Trial Outcomes & Findings for A Randomized Trial Evaluating Rapid Delivery of Dose Escalated Hypofractionated Radiotherapy for Patients Diagnosed With Bone Metastases for Effective Palliation of Symptoms (NCT NCT02163226)
NCT ID: NCT02163226
Last Updated: 2021-11-08
Results Overview
Evaluate single fraction stereotactic regimen for pain response in terms of time to failure. Pain response was defined by international consensus criteria as a combination of pain score and analgesic use (daily morphine-equivalent dose). Pain failure (ie, lack of response) was defined as worsening pain score (2 points on a 0-to-10 scale), an increase in morphine-equivalent opioid dose of 50% or more, reirradiation, or pathologic fracture. Time to failure was defined as the first occurrence of any of the following events: worsening in pain score by at least 2 categories by MDASI survey. Statistical tests in treatment group were based on the Wilcoxon rank sum test to compare changes in pain scores and analgesic use at each assessment point relative to baseline. Increases or decreases of 2 or more points on a scale of 0 to 10 indicated improving or worsening pain. Fisher exact tests were used to compare the distribution of pain responders (CR + PR) and nonresponders (PP + IR).
COMPLETED
PHASE2/PHASE3
167 participants
From date of registration until the date of first documented Pain failure or death from any cause, or lost to follow up, whichever came first, assessed up to 9 months
2021-11-08
Participant Flow
There was total 167 patients enrolled in this phase II 2013-0640 palliation of symptoms study. Eligible criteria: pathologic diagnosis of malignancy; any radiographic evidence of bone metastases; with pain or dysathesia; life expectancy of more than 3 months; should not treat more than 3 separate radiation treatment fields concurrently.
A total of 167 patients were consented to this study, but 1 patient withdrew consent prior to protocol treatment, 3 patients insurance denied, 2 Patient condition deteriorated, 1 Pathologic fracture on reevaluation, only 160 patients was randomized and treated under this protocol.
Participant milestones
| Measure |
Arm 1: the Standard Hypofractionated Regimen (MFRT Group)
3 Gy x 10 fractions; Patients can be treated with 2-D, 3-D, or intensity modulated radiation therapy (IMRT)
|
Arm 2: Single-fraction Stereotactic Radiation (SBRT Group)
12 Gy x 1 fraction or 16 Gy x 1 fractions, depending on the size of the metastases or gross tumor volume (GTV), treated with 2-D, 3-D, or IMRT
|
|---|---|---|
|
Overall Study
STARTED
|
79
|
81
|
|
Overall Study
COMPLETED
|
63
|
70
|
|
Overall Study
NOT COMPLETED
|
16
|
11
|
Reasons for withdrawal
| Measure |
Arm 1: the Standard Hypofractionated Regimen (MFRT Group)
3 Gy x 10 fractions; Patients can be treated with 2-D, 3-D, or intensity modulated radiation therapy (IMRT)
|
Arm 2: Single-fraction Stereotactic Radiation (SBRT Group)
12 Gy x 1 fraction or 16 Gy x 1 fractions, depending on the size of the metastases or gross tumor volume (GTV), treated with 2-D, 3-D, or IMRT
|
|---|---|---|
|
Overall Study
Death
|
2
|
1
|
|
Overall Study
Withdrawal by Subject
|
5
|
2
|
|
Overall Study
Returned home, local radiotherapy
|
3
|
0
|
|
Overall Study
Repeat imaging showed no disease
|
2
|
0
|
|
Overall Study
Incomplete radiotherapy
|
3
|
0
|
|
Overall Study
Treatment was to >3 radiotherapy fields
|
1
|
0
|
|
Overall Study
"Insurance denied for single-fraction treatment"
|
0
|
5
|
|
Overall Study
ineligible
|
0
|
3
|
Baseline Characteristics
A Randomized Trial Evaluating Rapid Delivery of Dose Escalated Hypofractionated Radiotherapy for Patients Diagnosed With Bone Metastases for Effective Palliation of Symptoms
Baseline characteristics by cohort
| Measure |
Arm 1: the Standard Hypofractionated Regimen (MFRT Group)
n=79 Participants
3 Gy x 10 fractions; Patients can be treated with 2-D, 3-D, or intensity modulated radiation therapy (IMRT)
|
Arm 2: Single-fraction Stereotactic Radiation (SBRT Group)
n=81 Participants
12 Gy x 1 fraction or 16 Gy x 1 fractions, depending on the size of the metastases or gross tumor volume (GTV), treated with 2-D, 3-D, or IMRT
|
Total
n=160 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
40 Participants
n=5 Participants
|
36 Participants
n=7 Participants
|
76 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
39 Participants
n=5 Participants
|
45 Participants
n=7 Participants
|
84 Participants
n=5 Participants
|
|
Age, Continuous
|
63 years
n=5 Participants
|
63 years
n=7 Participants
|
63 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
32 Participants
n=5 Participants
|
32 Participants
n=7 Participants
|
64 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
47 Participants
n=5 Participants
|
49 Participants
n=7 Participants
|
96 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
4 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
69 Participants
n=5 Participants
|
73 Participants
n=7 Participants
|
142 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
6 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
5 Participants
n=5 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
|
|
Race (NIH/OMB)
Black or African American
|
8 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
59 Participants
n=5 Participants
|
68 Participants
n=7 Participants
|
127 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
10 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
79 participants
n=5 Participants
|
81 participants
n=7 Participants
|
160 participants
n=5 Participants
|
|
Number of Lesions
≤4
|
41 Participants
n=5 Participants
|
42 Participants
n=7 Participants
|
83 Participants
n=5 Participants
|
|
Number of Lesions
>4
|
38 Participants
n=5 Participants
|
39 Participants
n=7 Participants
|
77 Participants
n=5 Participants
|
|
Site of Bony Mets
Abdomen
|
4 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Site of Bony Mets
Thorax
|
9 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
19 Participants
n=5 Participants
|
|
Site of Bony Mets
Extremities
|
13 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
28 Participants
n=5 Participants
|
|
Site of Bony Mets
Head/Neck
|
2 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Site of Bony Mets
Pelvis
|
48 Participants
n=5 Participants
|
46 Participants
n=7 Participants
|
94 Participants
n=5 Participants
|
|
Site of Bony Mets
Spine
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Numbers of Sites Irradiated
1
|
64 Participants
n=5 Participants
|
61 Participants
n=7 Participants
|
125 Participants
n=5 Participants
|
|
Numbers of Sites Irradiated
>1
|
15 Participants
n=5 Participants
|
20 Participants
n=7 Participants
|
35 Participants
n=5 Participants
|
|
Karnofsky performance score (KPS)
KPS 50-60
|
10 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
19 Participants
n=5 Participants
|
|
Karnofsky performance score (KPS)
KPS 70-80
|
58 Participants
n=5 Participants
|
57 Participants
n=7 Participants
|
115 Participants
n=5 Participants
|
|
Karnofsky performance score (KPS)
KPS 90-100
|
11 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
26 Participants
n=5 Participants
|
|
Primary Cancer Site
Adrenal-cortical
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Primary Cancer Site
Bladder
|
4 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Primary Cancer Site
Breast
|
3 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
|
Primary Cancer Site
Esophagus
|
4 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Primary Cancer Site
Head and Neck
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Primary Cancer Site
Liver
|
0 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Primary Cancer Site
Lung
|
47 Participants
n=5 Participants
|
32 Participants
n=7 Participants
|
79 Participants
n=5 Participants
|
|
Primary Cancer Site
Pancreas
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Primary Cancer Site
Prostate
|
9 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
23 Participants
n=5 Participants
|
|
Primary Cancer Site
Renal Cell
|
5 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
|
Primary Cancer Site
Thymoma
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Primary Cancer Site
Thyroid
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Primary Cancer Site
Unknown/Lung
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Primary Cancer Site
Uveal Melanoma
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Primary Cancer Site
Multiple Myeloma
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Primary Tumor Histology
Adenocarcinoma
|
50 Participants
n=5 Participants
|
51 Participants
n=7 Participants
|
101 Participants
n=5 Participants
|
|
Primary Tumor Histology
Adenoid Cystic
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Primary Tumor Histology
Adrenal Cortical Carcinoma
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Primary Tumor Histology
Atypical Carcinoid
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Primary Tumor Histology
Carcinoma
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Primary Tumor Histology
Clear Cell
|
5 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
|
Primary Tumor Histology
Ductal Carcinoma
|
0 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Primary Tumor Histology
Lobular Carcinoma
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Primary Tumor Histology
Melanoma
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Primary Tumor Histology
Neuroendocrine
|
1 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Primary Tumor Histology
Papillary
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Primary Tumor Histology
Pleiomorphic Carcinoma
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Primary Tumor Histology
Poorly Diff Carcinoma
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Primary Tumor Histology
Sarcomatoid
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Primary Tumor Histology
Small Cell
|
1 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Primary Tumor Histology
Squamous
|
6 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Primary Tumor Histology
Urothelial Carcinoma
|
4 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Primary Tumor Histology
Other
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: From date of registration until the date of first documented Pain failure or death from any cause, or lost to follow up, whichever came first, assessed up to 9 monthsEvaluate single fraction stereotactic regimen for pain response in terms of time to failure. Pain response was defined by international consensus criteria as a combination of pain score and analgesic use (daily morphine-equivalent dose). Pain failure (ie, lack of response) was defined as worsening pain score (2 points on a 0-to-10 scale), an increase in morphine-equivalent opioid dose of 50% or more, reirradiation, or pathologic fracture. Time to failure was defined as the first occurrence of any of the following events: worsening in pain score by at least 2 categories by MDASI survey. Statistical tests in treatment group were based on the Wilcoxon rank sum test to compare changes in pain scores and analgesic use at each assessment point relative to baseline. Increases or decreases of 2 or more points on a scale of 0 to 10 indicated improving or worsening pain. Fisher exact tests were used to compare the distribution of pain responders (CR + PR) and nonresponders (PP + IR).
Outcome measures
| Measure |
Arm 1: the Standard Hypofractionated Regimen (MFRT Group)
n=79 Participants
3 Gy x 10 fractions; Patients can be treated with 2-D, 3-D, or intensity modulated radiation therapy (IMRT)
|
Arm 2: Single-fraction Stereotactic Radiation (SBRT Group)
n=81 Participants
12 Gy x 1 fraction or 16 Gy x 1 fractions, depending on the size of the metastases or gross tumor volume (GTV), treated with 2-D, 3-D, or IMRT
|
|---|---|---|
|
Number of Intent- to- Treat Patients With Pain Response by Treatment
Pain Response (CR+PR) at 2 weeks
|
19 Participants
|
34 Participants
|
|
Number of Intent- to- Treat Patients With Pain Response by Treatment
Pain Response (CR+PR) at 1 month
|
24 Participants
|
36 Participants
|
|
Number of Intent- to- Treat Patients With Pain Response by Treatment
Pain Response (CR+PR) at 3 months
|
17 Participants
|
31 Participants
|
|
Number of Intent- to- Treat Patients With Pain Response by Treatment
Pain Response (CR+PR) at 6 months
|
17 Participants
|
19 Participants
|
|
Number of Intent- to- Treat Patients With Pain Response by Treatment
Pain Response (CR+PR) at 9 months
|
12 Participants
|
17 Participants
|
PRIMARY outcome
Timeframe: From date of registration until the date of first documented Pain failure or death from any cause, or lost to follow up, whichever came first, assessed up to 9 monthsEvaluate single fraction stereotactic regimen for pain response in terms of time to failure. Pain response was defined by international consensus criteria as a combination of pain score and analgesic use (daily morphine-equivalent dose). Pain failure (ie, lack of response) was defined as worsening pain score (2 points on a 0-to-10 scale), an increase in morphine-equivalent opioid dose of 50% or more, reirradiation, or pathologic fracture. Time to failure was defined as the first occurrence of any of the following events: worsening in pain score by at least 2 categories by MDASI survey. Complete response (CR) is a pain score of 0 at the treated site and no increase in analgesic. Partial response (PR): reduction in pain score of 2 or more points above baseline with no increase in analgesic. Pain progression (PP): Increases of 2 or more points on a scale of 0 to 10 or worsening pain. indeterminate response (IR): were all other responses.
Outcome measures
| Measure |
Arm 1: the Standard Hypofractionated Regimen (MFRT Group)
n=52 Participants
3 Gy x 10 fractions; Patients can be treated with 2-D, 3-D, or intensity modulated radiation therapy (IMRT)
|
Arm 2: Single-fraction Stereotactic Radiation (SBRT Group)
n=55 Participants
12 Gy x 1 fraction or 16 Gy x 1 fractions, depending on the size of the metastases or gross tumor volume (GTV), treated with 2-D, 3-D, or IMRT
|
|---|---|---|
|
Number of Evaluable Participants With Pain Response by Treatment
Pain Response (CR+PR) at 2 weeks
|
19 Participants
|
34 Participants
|
|
Number of Evaluable Participants With Pain Response by Treatment
Pain Response (CR+PR) at 1 month
|
24 Participants
|
36 Participants
|
|
Number of Evaluable Participants With Pain Response by Treatment
Pain Response (CR+PR) at 3 months
|
17 Participants
|
32 Participants
|
|
Number of Evaluable Participants With Pain Response by Treatment
Pain Response (CR+PR) at 6 months
|
17 Participants
|
19 Participants
|
|
Number of Evaluable Participants With Pain Response by Treatment
Pain Response (CR+PR) at 9 months
|
12 Participants
|
17 Participants
|
SECONDARY outcome
Timeframe: From date of registration until the date of documented death from any cause, or lost to follow up, whichever came first, assessed up to 2 years.Report grade 3 acute (skin, fatigue, flare reaction) and long term (sclerosis, bone ossification, bone fracture rate) toxicity associated with treatment. During radiotherapy, the patient will be examined weekly and acute reactions recorded and toxicity occurring after 3 months of radiation therapy.
Outcome measures
| Measure |
Arm 1: the Standard Hypofractionated Regimen (MFRT Group)
n=79 Participants
3 Gy x 10 fractions; Patients can be treated with 2-D, 3-D, or intensity modulated radiation therapy (IMRT)
|
Arm 2: Single-fraction Stereotactic Radiation (SBRT Group)
n=81 Participants
12 Gy x 1 fraction or 16 Gy x 1 fractions, depending on the size of the metastases or gross tumor volume (GTV), treated with 2-D, 3-D, or IMRT
|
|---|---|---|
|
Number of Participants With Toxicity Associated With Treatment
Nausea
|
4 Participants
|
1 Participants
|
|
Number of Participants With Toxicity Associated With Treatment
Vomiting
|
2 Participants
|
0 Participants
|
|
Number of Participants With Toxicity Associated With Treatment
Fatigue
|
4 Participants
|
9 Participants
|
|
Number of Participants With Toxicity Associated With Treatment
Radiation Dermatitis
|
2 Participants
|
1 Participants
|
|
Number of Participants With Toxicity Associated With Treatment
Fracture
|
0 Participants
|
1 Participants
|
Adverse Events
Arm 1: the Standard Hypofractionated Regimen (MFRT Group)
Arm 2: Single-fraction Stereotactic Radiation (SBRT Group)
Serious adverse events
| Measure |
Arm 1: the Standard Hypofractionated Regimen (MFRT Group)
n=79 participants at risk
3 Gy x 10 fractions; Patients can be treated with 2-D, 3-D, or intensity modulated radiation therapy (IMRT)
|
Arm 2: Single-fraction Stereotactic Radiation (SBRT Group)
n=81 participants at risk
12 Gy x 1 fraction or 16 Gy x 1 fractions, depending on the size of the metastases or gross tumor volume (GTV), treated with 2-D, 3-D, or IMRT
|
|---|---|---|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
19.0%
15/79 • Number of events 18 • From the time of registration to the time of the adverse events (AEs) start date, assessed up to 2 years
|
6.2%
5/81 • Number of events 6 • From the time of registration to the time of the adverse events (AEs) start date, assessed up to 2 years
|
|
General disorders
Fatigue
|
5.1%
4/79 • Number of events 4 • From the time of registration to the time of the adverse events (AEs) start date, assessed up to 2 years
|
11.1%
9/81 • Number of events 9 • From the time of registration to the time of the adverse events (AEs) start date, assessed up to 2 years
|
|
Gastrointestinal disorders
Nausea
|
5.1%
4/79 • Number of events 4 • From the time of registration to the time of the adverse events (AEs) start date, assessed up to 2 years
|
1.2%
1/81 • Number of events 1 • From the time of registration to the time of the adverse events (AEs) start date, assessed up to 2 years
|
|
Gastrointestinal disorders
Vomiting
|
2.5%
2/79 • Number of events 2 • From the time of registration to the time of the adverse events (AEs) start date, assessed up to 2 years
|
0.00%
0/81 • From the time of registration to the time of the adverse events (AEs) start date, assessed up to 2 years
|
Other adverse events
Adverse event data not reported
Additional Information
Dr. Quynh-Nhu Nguyen, MD,Associate Professor, Radiation Oncology Department
UT MD Anderson Cancer Center
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place