Daily Adaptive Radiation Therapy: An Individualized Approach for Stage III Lung Cancer (ARTIA-Lung)

Daily Adaptive vs Non-Adaptive External Beam Radiation Therapy With Concurrent Chemotherapy for Locally Advanced Non-Small Cell Lung Cancer: A Prospective Randomized Trial of an Individualized Approach for Toxicity Reduction (ARTIA-Lung)

This is a prospective multi-center randomized clinical trial designed to demonstrate that daily online adaptive radiotherapy with concomitant chemotherapy for stage III non-small cell lung cancer (NSCLC) will result in decreased acute respiratory and esophageal toxicity compared with non-adaptive radiotherapy with concomitant chemotherapy. The timepoint for this assessment will be 3 months following the end of radiotherapy and will use the Patient Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE).

Study Overview

• Status: Withdrawn
• Conditions: Stage III Non-small Cell Lung Cancer
• Intervention / Treatment: Device: Adaptive Radiotherapy; Drug: Chemotherapy; Drug: Immunotherapy; Device: Non-Adaptive Radiotherapy

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Provision of signed and dated informed consent form.
2. Histologically confirmed NSCLC

3. Clinical stage IIIA-IIIB (AJCC v8) disease who are either:

   1. Patients classified as non-operable by the treatment team
   2. Patients who refuse surgery
4. Clinical stage IIIC due to contralateral mediastinal lymph node involvement only (e.g., no contralateral hilar or any supraclavicular/cervical lymph node metastases). Mediastinal stations 2R and 4R are considered contralateral for patients whose primary tumor is within the left lung. Mediastinal stations 2L, 4L, 5, and 6 are considered contralateral for patients whose primary tumor is in the right lung.

5. Completed evaluation for metastatic disease with no distant metastases identified. Evaluation must include the following:

   1. History and physical examination within 30 days prior to enrollment.
   2. Whole body FDG PET-CT for staging within 60 days prior to enrollment
   3. Brain MRI or contrast enhanced CT within 60 days prior to enrollment.
6. ECOG performance status 0-2 and deemed clinically fit for chemoradiotherapy.
7. Age ≥18 years (or at least the local age of consent)
8. Patients must have normal organ and marrow function.
9. Serum creatinine ≤1.5 mg/dL within 60 days prior to enrollment.
10. Measurable disease must be present.
11. Negative urine or serum pregnancy test within 14 days prior to enrollment for women of childbearing potential.

Exclusion Criteria:

1. Contralateral hilar or any supraclavicular/cervical lymph nodes.
2. Baseline grade ≥3 dyspnea, or cough, or dysphagia.
3. Prior invasive non-skin malignancy unless disease free for a minimum of 3 years.
4. History of prior RT to the thorax.
5. Severe imaging artifact that, in the view of the local investigator, would preclude accurate identification of the thoracic anatomy and tumor targets on the cone beam CT (e.g., artifact created implanted cardiac device in proximity to the targets).
6. Evidence of malignant pleural effusion, defined as either FDG PET avidity within effusion fluid or presence of malignant cells identified by cytology of thoracentesis fluid.
7. Severe active chronic obstructive pulmonary disease or respiratory illness other than NSCLC precluding study therapy.
8. Hospitalization for chronic obstructive pulmonary disease or respiratory illness other than NSCLC within 1 year prior to study enrollment.
9. Women of childbearing potential and sexually active women not willing or able to use contraception.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Adaptive Arm; Subjects in this arm will receive their external beam radiotherapy on the Ethos Radiotherapy System version 2.0 with HyperSight cone beam computed tomography imaging, with daily online adaptation of their radiation dosimetry plan to account for day-to-day changes in the tumor and surrounding anatomical structures. All subjects will received standard concurrent chemotherapy and may receive adjuvant immunotherapy, if indicated.	Device: Adaptive Radiotherapy; Standard fractionation external beam radiotherapy (60-66 Gy in 2 Gy/fraction) with daily online adaptation.; Drug: Chemotherapy; Concomitant chemotherapy per NCCN or other national guidelines.; Drug: Immunotherapy; Adjuvant immunotherapy per national or institutional guidelines.
Active Comparator: Non-Adaptive Arm; Subjects in this arm will receive their radiotherapy using standard image-guided radiation therapy (IMRT) techniques. All subjects will receive standard concurrent chemotherapy and may receive adjuvant immunotherapy, if indicated.	Drug: Chemotherapy; Concomitant chemotherapy per NCCN or other national guidelines.; Drug: Immunotherapy; Adjuvant immunotherapy per national or institutional guidelines.; Device: Non-Adaptive Radiotherapy; Standard fractionation external beam radiotherapy (60-66 Gy in 2 Gy/fraction) with daily image guidance.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute toxicity	Composite rate of any increase in cough, or dyspnea, or dysphagia scores by 1+ using PRO-CTCAE.	From randomization to 90 days after completion of chemoradiotherapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lung cancer specific quality of life	Results from the FACT-L questionnaire	From randomization to 12 months after completion of chemoradiotherapy
Global quality of life	Results from the EQ-5D-5L questionnaire	From randomization to 12 months after completion of chemoradiotherapy
Normal lung tissue radiation exposure	The percentage of normal lung tissue volume that receives radiation of 20 Gy or more over the course of radiation treatment.	End of external beam radiation treatment (approximately 2 months from randomization)
Mean normal tissue doses	Mean dose delivered to the heart, esophagus and normal lung tissue over the course of radiation treatment.	End of external beam radiation treatment (approximately 2 months from randomization)
Overall response rate	Frequency of complete and partial tumor response as determined on chest imaging using RECIST v1.1	3 months, 6 months and 12 months after completion of chemoradiotherapy
Local progression	Physician report of progression determined by imaging or clinical evaluation	12 months after completion of chemoradiotherapy
Radiation pneumonitis	CTCAE v.5.0 grade 2+ pneumonitis	12 months after completion of chemoradiotherapy
Healthcare resource utilization	Hospitalizations, emergency department visits, advanced medical or imaging procedures associated with the treatment of CTCAE grade 2+ adverse events related to EBRT.	From the start of radiation treatment to 12 months after completion of chemoradiotherapy.

Collaborators and Investigators

• Sponsor: Varian, a Siemens Healthineers Company
• Investigators: Principal Investigator: Andrew McDonald, MD, University of Alabama at Birmingham; Principal Investigator: Dennis Stanley, PhD, University of Alabama at Birmingham

Study record dates

Study Major Dates

• Study Start (Actual): October 20, 2022
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: August 3, 2022
• First Submitted That Met QC Criteria: August 3, 2022
• First Posted (Actual): August 4, 2022

Study Record Updates

• Last Update Posted (Actual): February 5, 2026
• Last Update Submitted That Met QC Criteria: February 2, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Therapeutics; Biological Therapy; Immunomodulation; Drug Therapy; Immunotherapy
• Other Study ID Numbers: VAR-2021-09

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No