Melanoma, Metastatic Malignant Neoplasm in the Spine, Renal Cell Carcinoma, Soft Tissue Sarcoma, Spinal Cord Compression
Conditions
Brief summary
This pilot clinical trial studies adaptive staged stereotactic body radiation therapy (SBRT) in treating patients with spinal metastases that cannot be removed by surgery. SBRT is a specialized radiation therapy that delivers a single, high dose of radiation directly to the tumor and may kill more tumor cells and cause less damage to normal tissue. Adaptive SBRT uses information gathered during treatment to inform, guide, and alter future radiation treatments. Staged SBRT uses multiple treatments separated by 2-3 weeks. Giving adaptive staged SBRT may work better in treating spinal metastases that cannot be removed by surgery.
Detailed description
PRIMARY OBJECTIVES: I. To assess the feasibility of single-fraction radiotherapy to provide a short-interval treatment response in patients with metastatic epidural spinal cord compression (MESCC), such that additional stereotactic radiotherapy to full therapeutic doses can be delivered while respecting spinal cord constraints, based on the following metrics: shortest distance between gross disease and the spinal cord before and after treatment; epidural tumor volume before and after treatment; and extent of epidural compression before and after treatment. SECONDARY OBJECTIVES: I. To evaluate pain control using the Numerical Rating Pain Scale (NRPS) before and after treatment. II. To evaluate patient quality of life using the Functional Assessment of Cancer Therapy-General (FACT-G) before and after treatment. III. To evaluate functional outcomes using ambulation score and standardized neurologic exams before and after treatment. OUTLINE: Patients undergo adaptive staged SBRT. Within 14-21 days, patients may undergo a second treatment of adaptive staged SBRT at the discretion of the treating physician based on clinical parameters, diagnostic interval imaging, and achievement of spinal cord dose constraints. After completion of study treatment, patients are followed up periodically.
Interventions
Undergo adaptive staged SBRT
OTHERQuality-of-Life Assessment
Ancillary studies
OTHERQuestionnaire Administration
Ancillary studies
RADIATIONStereotactic Body Radiation Therapy
Undergo adaptive staged SBRT
Sponsors
National Cancer Institute (NCI)
Albert Einstein College of Medicine
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Localized spine metastasis from the cervical (C)1 to lumbar (L)5 levels with documented epidural cord compression by a screening imaging study (magnetic resonance imaging \[MRI\] or computed tomography \[CT\] myelogram); site may have a maximal involvement of 2 contiguous vertebral bodies; patients with other visceral metastasis, and radioresistant tumors (including soft tissue sarcomas, melanomas, and renal cell carcinomas) are eligible * History/physical examination by the treating physician within 24 hours prior to registration * Neurological and functional examination within 24 hours prior to registration by the treating physician * Negative serum pregnancy test * MRI (contrast is not required but strongly recommended) or CT myelogram of the involved spine within 1 week prior to registration to determine the extent of the spine involvement * Numerical rating pain scale within 1 week prior to registration; documentation of the patient's initial pain score is required; patients taking medication for pain at the time of registration are eligible * Women of childbearing potential must: * Have a negative serum or urine pregnancy test within 72 hours prior to the start of study therapy * Agree to utilize an adequate method of contraception throughout treatment and for at least 4 weeks after study therapy is completed * Be advised of the importance of avoiding pregnancy during trial participation and the potential risks of an unintentional pregnancy * All patients must sign study specific informed consent prior to study entry or within 1 week of first treatment, provided other criteria were met * Patients considered for enrollment are strongly recommended to have been discussed at multidisciplinary tumor board with input from surgery, medical oncology and radiation oncology prior to enrollment
Exclusion criteria
* Histologies of myeloma or lymphoma * Cord compression at 2 non-contiguous sites in the spine * Favorable candidates for surgical decompression by prior documented criteria * Spine instability as determined by Spinal Instability Neoplastic Score (SINS) score \> 12 * \> 50% loss of vertebral body height * Bony retropulsion causing neurologic abnormality * Prior radiation to the index spine * Patients who cannot obtain a contrast-enhanced MRI or CT myelogram due to allergy, renal failure or other medical contraindication
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Distance Between the Gross Disease and Spinal Cord (Cord-disease Distance, CDD) of at Least 3mm After Treatment. | Up to 10 weeks after first treatment | Cord-disease distance of at least 3mm in shortest axial distance after treatment. Data was summarized using standard descriptive statistics; formal hypothesis testing was not performed. Confidence intervals for the true proportion were computed using Clopper-Pearson exact confidence interval were not conducted. Since this was a feasibility, study no power calculation was done. |
| Number of Participants Demonstrating Successful Radiographic Response of the Spinal Tumor | Up to 10 weeks after first treatment | Successful radiographic response of the spinal tumor was determined by achieving of a 10% reduction in epidural volume or thecal sac compression (i.e., \ 10% absolute increase in thecal sac patency (TSP)) following treatment, on either of their MRI imaging or CT myelogram scans. Data was summarized using standard descriptive statistics; formal hypothesis testing was not performed. Confidence intervals for the true proportion using Clopper-Pearson exact confidence interval were not conducted. Since this is a feasibility study no power calculation was done. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Health Related Quality of Life Scores (FACT-G) | Up to 3 months following first treatment | Health-related Quality of Life was measured using Functional Assessment of Cancer Therapy - General (FACT-G) a 27-item questionnaire designed to measure four domains of Quality of Life in cancer patients assessed over the previous 7-day period: physical well-being (7 questions), social/family well-being (7 questions), emotional being (6 questions), and functional well-being (7 questions). Participant responses are assessed using a 5 point Likert-type scale ranging from 0 (Not at all) to 4 (Very much). A FACT-G total score is computed as the sum of the four subscale scores, provided the overall item response is at least 80% (i.e. at least 22 of the 27 items answered) and has a possible range of 0-108 points. Negatively worded items are reverse scored prior to summing so that higher subscale and total scores indicate a better overall health state corresponding Quality of Life. |
| Incidence of Any Grade Greater Than or Equal to 3 Treatment-related Toxicity, Scored Using CTCAE, v. 4 | Up to 2 years | Data will be reported in a descriptive manner to describe any incidence of greater than or equal to 3 treatment related toxicity |
| Change in Ambulation (Mobility) | 10 weeks after first treatment | Ambulation was assessed as a functional outcome by the treating physician. Scoring was adapted from the ICORG Phase III trial, ASTRO 2014. Mobility scores were assigned as follows: 1 = ambulatory without aid; 2 = ambulatory with aid; 3 = not ambulatory; and 4 = paraplegia. Basic descriptive statistics were used to assess changes in ambulation from baseline. |
| Overall Survival | From study registration to death, censored at the date of data collection, assessed up to 2 years | Data will be reported in a descriptive manner. |
| Progression-free Survival | From study registration to date of disease progression or death, censored at the date of data collection, assessed up to 2 years | Data will be reported in a descriptive manner. |
| Incidence of Grade Greater Than or Equal to 2 Radiation-induced Lung Toxicity (CTCAE), Version (v.) 4 | Up to 2 years | Data will be reported in a descriptive manner to describe any incidence of grade 2 or greater related radiation induced lung toxicity |
| Change in Pain Control in Terms of Pain Scores as Measured by the Numeric Pain Rating Scale (NPRS) Estimation | Up to 10 weeks after first treatment | Participants were asked to provide a numeric value using the NPRS to describe their pain intensity. The NPRS is a unidimensional assessment tool which measures pain on an 11-point (0-10) numeric scale where 0 represents no pain and 10 represents extreme pain. Higher scores are indicative of worsening pain intensity. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Adaptive Staged SBRT) Patients undergo adaptive staged SBRT. Within 14-21 days, patients may undergo a second treatment of adaptive staged SBRT at the discretion of the treating physician based on clinical parameters, diagnostic interval imaging, and achievement of spinal cord dose constraints.
Image-Guided Adaptive Radiation Therapy: Undergo adaptive staged SBRT
Quality-of-Life Assessment: Ancillary studies
Questionnaire Administration: Ancillary studies
Stereotactic Body Radiation Therapy: Undergo adaptive staged SBRT | 24 |
| Total | 24 |
Baseline characteristics
| Characteristic | Treatment (Adaptive Staged SBRT) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 14 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants |
| Age, Continuous | 66.5 years |
| Numeric Pain Rating Scale | 4.31 units on a scale STANDARD_DEVIATION 3 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 12 Participants |
| Race (NIH/OMB) More than one race | 5 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) White | 4 Participants |
| Region of Enrollment United States | 24 Participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 24 |
| other Total, other adverse events | 5 / 24 |
| serious Total, serious adverse events | 0 / 24 |
Outcome results
Primary
Distance Between the Gross Disease and Spinal Cord (Cord-disease Distance, CDD) of at Least 3mm After Treatment.
Cord-disease distance of at least 3mm in shortest axial distance after treatment. Data was summarized using standard descriptive statistics; formal hypothesis testing was not performed. Confidence intervals for the true proportion were computed using Clopper-Pearson exact confidence interval were not conducted. Since this was a feasibility, study no power calculation was done.
Time frame: Up to 10 weeks after first treatment
Population: Data was not collected and analyzed for 9 participants due to no post-treatment imaging being obtained. Imaging was unable to be conducted for these participants due to either a decline in subjects' clinical status or death. Confidence intervals were not determined given data limitations and had no impact due to feasibility design of study.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment (Adaptive Staged SBRT) | Distance Between the Gross Disease and Spinal Cord (Cord-disease Distance, CDD) of at Least 3mm After Treatment. | met primary endpoint of CDD >3 mm | 1 Participants |
| Treatment (Adaptive Staged SBRT) | Distance Between the Gross Disease and Spinal Cord (Cord-disease Distance, CDD) of at Least 3mm After Treatment. | did not meet primary endpoint of CDD >3 mm | 14 Participants |
Primary
Number of Participants Demonstrating Successful Radiographic Response of the Spinal Tumor
Successful radiographic response of the spinal tumor was determined by achieving of a 10% reduction in epidural volume or thecal sac compression (i.e., \ 10% absolute increase in thecal sac patency (TSP)) following treatment, on either of their MRI imaging or CT myelogram scans. Data was summarized using standard descriptive statistics; formal hypothesis testing was not performed. Confidence intervals for the true proportion using Clopper-Pearson exact confidence interval were not conducted. Since this is a feasibility study no power calculation was done.
Time frame: Up to 10 weeks after first treatment
Population: Data was not collected and analyzed for 10 participants due to no post-treatment MRI or CT myelograms being obtained. Imaging was unable to be conducted for these 10 participants due to either a decline in subjects' clinical status or death. Confidence intervals were not determined given data limitations and had no impact due to feasibility design of study.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment (Adaptive Staged SBRT) | Number of Participants Demonstrating Successful Radiographic Response of the Spinal Tumor | Participants with significant TSP difference | 8 Participants |
| Treatment (Adaptive Staged SBRT) | Number of Participants Demonstrating Successful Radiographic Response of the Spinal Tumor | Participants without significant TSP difference | 6 Participants |
Secondary
Change in Ambulation (Mobility)
Ambulation was assessed as a functional outcome by the treating physician. Scoring was adapted from the ICORG Phase III trial, ASTRO 2014. Mobility scores were assigned as follows: 1 = ambulatory without aid; 2 = ambulatory with aid; 3 = not ambulatory; and 4 = paraplegia. Basic descriptive statistics were used to assess changes in ambulation from baseline.
Time frame: 10 weeks after first treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment (Adaptive Staged SBRT) | Change in Ambulation (Mobility) | .3 Change in ambulation measure score | Standard Deviation 3 |
Secondary
Change in Pain Control in Terms of Pain Scores as Measured by the Numeric Pain Rating Scale (NPRS) Estimation
Participants were asked to provide a numeric value using the NPRS to describe their pain intensity. The NPRS is a unidimensional assessment tool which measures pain on an 11-point (0-10) numeric scale where 0 represents no pain and 10 represents extreme pain. Higher scores are indicative of worsening pain intensity.
Time frame: Up to 10 weeks after first treatment
Population: Data was not collected and analyzed for all patient due to diminishing clinical status or death.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment (Adaptive Staged SBRT) | Change in Pain Control in Terms of Pain Scores as Measured by the Numeric Pain Rating Scale (NPRS) Estimation | pretreatment best | 4.3 score on a scale | Standard Deviation 3 |
| Treatment (Adaptive Staged SBRT) | Change in Pain Control in Terms of Pain Scores as Measured by the Numeric Pain Rating Scale (NPRS) Estimation | pretreatment worst | 7.18 score on a scale | Standard Deviation 2.8 |
| Treatment (Adaptive Staged SBRT) | Change in Pain Control in Terms of Pain Scores as Measured by the Numeric Pain Rating Scale (NPRS) Estimation | weeks 2-4 best | 3.46 score on a scale | Standard Deviation 2.6 |
| Treatment (Adaptive Staged SBRT) | Change in Pain Control in Terms of Pain Scores as Measured by the Numeric Pain Rating Scale (NPRS) Estimation | weeks 2-4 worst | 5.85 score on a scale | Standard Deviation 3.7 |
| Treatment (Adaptive Staged SBRT) | Change in Pain Control in Terms of Pain Scores as Measured by the Numeric Pain Rating Scale (NPRS) Estimation | weeks 8-10 best | 2.85 score on a scale | Standard Deviation 3.6 |
| Treatment (Adaptive Staged SBRT) | Change in Pain Control in Terms of Pain Scores as Measured by the Numeric Pain Rating Scale (NPRS) Estimation | weeks 8-10 worst | 6 score on a scale | Standard Deviation 3.5 |
Secondary
Health Related Quality of Life Scores (FACT-G)
Health-related Quality of Life was measured using Functional Assessment of Cancer Therapy - General (FACT-G) a 27-item questionnaire designed to measure four domains of Quality of Life in cancer patients assessed over the previous 7-day period: physical well-being (7 questions), social/family well-being (7 questions), emotional being (6 questions), and functional well-being (7 questions). Participant responses are assessed using a 5 point Likert-type scale ranging from 0 (Not at all) to 4 (Very much). A FACT-G total score is computed as the sum of the four subscale scores, provided the overall item response is at least 80% (i.e. at least 22 of the 27 items answered) and has a possible range of 0-108 points. Negatively worded items are reverse scored prior to summing so that higher subscale and total scores indicate a better overall health state corresponding Quality of Life.
Time frame: Up to 3 months following first treatment
Population: Data was not collected and analyzed for 15 participants due to either a decline in subjects' clinical status or death.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment (Adaptive Staged SBRT) | Health Related Quality of Life Scores (FACT-G) | 5 score on a scale | Standard Deviation 3 |
Secondary
Incidence of Any Grade Greater Than or Equal to 3 Treatment-related Toxicity, Scored Using CTCAE, v. 4
Data will be reported in a descriptive manner to describe any incidence of greater than or equal to 3 treatment related toxicity
Time frame: Up to 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (Adaptive Staged SBRT) | Incidence of Any Grade Greater Than or Equal to 3 Treatment-related Toxicity, Scored Using CTCAE, v. 4 | 0 Participants |
Secondary
Incidence of Grade Greater Than or Equal to 2 Radiation-induced Lung Toxicity (CTCAE), Version (v.) 4
Data will be reported in a descriptive manner to describe any incidence of grade 2 or greater related radiation induced lung toxicity
Time frame: Up to 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (Adaptive Staged SBRT) | Incidence of Grade Greater Than or Equal to 2 Radiation-induced Lung Toxicity (CTCAE), Version (v.) 4 | 0 Participants |
Secondary
Overall Survival
Data will be reported in a descriptive manner.
Time frame: From study registration to death, censored at the date of data collection, assessed up to 2 years
Population: patients
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (Adaptive Staged SBRT) | Overall Survival | 13 Participants |
Secondary
Progression-free Survival
Data will be reported in a descriptive manner.
Time frame: From study registration to date of disease progression or death, censored at the date of data collection, assessed up to 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (Adaptive Staged SBRT) | Progression-free Survival | 12 Participants |