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

Primary Purpose

Non-Small-Cell Lung Cancer, Carcinoma

Status

Unknown status

Phase

Not Applicable

Locations

Canada

Study Type

Interventional

Intervention

Neoadjuvant Stereotactic body radiation (SBRT)

About this trial

This is an interventional treatment trial for Non-Small-Cell Lung Cancer focused on measuring radiosurgery, Neoadjuvant Therapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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)

Sites / Locations

Juravinski Cancer CentreRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Neoadjuvant stereotactic body radiation

Arm Description

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.

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

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.

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).

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)

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.

Pathologic changes associated with neo-adjuvant SBRT with analysis of irradiated tissues

Full Information

NCT ID

NCT02433574

First Posted

February 4, 2015

Last Updated

July 16, 2018

Sponsor

Juravinski Cancer Center

1. Study Identification

Unique Protocol Identification Number

NCT02433574

Brief Title

Locally Invasive NSCLC Treated With NEo-Adjuvant Stereotactic Body RadioTherapy and REsection

Acronym

LINNEARRE-I

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2018

Overall Recruitment Status

Unknown status

Study Start Date

November 2015 (undefined)

Primary Completion Date

January 2019 (Anticipated)

Study Completion Date

January 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Juravinski Cancer Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Non-Small-Cell Lung Cancer, Carcinoma

Keywords

radiosurgery, Neoadjuvant Therapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Neoadjuvant stereotactic body radiation

Arm Type

Experimental

Arm Description

Intervention Type

Radiation

Intervention Name(s)

Neoadjuvant Stereotactic body radiation (SBRT)

Intervention Description

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.

Primary Outcome Measure Information:

Title

Feasibility of SBRT followed by surgery (proportion of patients who can undergo 10 fractions of SBRT followed by Surgery)

Description

Time Frame

18 months

Secondary Outcome Measure Information:

Title

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.

Time Frame

18 months

Title

Description

Complications recorded include incidence of bronchopleural fistula, esophageal fistula, wound healing complications (dehiscence, infection) and post-operative pulmonary complications).

Time Frame

30 months

Title

Secondary feasibility outcomes (including accrual rate, consent rate, rates of deviation from scheduled treatment plan, and reasons for delay)

Description

These include accrual rate, consent rate, rates of deviation from scheduled treatment plan of 6 weeks, and reasons for delay)

Time Frame

18 months

Title

Pathological response following neoadjuvant SBRT (proportion of R0, R1 and R2 resections)

Description

To determine the proportion of R0, R1 and R2 resections after neoadjuvant SBRT.

Time Frame

18 months

Title

Pathologic changes associated with neo-adjuvant SBRT with analysis of irradiated tissues

Time Frame

18 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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)

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Clinical Trials Department Juravinski Cancer Center

Phone

905-387-9495

First Name & Middle Initial & Last Name or Official Title & Degree

Naghmeh Isfahanian, MD

Phone

9053879495

isfahanian@hhsc.ca

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Theodoros Tsakiridis, M.D., Ph.D.

Organizational Affiliation

Juravinski Cancer Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Juravinski Cancer Centre

City

Hamilton

State/Province

Ontario

ZIP/Postal Code

L8V 5C2

Country

Canada

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Theos Tsakiridis, MD PhD

Phone

905-308-3574

Ext

64704

tsakirid@HHSC.CA

12. IPD Sharing Statement

Citations:

PubMed Identifier

28215851

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.

Results Reference

derived

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Locally Invasive NSCLC Treated With NEo-Adjuvant Stereotactic Body RadioTherapy and REsection

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