Clinical trial NCT03485378: Assessment of Precision Irradiation in Early NSCLC and Interstitial Lung Disease
Official title: Assessment of Precision Irradiation in Early NSCLC and Interstitial Lung Disease (ASPIRE-ILD): A Phase II Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Non Small Cell Lung Cancer
Interstitial Lung Disease
Keywords: Stereotactic
Ablative
Radiation
Lead sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
Sponsor class: OTHER
Collaborators: name: London Health Sciences Centre
name: University of British Columbia
name: Western University, Canada
First posted: 2018-04-02
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a prospective phase II study of Stereotactic Ablative Radiotherapy (SABR) in patients with Non-Small Cell Lung Cancer (NSCLC) and co-existent Interstitial Lung Disease (ILD), to determine oncologic and toxicity outcomes. Patients will be divided into 3 separate cohorts based on the ILD-GAP index.

Detailed description: For patients with ILD and concurrent early-stage lung cancer who are not candidates for surgery, data showing high rates of toxicity have led to a difficult clinical dilemma, since there are few alternate treatment options. The option of delivering no treatment whatsoever, which avoids any risk of treatment-related toxicity, is associated with a high risk of death due to the lung cancer itself.

Stereotactic ablative radiotherapy (SABR) is a newer radiotherapy approach which uses modern radiotherapy planning and targeting technologies to precisely deliver larger, ablative doses of radiotherapy. SABR has been associated with high rates of local control. A major advantage of SABR is that in general, the toxicity profile is very favorable, even in patients with substantial co-morbid conditions.

It is possible that currently-used doses and fractionations of SABR, when given with strict planning criteria to minimize the risk of lung toxicity, have only a modest risk of treatment-related toxicity and represent the best possible approach.

This study will examine SABR versus a historical control of untreated stage I non-small cell lung cancer with Overall survival (OS) as the endpoint. OS was selected as it objectively reflects the potential benefits of treatment (i.e. extended survival), the harms of treatment (grade 5 toxicity), and the natural history of the ILD disease process itself.

Eligibility criteria: Inclusion Criteria:

* Stage T1-2, N0, M0 (AJCC Staging, 8th Edition - i.e. tumor size ≤ 5 cm) prior to registration.
* Not a candidate for surgical resection, determined by any of the following:
* Consultation with a thoracic surgeon
* Discussion at Multidisciplinary Team (MDT) rounds with a surgeon present
* Patient refusal of surgery
* Pathologically (histologically or cytologically) proven diagnosis of non-small cell lung cancer (NSCLC) is not required, but strongly recommended.
* If the risk of biopsy is unacceptable, pathologic confirmation is not required providing there is growth over time on Computed Tomography (CT) imaging and/or Fluorodeoxyglucose (FDG) avidity that is strongly suggestive of a primary NSCLC.
* Eastern Cooperative Oncology Group (ECOG) performance status 0-3;
* Age ≥ 18;
* Life expectancy \> 6 months
* Fibrotic interstitial lung disease of any subtype, as diagnosed by a respirologist/pulmonologist.

Exclusion Criteria:

* Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 2 years (e.g., carcinomas in situ of the breast, oral cavity, or cervix are permissible); previous lung cancer, if the patient is disease-free for a minimum of 2 years is permitted.
* Prior thoracic radiotherapy
* Plans for the patient to receive other local therapy while on this study, except at disease progression;
* Plans for the patient to receive systemic therapy (including standard chemotherapy or biologic targeted agents), while on this study, except at disease progression. Patients are allowed to receive anti-fibrotic agents used in the treatment of IPF or non-IPF fibrotic ILD (e.g. nintedanib, pirfenidone), or steroids, if those are part of their current ILD treatment regimen. Other immunosuppressive drugs such as mycophenolate, azathioprine, cyclophosphamide, and rituximab must be stopped for 2 weeks prior and 2 weeks after treatment.
* Active pregnancy
* Concurrent administration of any drugs with known radiosensitive effects (e.g. Methotrexate).

Primary outcomes:
measure: Overall Survival
timeFrame: 4 years
Secondary outcomes:
measure: Toxicity as measured by the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
timeFrame: 8 years
measure: Progression-Free Survival
timeFrame: 8 years
measure: Local Control as determined via radiographic evidence
timeFrame: 8 years
measure: Cough Severity as reported by the participant via 10 cm analogue Cough Severity Scale
timeFrame: 8 years
measure: Rates of Acute-Exacerbation of Idiopathic Pulmonary Fibrosis (IPF)
timeFrame: 8 years
measure: Rates of Acute-Exacerbation of ILD
timeFrame: 8 years
measure: Quality of Life measured by the Functional Assessment of Cancer Therapy - Lung questionnaire
timeFrame: 8 years
measure: Changes in ILD Severity measured by High Resolution Computed Tomography (HRCT)
timeFrame: 8 years
measure: Changes in Pulmonary Function Tests
timeFrame: 8 years
measure: Exploratory Quantitative Analysis of High Resolution Computed Tomography (HRCT) Features
timeFrame: 8 years
measure: Analysis of Outcomes for Patients Eligible for Study Who Decline Radiotherapy
timeFrame: 8 years
measure: Quality of Life measured by the EuroQOL Group EQ-5D-5L questionnaire
timeFrame: 8 years
Other outcomes:
Locations:
city: Edmonton
country: Canada
facility: Alberta Health Services, Cross Cancer Institude
state: Alberta
city: London
country: Canada
facility: London Regional Cancer Program of the Lawson Health Research Institute
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: UHN Princess Margaret Cancer Centre
state: Ontario
city: Montréal
country: Canada
facility: CHUM Université de Montréal
state: Quebec
city: Edinburgh
country: United Kingdom
facility: Edinburgh Cancer Centre, Western General Hospital
Study officials:
affiliation: London Health Sciences Centre, Lawson Health Research Institute
name: David Palma, MD
role: STUDY_CHAIR
affiliation: London Health Sciences Centre, Lawson Health Research Institute
name: Alexander Louie, MD
role: STUDY_CHAIR
affiliation: University of British Columbia
name: Chris Ryerson, MD
role: STUDY_CHAIR
References:
citation: Palma DA, Chen H, Bahig H, Gaede S, Harrow S, Laba JM, Qu XM, Rodrigues GB, Yaremko BP, Yu E, Louie AV, Dhaliwal I, Ryerson CJ. Assessment of precision irradiation in early non-small cell lung cancer and interstitial lung disease (ASPIRE-ILD): study protocol for a phase II trial. BMC Cancer. 2019 Dec 11;19(1):1206. doi: 10.1186/s12885-019-6392-8.