Locally Invasive NSCLC Treated With NEo-Adjuvant Stereotactic Body RadioTherapy and REsection (LINNEARRE-I)

Phase I Study: Locally Invasive NSCLC Treated With NEo-Adjuvant Stereotactic Body Radiotherapy and REsection

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.

Study Overview

• Status: Unknown
• Conditions: Carcinoma; Non-Small-Cell Lung Cancer
• Intervention / Treatment: Radiation: Neoadjuvant Stereotactic body radiation (SBRT)

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • Recruiting
      • Juravinski Cancer Centre
      • Contact: Theos Tsakiridis, MD PhD; Phone Number: 64704 905-308-3574; Email: tsakirid@HHSC.CA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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)

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: Neoadjuvant stereotactic body radiation; Single arm study. Four cohorts of 5 patients will undergo neo-adjuvant SBRT for lung cancer. Eligible patients will have operable, borderline resectable lung cancer , they will be treated with SBRT, prior to undergoing surgical resection.

Radiation: Neoadjuvant Stereotactic body radiation (SBRT); Dose escalation of neo-adjuvant SBRT in operable patients with locally advanced non-small cell lung cancer. The first cohort will be treated with a dose of 35 Gy in 10 fractions, the second cohort will be treated with a dose of 40 Gy in 10 fractions, the third cohort will be treated with a dose of 45 Gy in 10 fractions, the fourth cohort will be treated with a dose of 50 Gy in 10 fractions. The SBRT doses will be escalated only once all patients in the previous cohort will have completed safely their treatments.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of SBRT followed by surgery (proportion of patients who can undergo 10 fractions of SBRT followed by Surgery)	Feasibility of neo-adjuvant SBRT followed by surgery. This will be measured as the proportion of patients who can undergo 10 fractions of SBRT followed by Surgery as scheduled (within 6 weeks from registration).	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.		18 months
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).	Complications recorded include incidence of bronchopleural fistula, esophageal fistula, wound healing complications (dehiscence, infection) and post-operative pulmonary complications).	30 months
Secondary feasibility outcomes (including accrual rate, consent rate, rates of deviation from scheduled treatment plan, and reasons for delay)	These include accrual rate, consent rate, rates of deviation from scheduled treatment plan of 6 weeks, and reasons for delay)	18 months
Pathological response following neoadjuvant SBRT (proportion of R0, R1 and R2 resections)	To determine the proportion of R0, R1 and R2 resections after neoadjuvant SBRT.	18 months
Pathologic changes associated with neo-adjuvant SBRT with analysis of irradiated tissues		18 months

Collaborators and Investigators

• Sponsor: Juravinski Cancer Center
• Investigators: Principal Investigator: Theodoros Tsakiridis, M.D., Ph.D., Juravinski Cancer Center

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: November 1, 2015
• Primary Completion (Anticipated): January 1, 2019
• Study Completion (Anticipated): January 1, 2019

Study Registration Dates

• First Submitted: February 4, 2015
• First Submitted That Met QC Criteria: April 29, 2015
• First Posted (Estimate): May 5, 2015

Study Record Updates

• Last Update Posted (Actual): July 17, 2018
• Last Update Submitted That Met QC Criteria: July 16, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: radiosurgery; Neoadjuvant Therapy
• 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: LINNEARRE-I

Drug and device information, study documents

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