Liver Metastases, Solid Tumor
Conditions
Keywords
proton radiation, stereotactic body radiotherapy, SBRT
Brief summary
Stereotactic body radiation therapy (SBRT) is a technique that is used to deliver radiation, to sites in the body. All participants in this study will be treated with SBRT using proton beam radiation. Proton beam radiation uses tiny particles to deliver radiation to tumors. The purpose of this research study is to determine if SBRT with protons will prevent tumor growth and reduce the treatment side effects for liver metastases.
Detailed description
* Participants receiving SBRT with protons, will receive radiation treatment as an outpatient at the Francis H. Burr Proton Therapy Center at Massachusetts General Hospital. * Not everyone who participates in this study will be receiving the same dose of radiation. The dose received will be determined by the size and location of the tumor(s). * Participants will receive 2-3 SBRT treatments per week for two weeks. * During radiation therapy visits the following tests/procedures will be performed: vital signs, physical examination, routine blood tests, research blood tests, and radiation planning. * Follow-up assessments will be performed once at 9 weeks after study treatment, then at 6 months, 12 months, 18 months and 24 months after treatment.
Interventions
RADIATIONStereotactic body radiotherapy-proton
Dose will be determined by the size and location of the tumor(s); 2-3 treatments per week for two weeks
Sponsors
Dana-Farber Cancer Institute
Brigham and Women's Hospital
National Cancer Institute (NCI)
Massachusetts General Hospital
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
* Biopsy-proven cancer diagnosis of a solid tumor with 1-4 liver metastases. There is no upper size limit. Liver metastases may be diagnosed by imaging alone, no liver biopsy is required. Extrahepatic disease is allowed if it have been stable for 3 months prior to study entry, the dominant disease burden is intrahepatic and the patient is referred for definitive radiation therapy to the disease in the liver * Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension as 10mm or greater with spiral CT scan * Patients may have had prior chemotherapy, targeted biological therapy, surgery, transarterial chemoembolization (TACE), radiofrequency ablation, or cryosurgery for their disease as long as the prior therapy occured greater than 3 weeks elapsed before the first radiation treatment. Patients may not have had prior liver directed radiation, including radioembolization. * 18 years of age or older * Expected survival must be greater than three months * Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 * Patients must have at least 800mL of uninvolved liver * Normal organ and marrow function as outlined in the protocol * If patient has underlying cirrhosis, only Child-Pugh classification Group A patients should be included in this study. Clinical assessment of ascites and encephalopathy is required. Child-Pugh classification must be determined for all study participants at the time of eligibility analysis. * Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation
Exclusion criteria
* Women who are pregnant or lactating * Patients with gross ascites or encephalopathy * Local conditions or systemic illnesses which would reduce the local tolerance to radiation treatment, such as serious local injuries, active collagen vascular disease, etc. * Prior liver directed radiation treatment, including selective internal radiation * No serious medical illness, which may limit survival to less than 3 months * No serious psychiatric illness which would limit compliance with treatment * Participants who have had chemotherapy or radiotherapy within 3 weeks prior to starting study treatment or those who have not recovered from adverse events due to agents administered more than 3 weeks earlier * Participants may not be receiving any other investigational agents, or any other anti-cancer therapy during treatment * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia. * Only solid tumors are permitted. Thus, individuals with a liver mass from a diagnosis of lymphoma or leukemia are excluded
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Local Control Rate | 1 year | The percentage of participants with local control at primary tumor site at one year. Local is evaluated using Response Evaluation Criteria In Solid Tumors (RECIST). Local control is defined as achieving either Complete response (CR), Partial Response (PR), or Stable Disease (SD). * (CR): Disappearance of entire lesion, with no additional evidence of disease. * (PR): At least a 30% decrease in the (sum of) the longest diameter (LD) of the primary lesion, taken as reference the baseline sum LD. * (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median Overall Survival | 2 years | The median overall survival (in months) of participants as measured from the start of treatment. |
| Median Progression Free Survival | 1 years | The median amount of time participants survived without cancer progression following the start of study treatment. Progression was assessed using RECIST v1.0. Progressive Disease (PD) is defined as at least a 20% increase in the Longest Diameter (LD) of the lesion, taken as the reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. |
| Median Follow-up Time | 1 year | The median follow-up time among the 39 participants still alive at the time of analysis, measured from the start of treatment until the time of analysis. |
| 1 Year Local Control Rate Among Participants With Colorectal Cancer | 1 year | The percentage of participants with local control at one year among the participants with colorectal cancer as the primary cancer. |
| Median Survival Among Participants With Colorectal Cancer | 2 years | The median amount of time participants survived from the start of treatment, among the participants with colorectal cancer. |
| 2-year Local Control Rate | 2 years | The percentage of participants with local control 2 years after the start of study treatment. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| SBRT-Proton SBRT by proton radiation
Stereotactic body radiotherapy-proton: Dose will be determined by the size and location of the tumor(s); 2-3 treatments per week for two weeks | 90 |
| Total | 90 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Protocol Violation | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | SBRT-Proton |
|---|---|
| Age, Continuous | 68 years |
| Categorical Tumor size > 10 cm | 7 Participants |
| Categorical Tumor size ≤ 5 cm | 50 Participants |
| Categorical Tumor size > 5 cm | 31 Participants |
| Median Tumor Size | 2.55 Centimeters (cm) |
| Number of Tumors 1 Tumor | 54 Participants |
| Number of Tumors 2 Tumors | 21 Participants |
| Number of Tumors 3 Tumors | 10 Participants |
| Number of Tumors 4 Tumors | 5 Participants |
| Primary Cancer Site Anal | 2 Participants |
| Primary Cancer Site Breast | 3 Participants |
| Primary Cancer Site Colorectal | 35 Participants |
| Primary Cancer Site Esophagogastric | 12 Participants |
| Primary Cancer Site Gallbladder | 3 Participants |
| Primary Cancer Site Head and Neck | 2 Participants |
| Primary Cancer Site Hepatocellular | 8 Participants |
| Primary Cancer Site Lung | 5 Participants |
| Primary Cancer Site Pancreatic | 16 Participants |
| Primary Cancer Site Prostate | 1 Participants |
| Primary Cancer Site Small Bowel or Duodenal | 3 Participants |
| Region of Enrollment United States | 90 Participants |
| Sex: Female, Male Female | 33 Participants |
| Sex: Female, Male Male | 57 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 90 |
| other Total, other adverse events | 86 / 90 |
| serious Total, serious adverse events | 0 / 90 |
Outcome results
Primary
Local Control Rate
The percentage of participants with local control at primary tumor site at one year. Local is evaluated using Response Evaluation Criteria In Solid Tumors (RECIST). Local control is defined as achieving either Complete response (CR), Partial Response (PR), or Stable Disease (SD). * (CR): Disappearance of entire lesion, with no additional evidence of disease. * (PR): At least a 30% decrease in the (sum of) the longest diameter (LD) of the primary lesion, taken as reference the baseline sum LD. * (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.
Time frame: 1 year
Population: The 90 participants that started study treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SBRT-Proton | Local Control Rate | 77 percentage of participants |
Secondary
1 Year Local Control Rate Among Participants With Colorectal Cancer
The percentage of participants with local control at one year among the participants with colorectal cancer as the primary cancer.
Time frame: 1 year
Population: Participants with colorectal cancer
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SBRT-Proton | 1 Year Local Control Rate Among Participants With Colorectal Cancer | 60 percentage of participants |
Secondary
2-year Local Control Rate
The percentage of participants with local control 2 years after the start of study treatment.
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SBRT-Proton | 2-year Local Control Rate | 65.8 percentage of participants |
Secondary
Median Follow-up Time
The median follow-up time among the 39 participants still alive at the time of analysis, measured from the start of treatment until the time of analysis.
Time frame: 1 year
Population: the 39 participants still alive at the time of analysis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SBRT-Proton | Median Follow-up Time | 11 Months |
Secondary
Median Overall Survival
The median overall survival (in months) of participants as measured from the start of treatment.
Time frame: 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SBRT-Proton | Median Overall Survival | 18 Months |
Secondary
Median Progression Free Survival
The median amount of time participants survived without cancer progression following the start of study treatment. Progression was assessed using RECIST v1.0. Progressive Disease (PD) is defined as at least a 20% increase in the Longest Diameter (LD) of the lesion, taken as the reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
Time frame: 1 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SBRT-Proton | Median Progression Free Survival | 4 Months |
Secondary
Median Survival Among Participants With Colorectal Cancer
The median amount of time participants survived from the start of treatment, among the participants with colorectal cancer.
Time frame: 2 years
Population: The 35 participants with colorectal cancer as the primary cancer.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SBRT-Proton | Median Survival Among Participants With Colorectal Cancer | 18 Months |