NCT03416972

Brief Summary

Lung cancer is the most common cause of cancer death in Canada. For approximately 30% of patients that present with locally-advanced non-small cell lung cancer (NSCLC), the standard treatment is curative-intent concurrent chemoradiotherapy. Outcomes remain poor, with 5-year survival of only 20%. Despite the long-held belief that higher radiation doses lead to improved overall survival (OS), the landmark randomized trial (RTOG 0617) showed the opposite. The investigators hypothesize that the inferior survival observed may be due to unexpected heart toxicity as secondary analysis revealed that the heart dose was a strong predictor of inferior OS. Up to now, change in heart function is typically detected histologically, requiring autopsy tissue. Therefore, a non-invasive marker of early heart damage is required. Hybrid PET-MRI has become available in Canada only recently. The ability to simultaneously perform metabolic imaging with functional and tissue imaging allows for novel assessment of heart toxicity. The primary objective is to examine the utility of hybrid PET-MRI and DCE-CT to assess acute changes in heart function and to measure inflammation before, and six weeks after NSCLC radiotherapy. A pilot of 20 patients with Stage I-III NSCLC will be enrolled. The findings of this study will aid in the design of new studies to reassess dose escalation for locally advanced NSCLC while limiting the risk of heart toxicity. FDG PET will be used to simultaneously assess both cardiac inflammation and tumour response. Quantitative DCE-CT will also be used to measure ventilation and perfusion changes in the normal lung and tumour after radiotherapy, providing image data that can comprehensively assess both tumour response and potential toxicity in both the heart and lungs. Such information is crucial in understanding the disease and its response to treatment. This data will also aid in the design of radiation techniques that spare the heart in other patients with any thoracic malignancies, including breast cancer, lymphoma, and esophageal cancer.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
20

participants targeted

Target at below P25 for all trials

Timeline
Completed

Started Jan 2018

Typical duration for all trials

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

December 22, 2017

Completed
20 days until next milestone

Study Start

First participant enrolled

January 11, 2018

Completed
20 days until next milestone

First Posted

Study publicly available on registry

January 31, 2018

Completed
1.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2019

Completed
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2020

Completed
Last Updated

January 31, 2018

Status Verified

January 1, 2018

Enrollment Period

1.1 years

First QC Date

December 22, 2017

Last Update Submit

January 24, 2018

Conditions

Outcome Measures

Primary Outcomes (4)

  • Detection of Imaging Biomarkers of acute cardiac inflammation

    FDG-PET imaging to detect increase in cardiac inflammation compared to baseline with corresponding blood markers (Erythrocyte Sedimentation Rate (ESR), high sensitivity C-reactive protein, and troponin levels in blood (inflammation)).

    6 weeks

  • Detection of Imaging Biomarkers of acute cardiac perfusion changes

    DCE-CT imaging to detect changes in acute cardiac perfusion changes compared to baseline.

    6 weeks

  • Detection of Imaging Biomarkers of acute changes in Left-ventricular ejection fraction (LVEF)

    Contrast-enhanced CT imaging to detect acute changes in LVEF compared to baseline.

    6 weeks

  • Detection of cardiac fibrosis

    Gadolinium Enhanced MR imaging to detect cardiac fibrosis compared to baseline

    6 weeks

Secondary Outcomes (4)

  • Tumour Response (metabolism)

    6 weeks

  • Tumour Response (perfusion)

    6 weeks

  • Acute Changes in Lung Ventilation

    6 weeks

  • Acute Changes in Lung Perfusion

    6 weeks

Study Arms (1)

Stage I-III NSCLC patients

Stage I/II NSCLC patients receiving standard stereotactic body radiation therapy and Stage III patients receiving Standard platinum-based chemoradiotherapy will receive PET/MRI, DCE-CT, ECG/EKG, and bloodwork before and six weeks post treatment.

Radiation: Standard platinum-based chemoradiotherapy

Interventions

Stage III patients: Standard platinum-based chemotherapy, total radiation dose 60 Gy in 30 fractions. Stage I/II patients: Standard radiotherapy, total radiation dose of 54 Gy in 3 fractions (peripheral), 55 Gy in 5 fractions (near chest wall), or 60 Gy in 8 fractions (central).

Stage I-III NSCLC patients

Eligibility Criteria

Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

Ultimately, the sample size was based upon practical considerations and that 20 NSCLC patients (10 Stage I/II and 10 Stage III) could be accrued relatively easily from new patient clinics, while sufficiently providing enough evidence to validate the imaging techniques to be used as a non-invasive measure for future clinical trials aimed at reducing or mitigating radiation-induced cardiac toxicity.

You may qualify if:

  • Age 18 or older
  • Ability to provide informed consent
  • Histologically confirmed carcinoma of the lung
  • Stage I-III NSCLC
  • Stage I-II patients to receive 54 Gy in 3 fractions, 55 Gy in 5 fractions, or 60 Gy in 8 fractions (treated every other day)
  • Stage III patient to receive concurrent chemoradiation ( 60 Gy in 30 daily fractions)
  • No prior RT to the thorax
  • ECOG performance status 0-1 within one month of accrual
  • Expected lifespan at least 1 year
  • Negative pregnancy test within one month of accrual if woman is premenopausal
  • Patient presented at multidisciplinary tumor board or quality-assurance rounds
  • Satisfactory pulmonary function tests as determined by the treating radiation oncologist (ie. FEV1 \>= 0.8 for Stage III NSCLC and no threshold for Stage I/II).

You may not qualify if:

  • Patients receiving Prescription RT dose to anything other than LRCP standards for Stage I-III NSCLC.
  • Prior history of atrial fibrillation
  • Previous coronary bypass surgery
  • Patients with severe reversible airways obstruction
  • Patients with acute coronary syndrome (STEMI/non-STEMI and unstable angina)
  • AV block without pacemaker
  • Patients who are renal insufficient (eGFR \<40)
  • Patients with asthma
  • Allergy to iodinated contrast for scans (study subject will be eligible for non-contrast scans)
  • Use of metformin-containing products less than 24 hours prior to CT contrast administration
  • Other contraindications to iodinated contrast media as determined by the research team.
  • Allergy to gadolinium for scans using contrast; will be eligible for non-contrast scans.
  • Other contraindications to gadolinium contrast media as determined by the research team.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Lawson Health Research Institute

London, Ontario, N6C 2R5, Canada

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell LungRadiation Injuries

Condition Hierarchy (Ancestors)

Carcinoma, BronchogenicBronchial NeoplasmsLung NeoplasmsRespiratory Tract NeoplasmsThoracic NeoplasmsNeoplasms by SiteNeoplasmsLung DiseasesRespiratory Tract DiseasesWounds and Injuries

Study Officials

  • Stewart Gaede, PhD

    London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 22, 2017

First Posted

January 31, 2018

Study Start

January 11, 2018

Primary Completion

March 1, 2019

Study Completion

March 1, 2020

Last Updated

January 31, 2018

Record last verified: 2018-01

Data Sharing

IPD Sharing
Will not share

Locations