerability of Stereotactic Body Radiotherapy (SBRT) Based on Number of Cumulative Acute Toxicities Occurring Within 90 Days of Treatment and Related to SBRT.
Nausea
|
2 Participants
|
0 Participants
|
|
Tolerability of Stereotactic Body Radiotherapy (SBRT) Based on Number of Cumulative Acute Toxicities Occurring Within 90 Days of Treatment and Related to SBRT.
Abdominal pain
|
2 Participants
|
0 Participants
|
|
Tolerability of Stereotactic Body Radiotherapy (SBRT) Based on Number of Cumulative Acute Toxicities Occurring Within 90 Days of Treatment and Related to SBRT.
Increased alkaline phosphatase
|
2 Participants
|
0 Participants
|
|
Tolerability of Stereotactic Body Radiotherapy (SBRT) Based on Number of Cumulative Acute Toxicities Occurring Within 90 Days of Treatment and Related to SBRT.
international normalized ratio increased
|
2 Participants
|
0 Participants
|
|
Tolerability of Stereotactic Body Radiotherapy (SBRT) Based on Number of Cumulative Acute Toxicities Occurring Within 90 Days of Treatment and Related to SBRT.
Decreased Platelets
|
2 Participants
|
0 Participants
|
|
Tolerability of Stereotactic Body Radiotherapy (SBRT) Based on Number of Cumulative Acute Toxicities Occurring Within 90 Days of Treatment and Related to SBRT.
Dyspnea
|
1 Participants
|
0 Participants
|
|
Tolerability of Stereotactic Body Radiotherapy (SBRT) Based on Number of Cumulative Acute Toxicities Occurring Within 90 Days of Treatment and Related to SBRT.
Acute total
|
14 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: 12.7 months1 year local control defined as percentage of patients with freedom from local progression at a median follow-up time of 12.7 months. Progressive disease is defined as increase by \>= 50% of product of the two perpendicular diameters of an irradiated lesion.
Outcome measures
| Measure |
Grade 2 Adverse Events
n=30 Participants
Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL)
|
Grade 3 Adverse Events
Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL.
|
|---|---|---|
|
Local Tumor Control to Doses of Radiation in Patients With Liver Cancer or Metastases to the Liver
|
81 percentage of participants
|
—
|
SECONDARY outcome
Timeframe: 6 monthsComplete response (CR) is defined as disappearance of the target lesion, partial response (PR) as regression of measureable disease, progressive disease (PD) as increase by \>= 50% in product of the two perpendicular diameters of an irradiated lesion, and stable disease (SD) as all others not meeting criteria for CR, PR, or PD.
Outcome measures
| Measure |
Grade 2 Adverse Events
n=30 Participants
Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL)
|
Grade 3 Adverse Events
Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL.
|
|---|---|---|
|
Percentage of Local Response to Doses of Radiation in Patients With Liver Cancer or Metastases to the Liver
Complete Response
|
7 percentage of participants
|
—
|
|
Percentage of Local Response to Doses of Radiation in Patients With Liver Cancer or Metastases to the Liver
Partial Response
|
13 percentage of participants
|
—
|
|
Percentage of Local Response to Doses of Radiation in Patients With Liver Cancer or Metastases to the Liver
Stable Disease
|
80 percentage of participants
|
—
|
SECONDARY outcome
Timeframe: 1 yearOverall survival is defined as percentage of patients remaining alive from start of study treatment to 1 year.
Outcome measures
| Measure |
Grade 2 Adverse Events
n=30 Participants
Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL)
|
Grade 3 Adverse Events
Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL.
|
|---|---|---|
|
Overall Survival of Patients With Liver Cancer or Metastases to the Liver
|
62 percentage of participants
|
—
|
Adverse Events
Single Arm Patients With HCC or Liver Metastases
Serious events: 1 serious events
Other events: 27 other events
Deaths: 15 deaths
Serious adverse events
| Measure |
Single Arm Patients With HCC or Liver Metastases
n=30 participants at risk
Patients with hepatocellular carcinoma (HCC) who are not appropriate for surgical resection or radiofrequency ablation (RFA) as a bridge to transplant. The original cohort was not analyzed between good vs compromised liver function because there were only 2 patients with Child-Pugh Class B and secondary outcomes measured are thought to be more influenced by disease rather than liver function (which may be more relevant for toxicity).
|
|---|---|
|
Musculoskeletal and connective tissue disorders
Pain- chest wall
|
3.3%
1/30 • 44 weeks
|
Other adverse events
| Measure |
Single Arm Patients With HCC or Liver Metastases
n=30 participants at risk
Patients with hepatocellular carcinoma (HCC) who are not appropriate for surgical resection or radiofrequency ablation (RFA) as a bridge to transplant. The original cohort was not analyzed between good vs compromised liver function because there were only 2 patients with Child-Pugh Class B and secondary outcomes measured are thought to be more influenced by disease rather than liver function (which may be more relevant for toxicity).
|
|---|---|
|
Metabolism and nutrition disorders
Albumin, serum-low (hypoalbuminemia)
|
23.3%
7/30 • 44 weeks
|
|
Investigations
Alkaline phosphatase
|
43.3%
13/30 • 44 weeks
|
|
Investigations
ALT, SGPT (serum glutamic pyruvic transaminase)
|
30.0%
9/30 • 44 weeks
|
|
Investigations
AST, SGOT(serum glutamic oxaloacetic transaminase)
|
46.7%
14/30 • 44 weeks
|
|
Investigations
Bilirubin (hyperbilirubinemia)
|
23.3%
7/30 • 44 weeks
|
|
Psychiatric disorders
Confusion
|
6.7%
2/30 • 44 weeks
|
|
Gastrointestinal disorders
Constipation
|
10.0%
3/30 • 44 weeks
|
|
Gastrointestinal disorders
Diarrhea
|
10.0%
3/30 • 44 weeks
|
|
Nervous system disorders
Dizziness
|
10.0%
3/30 • 44 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)
|
6.7%
2/30 • 44 weeks
|
|
General disorders
Edema: limb
|
6.7%
2/30 • 44 weeks
|
|
General disorders
Fatigue (asthenia, lethargy, malaise)
|
53.3%
16/30 • 44 weeks
|
|
Investigations
GGT (gamma-Glutamyl transpeptidase)
|
6.7%
2/30 • 44 weeks
|
|
Metabolism and nutrition disorders
Glucose, serum-high (hyperglycemia)
|
13.3%
4/30 • 44 weeks
|
|
Blood and lymphatic system disorders
Hemoglobin
|
23.3%
7/30 • 44 weeks
|
|
Investigations
INR (International Normalized Ratio of prothrombin time)
|
10.0%
3/30 • 44 weeks
|
|
Investigations
Leukocytes (total WBC)
|
23.3%
7/30 • 44 weeks
|
|
Investigations
Lymphopenia
|
46.7%
14/30 • 44 weeks
|
|
Psychiatric disorders
Mood alteration - Anxiety
|
6.7%
2/30 • 44 weeks
|
|
Gastrointestinal disorders
Nausea
|
16.7%
5/30 • 44 weeks
|
|
Investigations
Neutrophils/granulocytes (ANC/AGC)
|
13.3%
4/30 • 44 weeks
|
|
Gastrointestinal disorders
Pain - Abdomen NOS
|
23.3%
7/30 • 44 weeks
|
|
Musculoskeletal and connective tissue disorders
Pain - Back
|
13.3%
4/30 • 44 weeks
|
|
Musculoskeletal and connective tissue disorders
Pain - Chest wall
|
10.0%
3/30 • 44 weeks
|
|
Musculoskeletal and connective tissue disorders
Pain - Extremity-limb
|
6.7%
2/30 • 44 weeks
|
|
Investigations
Platelets
|
36.7%
11/30 • 44 weeks
|
|
Metabolism and nutrition disorders
Sodium, serum-low (hyponatremia)
|
6.7%
2/30 • 44 weeks
|
Additional Information
Robin Johnson
UNC Lineberger Comprehensive Cancer Center
Phone: 919-966-1125
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60