SUNSET: SBRT for Ultra-central NSCLC- a Safety and Efficacy Trial

This multi-centre phase I dose-escalation study will use a time-to-event continual reassessment method (TIT-CRM).

Accrual will start at level 1 (60 Gy in 8 fractions). Patients will be assigned to treatment doses using the TITE-CRM model. The model will use all available information from previously accrued patients to assign the highest dose with a predicted risk of grade 3 toxicity of 30% or less.

Study Overview

• Status: Active, not recruiting
• Conditions: Non Small Cell Lung Cancer
• Intervention / Treatment: Radiation: SBRT

Detailed Description

This study will use a time-to-event continual reassessment method (TITE-CRM). The study design is based on RTOG 0813 (described above), but with a more cautious approach, since the patients herein may constitute a high-risk subset of the patients enrolled in RTOG 0813. The modifications include a starting dose (60 Gy in 8 fractions) herein that is lower than the safe dose for central tumors as determined by RTOG 0813 (60 Gy in 5 fractions), and longer follow-up period during which patients are considered at-risk for toxicity, (i.e. two years herein vs. one year in RTOG 0813).

The primary endpoint of this study is the maximally tolerated dose (MTD) of radiotherapy for ultracentral tumors. The MTD is the dose of radiotherapy associated with a <30% rate of grade 3-5 toxicity occurring within 2 years of treatment.

Local Progression, Regional nodal progression, Distant metastases, Progression-Free Survival, Overall survival, patient reported outcomes and quality of life.

The correlative objectives of this study are to determine the prognostic value of ctDNA levels measured pre-treatment, at the end of treatment and 3- and 12-months after treatment.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V8R 6V5
      • BC Cancer -Vancouver Island
  • Ontario
    • London, Ontario, Canada, N6A 4L6
      • London Regional Cancer Program
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Odette Cancer Centre
    • Toronto, Ontario, Canada, M5G 1X6
      • Princess Margaret Cancer Centre
  • Quebec
    • Montreal, Quebec, Canada, H2X 0A9
      • Centre Hospitalier de l'Universite de Montreal (CHUM)
    • Montreal, Quebec, Canada, H4A 3J1
      • McGill University Health Centre-Cedars Cancer Centre
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7S 0B1
      • Saskatoon Cancer Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Pathologically (histologically or cytologically) proven diagnosis of non-small cell lung cancer (NSCLC); if the risk of biopsy is unacceptable, pathologic confirmation is not required providing there is serial growth on serial (>=2) CT imaging and/or FDG avidity that is strongly suggestive of a primary NSCLC.

2. Stage T1-3, N0, M0 (UICC/AJCC Staging, 8th Ed.), tumor size < 6 cm, prior to registration, based upon the following minimum diagnostic workup:

   1. History/physical examination within 4 weeks prior to registration
   2. CT scan with contrast (unless medically contraindicated) within 12 weeks of registration. The CT scan will include the entirety of both lungs, the mediastinum, liver and adrenal glands; the primary tumor dimensions will be measured on CT. Note: Patients with lesions that cannot be visualized by CT scan are not eligible for the study.
   3. Whole body positron emission tomography (PET) scan within 12 weeks of registration, using FDG with adequate visualization of the primary tumor and draining lymph node basins in the hilar and mediastinal regions.
   4. Mediastinal lymph node sampling by any technique is encouraged but not required. Patients with hilar or mediastinal lymph nodes <1 cm and no abnormal hilar or mediastinal uptake on PET will be considered N0. Patients with > 1 cm hilar or mediastinal lymph nodes on CT or abnormal PET (including suspicious but nondiagnostic uptake) may still be eligible if directed tissue biopsies of all abnormally identified areas are negative for cancer.
3. ECOG performance status 0-2;
4. age >18;
5. Ultra-central tumor location: tumours whose planning target volume (PTV) is expected to touch or overlaps the central bronchial tree, esophagus, pulmonary vein, or pulmonary artery as determined at the time of consultation.

Exclusion Criteria:

1. 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.
2. Any prior thoracic radiotherapy.
3. Any prior chemotherapy for the study cancer (cancer proposed to be treated on the study).
4. Prior surgery for the study cancer.
5. Plans for the patient to receive other local therapy (including standard fractionated radiotherapy and/or surgery) while on this study, except at disease progression;
6. Plans for the patient to receive systemic therapy (including standard chemotherapy or biologic targeted agents), while on this study, except at disease progression.
7. Pregnancy.
8. The following autoimmune and connective tissue diseases will be excluded: Scleroderma and Systemic lupus erythematosus
9. patients with interstitial lung disease (ILD).

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: Patients with ultra-central NSCLC T1-3 (<6cm) N0 M0; Level-1 Dose per fraction: 4Gy Number of fractions: 15 Total Dose: 60 Gy Level 0 Dose per fraction: 6Gy Number of fractions: 10 Total Dose: 60 Gy Level 1 Dose per fraction: 7.5 Gy Number of fractions: 8 Total Dose: 60 Gy	Radiation: SBRT; Patients will be assigned to treatment doses using the TITE-CRM model.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximally tolerated dose (MTD)	MTD of radiotherapy for ultracentral tumors. The MTD is the dose of radiotherapy associated with a <30% rate of grade 3-5 toxicity occurring within 2 years of treatment.	Occurring within 2 years of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Local Progression		3-5 years
Regional nodal progression	Defined as presence of enlarged lymph nodes >1 cm [short axis] in the hilum or mediastinum.	3-5 years
Time to distant metastases		3-5 years
Progression-Free Survival		3-5 years
Overall survival		3-5 years
Patient reported outcome	FACT-L	Before treatment & at 3, 6, 9, 12, 18, 24, 36, 48, and 60 months
Quality of Life	EQ-5D-5L	Before treatment & at 3, 6, 9, 12, 18, 24, 36, 48, and 60 months

Collaborators and Investigators

• Sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
• Investigators: Principal Investigator: Meredith Giuliani, MBBS, FRCPC, Princess Margaret Cancer Center

Publications and helpful links

General Publications

• Rosenberg SA, Mak R, Kotecha R, Loo BW Jr, Senan S. The Nordic-HILUS Trial: Ultracentral Lung Stereotactic Ablative Radiotherapy and a Narrow Therapeutic Window. J Thorac Oncol. 2021 Oct;16(10):e79-e80. doi: 10.1016/j.jtho.2021.06.030. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): January 19, 2018
• Primary Completion (Actual): April 19, 2021
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: September 28, 2017
• First Submitted That Met QC Criteria: October 5, 2017
• First Posted (Actual): October 11, 2017

Study Record Updates

• Last Update Posted (Estimated): September 18, 2025
• Last Update Submitted That Met QC Criteria: September 12, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: SUNSET

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No