Daily Adaptive Radiation Therapy: An Individualized Approach for Stage III Lung Cancer

NCT05488626 | Withdrawn FDA Device

• 1 other identifier: VAR-2021-09
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Stage III Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• Lung cancer specific quality of life

  From randomization to 12 months after completion of chemoradiotherapy

• Global quality of life

  From randomization to 12 months after completion of chemoradiotherapy

• Normal lung tissue radiation exposure

  End of external beam radiation treatment (approximately 2 months from randomization)

• Mean normal tissue doses

  End of external beam radiation treatment (approximately 2 months from randomization)

• Overall response rate

  3 months, 6 months and 12 months after completion of chemoradiotherapy

Study Arms (2)

Adaptive Arm

EXPERIMENTAL

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; Drug: Chemotherapy; Drug: Immunotherapy

Non-Adaptive Arm

ACTIVE COMPARATOR

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.

Device: Non-Adaptive Radiotherapy; Drug: Chemotherapy; Drug: Immunotherapy

Interventions

Non-Adaptive Radiotherapy DEVICE

Standard fractionation external beam radiotherapy (60-66 Gy in 2 Gy/fraction) with daily image guidance.

Non-Adaptive Arm

Chemotherapy DRUG

Concomitant chemotherapy per NCCN or other national guidelines.

Adaptive Arm; Non-Adaptive Arm

Immunotherapy DRUG

Adjuvant immunotherapy per national or institutional guidelines.

Adaptive Arm; Non-Adaptive Arm

Adaptive Radiotherapy DEVICE

Standard fractionation external beam radiotherapy (60-66 Gy in 2 Gy/fraction) with daily online adaptation.

Adaptive Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of signed and dated informed consent form.
• Histologically confirmed NSCLC
• Clinical stage IIIA-IIIB (AJCC v8) disease who are either:
• Patients classified as non-operable by the treatment team
• Patients who refuse surgery
• 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.
• Completed evaluation for metastatic disease with no distant metastases identified. Evaluation must include the following:
• History and physical examination within 30 days prior to enrollment.
• Whole body FDG PET-CT for staging within 60 days prior to enrollment
• Brain MRI or contrast enhanced CT within 60 days prior to enrollment.
• ECOG performance status 0-2 and deemed clinically fit for chemoradiotherapy.
• Age ≥18 years (or at least the local age of consent)
• Patients must have normal organ and marrow function.
• Serum creatinine ≤1.5 mg/dL within 60 days prior to enrollment.
• Measurable disease must be present.

You may not qualify if:

• Contralateral hilar or any supraclavicular/cervical lymph nodes.
• Baseline grade ≥3 dyspnea, or cough, or dysphagia.
• Prior invasive non-skin malignancy unless disease free for a minimum of 3 years.
• History of prior RT to the thorax.
• 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).
• 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.
• Severe active chronic obstructive pulmonary disease or respiratory illness other than NSCLC precluding study therapy.
• Hospitalization for chronic obstructive pulmonary disease or respiratory illness other than NSCLC within 1 year prior to study enrollment.
• Women of childbearing potential and sexually active women not willing or able to use contraception.

Sponsors & Collaborators

• Varian, a Siemens Healthineers Company: lead

Study Sites (1)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Drug Therapy; Immunotherapy

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Immunomodulation; Biological Therapy

Study Officials

• Andrew McDonald, MD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

• Dennis Stanley, PhD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 3, 2022
• First Posted: August 4, 2022
• Study Start: October 20, 2022
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2028
• Last Updated: February 5, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)