Clinical trial NCT02433574: Locally Invasive NSCLC Treated With NEo-Adjuvant Stereotactic Body RadioTherapy and REsection
Official title: Phase I Study: Locally Invasive NSCLC Treated With NEo-Adjuvant Stereotactic Body Radiotherapy and REsection
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Non-Small-Cell Lung Cancer
Carcinoma
Keywords: radiosurgery
Neoadjuvant Therapy
Lead sponsor: Juravinski Cancer Center
Sponsor class: OTHER
First posted: 2015-05-05
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Despite improved staging and operative techniques, the rate of incomplete resection (R1) of NSCLC has remained significant over the last decades. Patients with R1 resection have significantly worse survival compared to those with complete resection (R0).

This is a phase I study that investigates the feasibility and safety of delivering Stereotactic Body Radiotherapy (SBRT) to patients with locally invasive NSCLC (cT3-4, N0-1) who are at risk for incomplete resection.

Twenty patients with NSCLC will be treated with SBRT followed by surgery and appropriate adjuvant therapy. Patients will be divided into groups, of 5 patients each, treated with escalating doses (35, 40, 45 and 50 Gy) in 10 daily fractions.

The primary outcome is the feasibility i.e. the ability to complete safely SBRT and surgery (within 6 weeks). Secondary outcomes include acute and late adverse events, R0/R1/R2 rates and secondary surrogates of feasibility.

If successful, this study will lead to further evaluation of pre-operative SBRT in NSCLC.


Eligibility criteria: Inclusion Criteria:

* Patients will be included if they are aged 18 years or older,
* with biopsy proven NSCLC,
* clinically staged T3-T4 marginally resectable i.e. deemed at risk to achieve \<R0 resection (such as invasion of critical mediastinal or hilar structures, nodal extra-capsular extension, chest wall, vertebral bodies, compromised bronchial stump margin, based on CT images of the chest).
* Patients also need to be pathologically staged N0-1 disease,
* with an SBRT CTV≤200cm3, based on planning CT images.
* ECOG status is required to be \<2 within 4 weeks prior to registration and
* patients must be deemed medically operable by the surgical team.

Exclusion Criteria:

* Patients will be excluded if they are deemed medically inoperable by the surgical team
* and have a weight loss of ≥10% within 3 months prior to pathological diagnosis.
* Patients will also have no absolute contraindication to RT such as connective tissue disease, pacemaker-dependent patient with the pacemaker receiving higher than tolerance dose, had no had previous RT to the current region of the study, that would result in overlap of RT fields,
* patients must have no plans to receive other local therapy while on study, except at disease progression,
* patients have not had other malignancy within 2 years prior to the study (other than non-melanomatous skin cancers)

Primary outcomes:
measure: Feasibility of SBRT followed by surgery (proportion of patients who can undergo 10 fractions of SBRT followed by Surgery)
timeFrame: 18 months
Secondary outcomes:
measure: Early safety of SBRT-S through collection of serious adverse events (CTCAE version 4.0 grade 3 or higher) from beginning of SBRT to 4 weeks after completion of surgery.
timeFrame: 18 months
measure: Late safety profile of SBRT-S through collection of surgical complication rates assessed at 6 and 18 months post-registration (thus 30 months from opening of the study, assuming it takes 1 year to complete accrual).
timeFrame: 30 months
measure: Secondary feasibility outcomes (including accrual rate, consent rate, rates of deviation from scheduled treatment plan, and reasons for delay)
timeFrame: 18 months
measure: Pathological response following neoadjuvant SBRT (proportion of R0, R1 and R2 resections)
timeFrame: 18 months
measure: Pathologic changes associated with neo-adjuvant SBRT with analysis of irradiated tissues
timeFrame: 18 months
Other outcomes:
Locations:
city: Hamilton
country: Canada
facility: Juravinski Cancer Centre
state: Ontario
Study officials:
affiliation: Juravinski Cancer Center
name: Theodoros Tsakiridis, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Nguyen NA, Isfahanian N, Pond G, Hanna W, Cutz JC, Wright J, Swaminath A, Shargall Y, Chow T, Wierzbicki M, Okawara G, Quan K, Finley C, Juergens R, Tsakiridis T. A Novel Neoadjuvant Therapy for Operable Locally Invasive Non-Small-Cell Lung Cancer. Phase I Study of Neoadjuvant Stereotactic Body Radiotherapy. LINNEARRE I (NCT02433574). Clin Lung Cancer. 2017 Jul;18(4):436-440.e1. doi: 10.1016/j.cllc.2017.01.007. Epub 2017 Jan 31.