Metastatic Carcinoma
Conditions
Brief summary
This is a multi-site single arm feasibility study of single-fraction Stereotactic MRI-guided Adaptive Radiation Therapy (SMART) for primary or metastatic carcinoma involving the lung, liver, adrenal gland, abdominal/pelvic lymph node, pancreas, and/or kidney. Stereotactic ablative body radiation therapy (SABR) is a highly-focused radiation treatment that gives an intense dose of radiation concentrated on a tumor, while limiting the dose to the surrounding organs.
Interventions
Single-fraction of stereotactic ablative body radiation (SABR) therapy will be delivered with an integrated magnetic resonance imaging (MRI)-guided radiotherapy delivery system (ViewRay MRIdian Linac). The prescription dose is dependent on the anatomic location of the lesion and based on previously published safety data.
Sponsors
Viewray Inc.
Baptist Health South Florida
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
1. Subject must be ≥18 years of age at the time of study enrollment 2. Subject must have Biopsy-confirmed primary or metastatic carcinoma with involvement of the lung, liver, adrenal gland, pancreas, kidney, and/or abdominal/pelvic lymph node that would receive SABR 3. Any lesion that would receive SABR under this study protocol is no larger than 5 cm in greatest dimension 4. 1-10 total lesions that would receive SABR 5. If multiple lesions are treated, they must be at least 3 cm apart 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 7. Life expectancy at least 6 months 8. Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation. Abstinence is acceptable if it's the patient preferred method. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately. 9. Patients receiving hormonal therapy or immunotherapy such as immune checkpoint inhibitor that had begun at least 4 weeks prior to SABR will be allowed.
Exclusion criteria
1. Subject has contraindication to having an MRI scan 2. Subject has central or ultra-central lung tumor that would receive SABR on this study, defined as a lesion located within 2 cm of the trachea and proximal bronchial tree 3. Subject has received cytotoxic chemotherapy or investigational agent within 2 weeks of SBRT 4. Subject has uncontrolled brain metastases, spinal cord compression, or leptomeningeal carcinomatosis 5. Subject has any unresolved toxicity (Common Terminology Criteria for Adverse Events version 5.0 \> grade 2) from previous anti-cancer therapy 6. Subject has any condition in the opinion of the investigator that would interfere with evaluation of study treatment or interpretation of patient safety or study results 7. Subject has received prior radiation therapy that directly overlaps any radiation therapy given in this study 8. Subject has received radiation therapy that could lead to an unacceptably high risk of clinically significant normal tissue injury due to high cumulative normal tissue dose as determined by the investigator 9. Female subject who are pregnant or breastfeeding 10. Subject who has received vascular endothelial growth factor (VEGF) inhibitor such as bevacizumab within 4 weeks prior to study therapy or planned to receive it within 4 weeks after study therapy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With SABR Successfully Delivered in One Fraction | through study completion, an average of 1 year | To be considered successful, SABR treatment must meet the following criteria: 1. Successful completion of treatment to each lesion within 3 days of intended treatment date 2. Successful completion of treatment to each lesion within 90 minutes from the patient entering the treatment room until treatment completion for at least 80% of treated lesions 3. Image guidance verification of treatment delivery within 5 mm of the planned delivery |
| Number of Patients Demonstrating Tolerability | through study completion, an average of 1 year | Number of patients that meet the following criteria: 1. No greater than 4 of 30 patients experience grade 3 or higher acute toxicity is attributable to SABR within 90 days of completing SABR 2. No grade 5 toxicity is attributed to SABR |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| One-year Local Control | 12 months | Assessed using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and estimated with Kaplan-Meier and corresponding 95% confidence interval from the time of study treatment. Target lesion: * Complete response (CR): Disappearance of all target lesions * Partial response (PR): \>30% decrease in the sum of the diameters of target lesions * Stable disease (SD): Target lesion has neither sufficient decrease to qualify as a PR or sufficient increase to qualify as progressive disease (PD) * PD: At least a 20% increase in the sum of the diameters of target lesions an absolute increase of at least 5 mm Non-target lesion: * CR: Disappearance of all non-target lesions * SD: Persistence of ≥1 non-target lesions * PD: Appearance of ≥1 new lesions or unequivocal progression of existing non-target lesions Overall: * CR: Target CR+non-target CR * PR: Target CR/PR+non-target non-PD * SD: Target SD+non-target non-PD * PD: Anything else Local control=CR+PR+SD using overall response. |
| Percent of Participants With One-year Overall Survival | 12 months | Percent of participants with one-year overall survival will be estimated using the Kaplan-Meier method along with the corresponding 95% confidence interval from the time of study treatment. |
| Number of Participants With Acute and Late Toxicity Results | 12 months | Number of participants with acute and late toxicities defined as grade 3 or higher toxicity attributable to SABR will be determined. For patients receiving SABR to multiple lesions, acute toxicity will be determined from the date of the initiation of SABR. |
| Change in Participant Reported Quality of Life Questionnaire | baseline, 3, 6, 9, and 12 months after treatment | Patient-reported quality of life will be determined using the Functional Assessment of Cancer Therapy - General (FACT-G) survey instrument. FACT-G is a 27-item questionnaire that covers four sub-domains: physical (7 items), social (7 items), emotional, (6 items), and functional (7 items) well-being. Each question is scored from a scale from 0 (not at all) to 4 (very much) using a manual scoring template in which some items are reversed. After reversal of specified items, the sub-domain scores are totaled, then multiplied by the number of items in the sub-domain, and then divided by the number of items the participant answered. The scores for each sub-domain are 0 (worst well-being) to 24 (best emotional well-being) or 28 (best physical, social, or functional well-being). The total scores can range from 0 (worst overall well-being) to 108 (best overall well-being). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Single-fraction SABR Patients will receive SABR in a single-fraction regiment treatment with one single dose of radiation therapy per lesion. Patients may be treated for up to a total of ten lesions. Each lesion will be treated in one fraction.
Stereotactic ablative body radiation therapy: Single-fraction of stereotactic ablative body radiation (SABR) therapy will be delivered with an integrated magnetic resonance imaging (MRI)-guided radiotherapy delivery system (ViewRay MRIdian Linac). The prescription dose is dependent on the anatomic location of the lesion and based on previously published safety data. | 30 |
| Single-fraction SABR Patients will receive SABR in a single-fraction regiment treatment with one single dose of radiation therapy per lesion. Patients may be treated for up to a total of ten lesions. Each lesion will be treated in one fraction.
Stereotactic ablative body radiation therapy: Single-fraction of stereotactic ablative body radiation (SABR) therapy will be delivered with an integrated magnetic resonance imaging (MRI)-guided radiotherapy delivery system (ViewRay MRIdian Linac). The prescription dose is dependent on the anatomic location of the lesion and based on previously published safety data. | 32 |
| Total | 62 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| After Treatment | Death | 4 |
| After Treatment | Discharged to hospice | 2 |
| After Treatment | Lost to Follow-up | 1 |
Baseline characteristics
| Characteristic | Single-fraction SABR |
|---|---|
| Age, Continuous | 69 years |
| Anatomic Location Abdominal/pelvic lymph node | 6 lesions |
| Anatomic Location Adrenal gland | 9 lesions |
| Anatomic Location Liver | 5 lesions |
| Anatomic Location Lung | 11 lesions |
| Anatomic Location Pancreas | 1 lesions |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 0 (Fully active, able to carry on all pre-disease performance without restriction) | 12 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 1 (Ambulatory, able to carry out work of a light or sedentary nature) | 18 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 19 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Histology Adenocarcinoma | 17 Participants |
| Histology Non-small cell lung carcinoma | 7 Participants |
| Histology Renal cell carcinoma | 2 Participants |
| Histology Small cell lung carcinoma | 1 Participants |
| Histology Squamous cell carcinoma | 3 Participants |
| Interval from Initial Diagnosis to Enrolment | 20.1 months |
| Maximum Size of Treated Lesions | 1.7 cm |
| Previous Systemic Therapy for Metastatic Disease Chemotherapy and Immunotherapy | 2 participants |
| Previous Systemic Therapy for Metastatic Disease Chemotherapy Only | 10 participants |
| Previous Systemic Therapy for Metastatic Disease Immunotherapy Only | 2 participants |
| Previous Systemic Therapy for Metastatic Disease None | 16 participants |
| Primary or Metastatic Lesions Metastatic | 30 lesions |
| Primary or Metastatic Lesions Primary | 2 lesions |
| Primary Tumor Definitively Managed No | 1 Participants |
| Primary Tumor Definitively Managed Not Applicable | 2 Participants |
| Primary Tumor Definitively Managed Yes | 27 Participants |
| Primary Tumor Location Anal canal | 1 lesions |
| Primary Tumor Location Colon/rectum | 16 lesions |
| Primary Tumor Location Esophagus | 1 lesions |
| Primary Tumor Location Kidney | 2 lesions |
| Primary Tumor Location Lung | 10 lesions |
| Primary Tumor Location Pancreas | 1 lesions |
| Primary Tumor Location Tonsil | 1 lesions |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 29 Participants |
| Region of Enrollment United States | 30 participants |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 16 Participants |
| Total Number of Treated Lesions | 32 lesions |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 4 / 30 |
| other Total, other adverse events | 28 / 30 |
| serious Total, serious adverse events | 3 / 30 |
Outcome results
Primary
Number of Participants With SABR Successfully Delivered in One Fraction
To be considered successful, SABR treatment must meet the following criteria: 1. Successful completion of treatment to each lesion within 3 days of intended treatment date 2. Successful completion of treatment to each lesion within 90 minutes from the patient entering the treatment room until treatment completion for at least 80% of treated lesions 3. Image guidance verification of treatment delivery within 5 mm of the planned delivery
Time frame: through study completion, an average of 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Single-fraction SABR | Number of Participants With SABR Successfully Delivered in One Fraction | 30 Participants |
Primary
Number of Patients Demonstrating Tolerability
Number of patients that meet the following criteria: 1. No greater than 4 of 30 patients experience grade 3 or higher acute toxicity is attributable to SABR within 90 days of completing SABR 2. No grade 5 toxicity is attributed to SABR
Time frame: through study completion, an average of 1 year
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Single-fraction SABR | Number of Patients Demonstrating Tolerability | Did not meet toxicity criteria | 28 Participants |
| Single-fraction SABR | Number of Patients Demonstrating Tolerability | Grade 3 or higher acute toxicity attributable to SABR (excludes Grade 5 toxicities in next category) | 2 Participants |
| Single-fraction SABR | Number of Patients Demonstrating Tolerability | Grade 5 toxicity attributed to SABR | 0 Participants |
Secondary
Change in Participant Reported Quality of Life Questionnaire
Patient-reported quality of life will be determined using the Functional Assessment of Cancer Therapy - General (FACT-G) survey instrument. FACT-G is a 27-item questionnaire that covers four sub-domains: physical (7 items), social (7 items), emotional, (6 items), and functional (7 items) well-being. Each question is scored from a scale from 0 (not at all) to 4 (very much) using a manual scoring template in which some items are reversed. After reversal of specified items, the sub-domain scores are totaled, then multiplied by the number of items in the sub-domain, and then divided by the number of items the participant answered. The scores for each sub-domain are 0 (worst well-being) to 24 (best emotional well-being) or 28 (best physical, social, or functional well-being). The total scores can range from 0 (worst overall well-being) to 108 (best overall well-being).
Time frame: baseline, 3, 6, 9, and 12 months after treatment
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Single-fraction SABR | Change in Participant Reported Quality of Life Questionnaire | Baseline | 84 score on a scale (FACT-G) |
| Single-fraction SABR | Change in Participant Reported Quality of Life Questionnaire | 3 Months | 85 score on a scale (FACT-G) |
| Single-fraction SABR | Change in Participant Reported Quality of Life Questionnaire | 6 Months | 69 score on a scale (FACT-G) |
| Single-fraction SABR | Change in Participant Reported Quality of Life Questionnaire | 9 Months | 91 score on a scale (FACT-G) |
| Single-fraction SABR | Change in Participant Reported Quality of Life Questionnaire | 12 Months | 93 score on a scale (FACT-G) |
Secondary
Number of Participants With Acute and Late Toxicity Results
Number of participants with acute and late toxicities defined as grade 3 or higher toxicity attributable to SABR will be determined. For patients receiving SABR to multiple lesions, acute toxicity will be determined from the date of the initiation of SABR.
Time frame: 12 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Single-fraction SABR | Number of Participants With Acute and Late Toxicity Results | Acute | 2 participants |
| Single-fraction SABR | Number of Participants With Acute and Late Toxicity Results | Late | 0 participants |
Secondary
One-year Local Control
Assessed using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and estimated with Kaplan-Meier and corresponding 95% confidence interval from the time of study treatment. Target lesion: * Complete response (CR): Disappearance of all target lesions * Partial response (PR): \>30% decrease in the sum of the diameters of target lesions * Stable disease (SD): Target lesion has neither sufficient decrease to qualify as a PR or sufficient increase to qualify as progressive disease (PD) * PD: At least a 20% increase in the sum of the diameters of target lesions an absolute increase of at least 5 mm Non-target lesion: * CR: Disappearance of all non-target lesions * SD: Persistence of ≥1 non-target lesions * PD: Appearance of ≥1 new lesions or unequivocal progression of existing non-target lesions Overall: * CR: Target CR+non-target CR * PR: Target CR/PR+non-target non-PD * SD: Target SD+non-target non-PD * PD: Anything else Local control=CR+PR+SD using overall response.
Time frame: 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Single-fraction SABR | One-year Local Control | 96.2 percentage of participants |
Secondary
Percent of Participants With One-year Overall Survival
Percent of participants with one-year overall survival will be estimated using the Kaplan-Meier method along with the corresponding 95% confidence interval from the time of study treatment.
Time frame: 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Single-fraction SABR | Percent of Participants With One-year Overall Survival | 86.3 percentage of participants |