Stereotactic Body Radiation Therapy (SBRT) in Metastatic Non-small Cell Lung Cancer

• Sponsor: Wake Forest University Health Sciences (Other)
• Overall Status: Completed
• CT.gov ID: NCT01185639
• Collaborator: (none)
• Enrollment: 29
• Locations: 2
• Arm: 1
• Actual Duration (Months): 70.9
• Patients Per Site: 14.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Non-Small-Cell Lung Carcinoma; Liver Cancer; Adrenal Cancer	Radiation: stereotactic body radiation therapy	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 29 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of Stereotactic Body Radiation Therapy (SBRT) After First-Line Chemotherapy for Metastatic NSCLC
• Actual Study Start Date: Aug 1, 2010
• Actual Primary Completion Date: Jun 27, 2016
• Actual Study Completion Date: Jun 27, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: SBRT for metastatic NSCLC SBRT for lung lesions, liver lesions, adrenal lesions, spinal lesions	Radiation: 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; Other Names: Elekta Bodyframe Cyberknife

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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.

3. Overall Survival [up to 4 years]

   Overall survival will be reported with an exact 95% confidence interval.

4. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 90 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Coastal Carolina Radiation Oncology	Wilmington	North Carolina	United States	28401
2	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157

Sponsors and Collaborators

• Wake Forest University Health Sciences

Investigators

• Principal Investigator: William Blackstock, MD, Wake Forest University Health Sciences

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Wake Forest University Health Sciences
• ClinicalTrials.gov Identifier: NCT01185639
• Other Study ID Numbers: IRB00013994; NCI-2010-01877; CCCWFU 62110
• First Posted: Aug 20, 2010
• Last Update Posted: Nov 29, 2019
• Last Verified: Nov 1, 2019

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Keywords provided by Wake Forest University Health Sciences: lung cancer; metastatic; SBRT; Stereotactic body radiation therapy; liver; spine; adrenal; bone cancer; Spinal Column
• Additional relevant MeSH terms: Carcinoma, Non-Small-Cell Lung; Adrenal Gland Neoplasms

Study Results

Participant Flow

Arm/Group Title	SBRT for Metastatic NSCLC
Arm/Group Description	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
Period Title: Overall Study
STARTED	29
COMPLETED	27
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	SBRT for Metastatic NSCLC
Arm/Group Description	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
Overall Participants	27
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	65
Sex: Female, Male (Count of Participants)
Female	11 40.7%
Male	16 59.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 3.7%
White	26 96.3%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	SBRT for Metastatic NSCLC
Arm/Group Description	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
Measure Participants	27
Median (95% Confidence Interval) [months]	11.2

2. Secondary Outcome

Title	To Assess Physical Function for This Cohort of Patients
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	SBRT for Metastatic NSCLC
Arm/Group Description	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
Measure Participants	27
Mean (Standard Deviation) [Score on a scale]	2 (2.7)

3. Secondary Outcome

Title	Number of Participants With Local Control
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	SBRT for Metastatic NSCLC
Arm/Group Description	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
Measure Participants	27
Count of Participants [Participants]	1 3.7%

4. Secondary Outcome

Title	Overall Survival
Description	Overall survival will be reported with an exact 95% confidence interval.
Time Frame	up to 4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	SBRT for Metastatic NSCLC
Arm/Group Description	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
Measure Participants	27
Median (95% Confidence Interval) [months]	28.4

5. Secondary Outcome

Title	Impact of Treatment on Quality of Life (FACT-L)
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	SBRT for Metastatic NSCLC
Arm/Group Description	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
Measure Participants	27
Mean (Standard Deviation) [score on a scale]	100.3 (23.7)

Adverse Events

Time Frame	90 days following the end of radiation therapy will be recorded and graded on the AE Log. Only those toxicities Grade 3 and above will be reported.
Adverse Event Reporting Description	Only Grade 3 or higher adverse events that were possibly related to stereotactic body radiation therapy were collected for this study.
Arm/Group Title	SBRT for Metastatic NSCLC
Arm/Group Description	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
All Cause Mortality
	SBRT for Metastatic NSCLC
	Affected / at Risk (%)	# Events
Total	0/27 (0%)
Serious Adverse Events
	SBRT for Metastatic NSCLC
	Affected / at Risk (%)	# Events
Total	0/27 (0%)
Other (Not Including Serious) Adverse Events
	SBRT for Metastatic NSCLC
	Affected / at Risk (%)	# Events
Total	1/27 (3.7%)
Injury, poisoning and procedural complications
Rib fracture	1/27 (3.7%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.