SBRT Dose Escalation for Reirradiation of Inoperable Lung Lesions (STRILL)

Phase I Trial Evaluating Stereotactic Body Radiotherapy (SBRT) Dose Escalation for Reirradiation of Inoperable Lung Lesions

Prospective phase I study to evaluate the maximum tolerated dose (MTD) of SBRT for thoracic re-irradiation. Dose limiting toxicity will be pneumonitis ≥ G3. The potential advantage of the dose escalation planned in this study is the delivery of an ablative dose to radically treat patients with inoperable local relapse, without unacceptable toxicity.

Study Overview

• Status: Recruiting
• Conditions: Non Small Cell Lung Cancer; Lung Metastases
• Intervention / Treatment: Radiation: SBRT dose escalation

Detailed Description

Radical dose radiotherapy (RT) is frequently used in thoracic malignancies, both for early stage primary non-small cell lung cancer (NSCLC) and for secondary lesions from other primary tumors, particularly in the setting of oligometastatic patients. Although development of distant metastases is the predominant pattern of failure after treatment with radical RT, isolated local recurrences, defined as a tumor recurrence overlapping the 50% isodose field, are still observed and are becoming more and more frequent along with the prolongation of life expectancy in cancer patients. Salvage options for isolated post-radiation local failures are limited, with surgery or retreatment with radiotherapy as potential modalities.

While salvage surgical resection after previous thoracic irradiation has shown encouraging results, most patients experiencing post-radiation local relapse are not surgical candidates. Therefore, reirradiation may be the only viable salvage option for many patients. Retreatment with CFRT has been reported for locoregional failures, with generally-poor outcomes. Although, salvage SBRT after initial CFRT has been described in select small series of heterogeneous patient groups ranging from early stage to locally-advanced and metastatic, few data exist to guide us on the role of reirradiation with SBRT for isolated recurrences after initial SBRT for early-stage NSCLC. Due to the heterogeneity and the low numerosity of these experiences, important questions regarding the safety and efficacy in this setting are still largely unanswered. Particularly, the possibility of delivering a second course of ablative dose RT (BED ≥ 100 Gy) is almost unexplored.

Based on this background, we designed a prospective phase I study to evaluate the maximum tolerated dose (MTD) of SBRT for thoracic re-irradiation. Dose limiting toxicity will be pneumonitis ≥ G3. The potential advantage of the dose escalation planned in this study is the delivery of an ablative dose to radically treat patients with inoperable local relapse, without unacceptable toxicity.

• Study Type: Interventional
• Enrollment (Anticipated): 15
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Davide Franceschini, MD; Phone Number: 0039 028224 7428; Email: davide.franceschini@gmail.com
• Study Contact Backup: Name: Federico Fornasier, M.Sc; Phone Number: 0039 028224 7026; Email: federico.fornasier@gmail.com

Study Locations

• Italy
  • Milano
    • Rozzano, Milano, Italy, 20089
      • Recruiting
      • Humanitas Research Hospital
      • Contact: Davide Franceschini, MD; Phone Number: +39 0282247428; Email: davide.franceschini@humanitas.it
      • Contact: Mauro Loi, MD; Phone Number: +39 0282247461; Email: mauro.loi@humanitas.it

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Inoperable primary non-small cell lung cancer or other metastatic primaries with lung metastases, already treated with radical dose RT;
• Peripheral lesion (> 2 cm from trachea-bronchial tree);
• Inoperable local recurrence (defined as a tumor recurrence overlapping the 50% isodose field) confirmed by documented radiographic findings and/or pathological biopsies within the thoracic area;
• Patients had previously received curative intent RT of more than 50 Gy for conventionally fractionated RT or a biologically equivalent dose of more than 75 Gy for SBRT;
• No active distant metastasis or controlled distant metastasis at the time of re-irradiation

Exclusion Criteria:

• Central or ultra-central lesion(s);
• Incapability of understanding and signing informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SBRT Level 1; The starting dose level will be SBRT 30 Gy in 5 fractions (level 1 or L1).	Radiation: SBRT dose escalation; Re-Stereotactic Body Radiation Therapy (SBRT) with increasing dose levels, from 30 Gy in 5 fractions to 50 Gy in 5 fractions.
Experimental: SBRT Level 2; If the starting dose is tolerated in the first 5 patients, the next dose will be SBRT 40 Gy in 5 fractions (level 2 or L2)	Radiation: SBRT dose escalation; Re-Stereotactic Body Radiation Therapy (SBRT) with increasing dose levels, from 30 Gy in 5 fractions to 50 Gy in 5 fractions.
Experimental: SBRT Level 3; If the second dose is tolerated in the next 5 patients, the next dose will be SBRT 50 Gy in 5 fractions (level 3 or L3)	Radiation: SBRT dose escalation; Re-Stereotactic Body Radiation Therapy (SBRT) with increasing dose levels, from 30 Gy in 5 fractions to 50 Gy in 5 fractions.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MTD	maximal tolerated dose (MTD) of SBRT for thoracic re-irradiation	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Other toxicities	To evaluate acute and late toxicities other than dose limiting toxicity	5 years
Overall survival	To evaluate overall survival of patients undergoing thoracic re-irradiation.	5 years
Local control	To evaluate local control of patients undergoing thoracic re-irradiation.	5 years
PFS	To evaluate progression free survival of patients undergoing thoracic re-irradiation.	5 years

Collaborators and Investigators

• Sponsor: Istituto Clinico Humanitas

Study record dates

Study Major Dates

• Study Start (Actual): May 28, 2020
• Primary Completion (Anticipated): May 1, 2025
• Study Completion (Anticipated): December 1, 2025

Study Registration Dates

• First Submitted: June 29, 2020
• First Submitted That Met QC Criteria: July 1, 2020
• First Posted (Actual): July 2, 2020

Study Record Updates

• Last Update Posted (Actual): September 15, 2022
• Last Update Submitted That Met QC Criteria: September 14, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: 2525

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