Clinical trial NCT04455438: SBRT Dose Escalation for Reirradiation of Inoperable Lung Lesions
Official title: Phase I Trial Evaluating Stereotactic Body Radiotherapy (SBRT) Dose Escalation for Reirradiation of Inoperable Lung Lesions
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Non Small Cell Lung Cancer
Lung Metastases
Lead sponsor: Istituto Clinico Humanitas
Sponsor class: OTHER
First posted: 2020-07-02
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: The study is designed to determine the Maximum Tolerated Dose (MTD) that could be safely delivered in the lung reirradiation setting. The MTD was defined as the highest dose level in which a proportion of 1 out of 5 or fewer patients experienced DLT. Due to the late onset nature of DLT, in order to allow for continuous accrual without sacrificing patient safety or the accuracy of identifying the MTD, the Time-To-Event Bayesian Optimal Interval (TITE-BOIN) design will be used.
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: MTD
timeFrame: 5 years
Secondary outcomes:
measure: Other toxicities
timeFrame: 5 years
measure: Overall survival
timeFrame: 5 years
measure: Local control
timeFrame: 5 years
measure: PFS
timeFrame: 5 years
Other outcomes:
Locations:
city: Rozzano
country: Italy
facility: Humanitas Research Hospital
state: Milano
Study officials:
References: