Clinical trial NCT01185639: Stereotactic Body Radiation Therapy (SBRT) in Metastatic Non-small Cell Lung Cancer
Official title: Phase II Study of Stereotactic Body Radiation Therapy (SBRT) After First-Line Chemotherapy for Metastatic NSCLC
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Non-Small-Cell Lung Carcinoma
Liver Cancer
Adrenal Cancer
Keywords: lung cancer
metastatic
SBRT
Stereotactic body radiation therapy
liver
spine
adrenal
bone cancer
Spinal Column
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
First posted: 2010-08-20
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Progression-free Survival
timeFrame: up to 2 years
Secondary outcomes:
measure: To Assess Physical Function for This Cohort of Patients
timeFrame: up to 3 months after treatment
measure: Number of Participants With Local Control
timeFrame: up to 2 years
measure: Overall Survival
timeFrame: up to 4 years
measure: Impact of Treatment on Quality of Life (FACT-L)
timeFrame: up to 3 months after treatment
Other outcomes:
Locations:
city: Wilmington
country: United States
facility: Coastal Carolina Radiation Oncology
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
Study officials:
affiliation: Wake Forest University Health Sciences
name: William Blackstock, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.