Adrenal Cancer, Liver Cancer, Non-Small-Cell Lung Carcinoma
Conditions
Keywords
lung cancer, metastatic, SBRT, Stereotactic body radiation therapy, liver, spine, adrenal, bone cancer, Spinal Column
Brief summary
This protocol is a single arm phase II multi-center trial evaluating the efficacy of Stereotactic Body Radiation Therapy (SBRT) in patients with oligometastatic non-small cell lung cancer (NSCLC) with response or stable disease after 4 cycles of first-line chemotherapy. The core hypothesis tested is that SBRT after 4 cycles of first-line chemotherapy is feasible, safe, provides durable local control of treated lesions and improves time to progression compared to historical controls. Patients are eligible for enrollment if they have metastatic NSCLC with ≤5 lesions amenable to SBRT.
Interventions
RADIATIONstereotactic body radiation therapy
For lung, liver, axial skeleton, and adrenal tumors a dose of either 54 Gy in 3 fxs or 5000 cGy in 5 fx using SBRT techniques
Sponsors
Wake Forest University Health Sciences
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
General * Patients with AJCC sixth edition metastatic non-small cell lung carcinoma * Pathologic diagnosis of stage 4 non-small cell lung cancer prior to enrollment. * Patients must have response or stable disease by RECIST criteria after 4 cycles of first-line chemotherapy * Maximum of number of lesions per patient will be 5 total. . * Patients with solitary brain metastases previously treated with surgery or stereotactic radiosurgery (+/- WBRT) and currently controlled at the time of study enrollment are also eligible. Patients with history of brain metastases must have an MRI showing no active brain metastases within 80 days of study enrollment. Patients with a history of brain metastases may have up to 5 extracranial sites of disease except for those with an untreated primary tumor where section 3.1.3.3 will also apply. * Patients with newly diagnosed stage IV NSCLC with an untreated primary must no more than 3 active extracranial metastatic lesions other than the primary site and regional lymph nodes. * Age ≥ 18 years old * Performance Status 0-2 (ECOG) * A signed study specific consent form is required. Lung (only applies to patients with active lung lesions) * Patients cannot have more than 3 lung lesions * Local failure after surgical resection will be consider a metastatic lesion for purposes of protocol inclusion. * All lung lesions must be visible on CT imaging * Cumulative diameter of lung lesions must be \<7cm * Patients may have active mediastinal disease in a single mediastinal nodal station if he/she has not received prior mediastinal RT * Must meet criteria regarding status of primary tumor site described in section 3.1.9. * Must be able to anticipate achieving SBRT dosimetry guidelines * Must have adequate lung function defined within 90 days of enrollment as: (1) Forced Expiratory Volume in 1 second (FEV1) \>30% of predicted or \>800 Ml, (2) diffusing capacity of the lung for carbon monoxide (DLCO) \>30 % predicted and (3) no evidence of actively worsening respiratory status Liver (only applies to patients with active liver lesions * Patients cannot have more than 3 liver lesions * All active liver lesions must be discrete on CT or MRI imaging * Combined diameter of all liver lesions must be \<6cm * Must be able to anticipate achieving SBRT plan per dosimetry guidelines for the liver. * Liver function tests (AST, ALT, total bilirubin) should be within ≤ 3 times the upper limit of normal (ULN) * Serum Albumin must be \>2.5g/dL * Patients cannot have active ascites. Adrenal Gland * Unilateral adrenal disease * Must be able to anticipate achieving the SBRT plan per dosimetry guidelines. Bone Lesions * Treatment of any bone lesion is permissible if it is anticipated that the dosimetry guidelines can be met. Spine and Paraspinal lesions * Patients cannot have more than 3 vertebrae or paraspinal sites involved (each involved vertebral body or paraspinal site is scored as 1 site of disease) * Must be no clinical or radiographic evidence of spinal cord compression * If spinal metastases is within previously irradiated field, there must be a 6 month interval between prior radiation course and study enrollment * Prior spinal cord maximum dose at level of vertebral disease must be ≤50Gy
Exclusion criteria
* Primary tumor progression on first-line chemotherapy * Patients with complete response to first-line chemotherapy with no measurable target for SBRT * \>5 metastatic lesions or \>3 metastatic lesions in patients with an untreated primary site are ineligible (ipsilateral hilar and mediastinal lymph nodes are considered part of an untreated primary site and are not counted as metastatic lesions) * Solitary brain metastases and an untreated node positive primary tumor, without other extracranial metastases amenable to SBRT are ineligible * Retreatment of previously irradiated tumor will be excluded per 3.1.9.2 above. * Mediastinal lymph nodes involving multiple mediastinal nodal stations or N3 disease are ineligible. * Pleural effusion known to be malignant or visible of chest xray. * Untreated brain metastases * Bilateral adrenal metastases * Metastases in other sites not considered amenable to SBRT * Patients with liver metastases cannot have received prior upper abdominal radiation * Prior radiation to spine (most commonly in treatment of primary lung cancer), cannot have received \>50Gy to the spinal cord at the level of current vertebral metastases * Clinical or radiographic evidence of spinal cord compression are ineligible * Patients with serious, uncontrolled, concurrent infection(s). * Weight loss (\>10% of body weight) in the prior 3 months. * Pregnant or lactating women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival | up to 2 years | Actuarial progression-free survival will be determined using the product-limit method of Kaplan and Meier and will be reported with an exact 95% confidence interval. Using the RECIST criteria including progression of the protocol treated tumors, non-protocol treated tumors and the development of new metastatic disease. Only protocol treated tumors will be determined by RECIST defined as complete lesion disappearance or \<25%or original size; partial \>30% decrease of target lesion; stable \<30% decreased of target lesion and; local failure increase \>20% of target lesion. Non-protocol tumor progression will be determined by the treating physician. Measured by imaging every 3 months. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To Assess Physical Function for This Cohort of Patients | up to 3 months after treatment | Using the Vulnerable Elders Survey (VES-13) A 13-item self-reporting questionnaire includes age, self-rated health, limitations in physical function and disability to assess for deterioration of physical function/health. Scoring for the VES-13 is as follows: Total scores are summed together based on self-rated health (0-1), physical function (0-2), functional disability (0-4), (range from 0 to 7). A total score of 3 or more identifies participants as vulnerable to the risk of decline of physical function. |
| Number of Participants With Local Control | up to 2 years | Local control (LC) of SBRT-treated lesions will only be assessed in patients with at least 4-months of radiographic follow-up. |
| Overall Survival | up to 4 years | Overall survival will be reported with an exact 95% confidence interval. |
| Impact of Treatment on Quality of Life (FACT-L) | up to 3 months after treatment | Using the Functional Assessment of Cancer Therapy - Lung (FACT-L) a 36-item self-administered questionnaire evaluating physical, social/family, emotional, and functional well-being; subscales (symptoms, cognitive function, regret of smoking) on a five-point scale from 0 (not at all) to 4 (very much). Maximum score 136. Subscale scores added to obtain total score. The higher the score the greater the impact on the quality of life. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| SBRT for Metastatic NSCLC SBRT for lung lesions, liver lesions, adrenal lesions, spinal lesions
stereotactic body radiation therapy: For lung, liver, axial skeleton, and adrenal tumors a dose of either 54 Gy in 3 fxs or 5000 cGy in 5 fx using SBRT techniques | 27 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Progressed and didn't receive therapy | 2 |
Baseline characteristics
| Characteristic | SBRT for Metastatic NSCLC |
|---|---|
| Age, Continuous | 65 years |
| 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 | 26 Participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 27 |
| other Total, other adverse events | 1 / 27 |
| serious Total, serious adverse events | 0 / 27 |
Outcome results
Primary
Progression-free Survival
Actuarial progression-free survival will be determined using the product-limit method of Kaplan and Meier and will be reported with an exact 95% confidence interval. Using the RECIST criteria including progression of the protocol treated tumors, non-protocol treated tumors and the development of new metastatic disease. Only protocol treated tumors will be determined by RECIST defined as complete lesion disappearance or \<25%or original size; partial \>30% decrease of target lesion; stable \<30% decreased of target lesion and; local failure increase \>20% of target lesion. Non-protocol tumor progression will be determined by the treating physician. Measured by imaging every 3 months.
Time frame: up to 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SBRT for Metastatic NSCLC | Progression-free Survival | 11.2 months |
Secondary
Impact of Treatment on Quality of Life (FACT-L)
Using the Functional Assessment of Cancer Therapy - Lung (FACT-L) a 36-item self-administered questionnaire evaluating physical, social/family, emotional, and functional well-being; subscales (symptoms, cognitive function, regret of smoking) on a five-point scale from 0 (not at all) to 4 (very much). Maximum score 136. Subscale scores added to obtain total score. The higher the score the greater the impact on the quality of life.
Time frame: up to 3 months after treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SBRT for Metastatic NSCLC | Impact of Treatment on Quality of Life (FACT-L) | 100.3 score on a scale | Standard Deviation 23.7 |
Secondary
Number of Participants With Local Control
Local control (LC) of SBRT-treated lesions will only be assessed in patients with at least 4-months of radiographic follow-up.
Time frame: up to 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SBRT for Metastatic NSCLC | Number of Participants With Local Control | 1 Participants |
Secondary
Overall Survival
Overall survival will be reported with an exact 95% confidence interval.
Time frame: up to 4 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SBRT for Metastatic NSCLC | Overall Survival | 28.4 months |
Secondary
To Assess Physical Function for This Cohort of Patients
Using the Vulnerable Elders Survey (VES-13) A 13-item self-reporting questionnaire includes age, self-rated health, limitations in physical function and disability to assess for deterioration of physical function/health. Scoring for the VES-13 is as follows: Total scores are summed together based on self-rated health (0-1), physical function (0-2), functional disability (0-4), (range from 0 to 7). A total score of 3 or more identifies participants as vulnerable to the risk of decline of physical function.
Time frame: up to 3 months after treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SBRT for Metastatic NSCLC | To Assess Physical Function for This Cohort of Patients | 2 Score on a scale | Standard Deviation 2.7 |