Adaptive Radiation Therapy in Locally Advanced Non-Small Cell Lung Cancer (LARTIA Trial)

Adaptive Radiotherapy in Locally Advanced Non-Small Cell Lung Cancer (LARTIA Trial)



Sponsors


Source

Campus Bio-Medico University

Oversight Info

Has Dmc

No

Is Fda Regulated Drug

No

Is Fda Regulated Device

No


Brief Summary

Anatomical change of tumor during radiotherapy contributes to target missing. However, in the
case of tumor shrinkage, adaptation of volume could result in an increased incidence of
recurrence in the area of target reduction. This study aims to investigate the incidence of
failure of the adaptive approach in Locally Advanced Non-Small Cell Lung Cancer and, in
particular, the risk for local recurrence in the area excluded after replanning.

Detailed Description

Concurrent chemoradiation is the standard of care for patients affected by locally advanced
(LA) NSCLC. Its superiority over radiotherapy alone or sequential chemoradiation has been
proved in multiple phase III randomized trials. In a meta-analysis of six randomized studies,
concurrent chemoradiotherapy decreased locoregional progression by 6.1% at 5 years when
compared with sequential chemoradiation. This resulted in an improvement in overall survival
of 4.5% at 5 years that was possibly directly related to locoregional control. Many patients
however succumb to locoregional failure or distant metastases. Thanks to modern radiotherapy
techniques, some strategies manage the geometrical uncertainties of imaging, treatment
planning, and treatment delivery and thereby improve target coverage with a much steeper dose
gradient and less irradiated normal tissue. The introduction of image-guided radiotherapy
reveals the occurrence of target changes during treatment, and although the percentage of
patients who experienced regression is not high (range 25%-40%), the degree of regression is
in the range of 29% to 40%, corresponding to a rate of tumor shrinkage per fraction of 0.79%
to 1.65%. Anatomical changes during radiotherapy might introduce discrepancies between the
planned and delivered dose. Currently, the literature reports only dosimetric experiences and
lacks clinical data on outcome when patients are treated with the adaptive approach. This
study aims to investigate the failure pattern in patients with LA NSCLC treated with
concurrent chemoradiotherapy with an adaptive approach, in particular, to evaluate the risk
for local recurrence in the area excluded during replanning.

Overall Status

Active, not recruiting

Start Date

2012-11-02

Completion Date

2019-01-20

Primary Completion Date

2017-01-10

Phase

N/A

Study Type

Interventional

Primary Outcome

Measure

Time Frame

Incidence of Local Recurrence and Pattern of Failure
three months

Secondary Outcome

Measure

Time Frame

Response evaluation
three months
Overall Survival
three years
Progression-Free Survival
three years

Enrollment

50

Condition


Intervention

Intervention Type

Radiation

Intervention Name


Description

Patients will be immobilized with customized devices. Either four-dimensional CT or slow CT images using a multislice CT scanner will be acquired to evaluate internal target motion. Initially, gross tumor volume (GTV) will be determined in the maximum intensity projection on the initial size of the tumor and involved lymph nodal sites defined as PET-positive nodes and/or a node diameter greater than 1 cm, clinical target volume (CTV) will be defined as equal to the GTV plus node-positive stations and hilar stations, and planning target volume (PTV) will be created equal to the CTV plus a 0.5-cm safety margin. Treatment will be performed with a linear accelerator in a photon regimen, with a 6-to 15-megavolt (MV) nominal energy and three-dimensional (3D) conformal technique.

Arm Group Label

Radiotherapy Group


Eligibility

Criteria

Inclusion Criteria:

- histologically or cytologically proven NSCLC;

- inoperable stage IIIA/IIIB disease and intrathoracic relapse after surgery;

- positron emission tomography (PET)/computed tomography (CT) and/or total-body CT with
contrast excluding metastatic disease (including brain);

- no previous radiotherapy treatment;

- Eastern Cooperative Oncology Group performance status of 0 to 1;

- clinically measurable/evaluable disease;

- minimum life expectancy of 12 weeks;

- adequate respiratory, renal, hepatic and bone marrow function and non-contraindicative
cardiovascular disease.

Exclusion Criteria:

- previous radiotherapy treatment

- concurrent systemic disorders incompatible with chemotherapy or radiotherapy

Gender

All

Minimum Age

18 Years

Maximum Age

75 Years

Healthy Volunteers

No


Overall Official

Last Name

Role

Affiliation

Sara Ramella, Prof
Study Director
Campus Bio-Medico University

Location

Facility

Michele Fiore
Rome 00128 Italy

Location Countries

Country

Italy


Verification Date

2018-07-01

Lastchanged Date

N/A

Firstreceived Date

N/A

Responsible Party

Responsible Party Type

Principal Investigator

Investigator Affiliation

Campus Bio-Medico University

Investigator Full Name

Michele Fiore

Investigator Title

Researcher, Medical Doctor


Keyword


Has Expanded Access

No

Condition Browse


Number Of Arms

1

Arm Group

Arm Group Label

Radiotherapy Group

Arm Group Type

Experimental

Description

Patients with LA NSCLC treated with concurrent chemoradiation will be enrolled. During treatment all patients will undergo weekly chest CT simulations without intravenous contrast to assess acute toxicity and tumor shrinkage, and they will be all visualized by two radiation oncologists independently. For all CT simulations, each physician will be able to judge whether reduction will be (1) present and clinically significant, (2) present and clinically non significant, or (3) absent. In the case of physician agreement for the first category, a contrast-enhanced CT will be performed to better visualize node reduction, a new target volume will be delineated, and a new treatment plan (replanning study) performed. Patients will be treated without any time break.


Firstreceived Results Date

N/A

Acronym

LARTIA

Patient Data

Sharing Ipd

No


Firstreceived Results Disposition Date

N/A

Study Design Info

Intervention Model

Single Group Assignment

Primary Purpose

Treatment

Masking

None (Open Label)


Study First Submitted

June 27, 2018

Study First Submitted Qc

June 27, 2018

Study First Posted

July 11, 2018

Last Update Submitted

July 10, 2018

Last Update Submitted Qc

July 10, 2018

Last Update Posted

July 12, 2018


ClinicalTrials.gov processed this data on July 12, 2018

Conditions

Conditions usually refer to a disease, disorder, syndrome, illness, or injury. In ClinicalTrials.gov, conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.
Interventions

Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied. Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase

Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions that study is seeking to answer:

In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.

In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.

In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.

In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.

These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.



© 2018 ICH GCP