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

Phase II Study of Stereotactic Body Radiation Therapy (SBRT) After First-Line Chemotherapy for Metastatic NSCLC

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.

Study Overview

• Status: Completed
• Conditions: Liver Cancer; Non-Small-Cell Lung Carcinoma; Adrenal Cancer
• Intervention / Treatment: Radiation: stereotactic body radiation therapy

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Wilmington, North Carolina, United States, 28401
      • Coastal Carolina Radiation Oncology
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	up to 3 months after treatment
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.	up to 2 years
Overall Survival	Overall survival will be reported with an exact 95% confidence interval.	up to 4 years
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.	up to 3 months after treatment

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences

Publications and helpful links

General Publications

• Petty WJ, Urbanic JJ, Ahmed T, Hughes R, Levine B, Rusthoven K, Papagikos M, Ruiz JR, Lally BE, Chan M, Clark H, D'Agostino RB Jr, Blackstock AW. Long-Term Outcomes of a Phase 2 Trial of Chemotherapy With Consolidative Radiation Therapy for Oligometastatic Non-Small Cell Lung Cancer. Int J Radiat Oncol Biol Phys. 2018 Nov 1;102(3):527-535. doi: 10.1016/j.ijrobp.2018.06.400. Epub 2018 Jul 10.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2010
• Primary Completion (Actual): June 27, 2016
• Study Completion (Actual): June 27, 2016

Study Registration Dates

• First Submitted: August 18, 2010
• First Submitted That Met QC Criteria: August 19, 2010
• First Posted (Estimate): August 20, 2010

Study Record Updates

• Last Update Posted (Actual): November 29, 2019
• Last Update Submitted That Met QC Criteria: November 11, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: lung cancer; SBRT; metastatic; liver; Stereotactic body radiation therapy; spine; adrenal; bone cancer; Spinal Column
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Endocrine System Diseases; Endocrine Gland Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Adrenal Gland Diseases; Carcinoma, Non-Small-Cell Lung; Adrenal Gland Neoplasms
• Other Study ID Numbers: IRB00013994; NCI-2010-01877 (Registry Identifier: CTRP); CCCWFU 62110 (Other Identifier: Wake Forest University Health Sciences)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No