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

Not Applicable

Active, not recruiting

• Conditions: Stage III Non-small Cell Lung Cancer
• Interventions: Device: Adaptive Radiotherapy; Device: Non-Adaptive Radiotherapy; Drug: Chemotherapy; Drug: Immunotherapy

• Registration Number: NCT05488626
• Lead Sponsor: Varian, a Siemens Healthineers Company

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 1 month following the end of radiotherapy and will use the Patient Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-08-03
• Study First Submitted QC: 2022-08-03
• Study First Posted: 2022-08-04
• Study Start: 2022-10-20
• Status Verified: 2023-09
• Last Update Submitted: 2023-09-05
• Last Update Posted: 2023-09-06
• Primary Completion: 2024-12
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 244

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Adaptive Arm	Adaptive Radiotherapy	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.
Adaptive Arm	Chemotherapy	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.
Adaptive Arm	Immunotherapy	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.
Non-Adaptive Arm	Non-Adaptive Radiotherapy	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.
Non-Adaptive Arm	Chemotherapy	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.
Non-Adaptive Arm	Immunotherapy	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.

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States