Proton Moderately Hypofractionated Radiotherapy in NSCLC Patients Unable to Tolerate Standard Concurrent Chemoradiotherapy

October 30, 2026 updated by: QI WEIXIANG，MD, Ruijin Hospital

A Prospective Clinical Study of Proton Moderately Hypofractionated Radiotherapy for Non-Small Cell Lung Cancer Patients Unable to Tolerate Standard Concurrent Chemoradiotherapy

The goal of this clinical trial is to learn if proton moderately hypofractionated radiotherapy works to treat non-small cell lung cancer in adults who cannot tolerate standard concurrent chemoradiotherapy. It will also learn about the safety of this treatment. The main questions it aims to answer are: Does proton moderately hypofractionated radiotherapy improve the 1-year overall survival rate compared with historical data from similar patients? What medical problems do participants have during and after this treatment? This is a single-arm study, so all participants will receive proton radiotherapy. Researchers will compare results with historical control data, not with a placebo group. Participants will: Receive proton radiotherapy once daily for about 3 to 4 weeks.

Have checkups and tests before treatment, weekly during treatment, and regularly after treatment. Complete follow-up visits for at least 2 years, including imaging, blood tests, lung function tests, and quality-of-life questionnaires.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
44

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Provision of written informed consent before any study-specific procedure.
  2. Histologically or cytologically confirmed non-small cell lung cancer (NSCLC).
  3. Locally advanced (stage IIIA-IIIC) or oligometastatic NSCLC for which thoracic moderately hypofractionated radiotherapy is planned.
  4. Meets at least one of the following criteria defining inability to tolerate standard concurrent chemoradiotherapy: Frailty/older age: age ≥70 years AND Charlson Comorbidity Index (CCI) ≥1; OR Moderate or worse pulmonary function impairment: GOLD moderate or worse ventilatory impairment (FEV1/FVC <0.70 AND FEV1 ≤80% predicted) OR DLCO ≤60% predicted; OR Interstitial lung disease/pulmonary fibrosis confirmed by high-resolution chest CT or pathology, including idiopathic pulmonary fibrosis (IPF), nonspecific interstitial pneumonia (NSIP), connective tissue disease-associated ILD (CTD-ILD), and other ILD types, AND clinically stable with no evidence of acute exacerbation within the past 3 months.
  5. Age ≥18 years and ≤ 85 years.
  6. Expected survival >6 months.
  7. Assessed by a multidisciplinary team (including radiation oncology, respiratory medicine, and radiology) as having an indication for radiotherapy and being able to tolerate proton therapy.

Exclusion Criteria:

  1. Extensive distant metastasis (non-oligometastatic disease, defined as >5 metastatic lesions or >2 involved organs).
  2. Prior thoracic radiotherapy.
  3. Pregnancy or breastfeeding.
  4. Severe uncontrolled non-neoplastic medical comorbidity (e.g., severe cardiac, hepatic, or renal insufficiency).
  5. History of acute exacerbation of ILD within the past 3 months (confirmed by a respiratory medicine physician).
  6. Active infection or fever.
  7. History of another malignancy within the past 5 years, except adequately treated non-melanoma skin cancer, carcinoma in situ of the cervix, or similar cured malignancies.
  8. Any other condition that, in the investigator's opinion, makes the participant unsuitable for study enrollment.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Proton Moderately Hypofractionated Radiotherapy

All participants will receive thoracic proton moderately hypofractionated radiotherapy as a single-arm intervention. The standard regimen is 54 GyE in 18 fractions (3 GyE per fraction). For patients who cannot meet normal-tissue dose constraints or are at very high risk, prespecified de-escalation to 51 GyE/17 fractions or 48 GyE/16 fractions is permitted; doses below 48 GyE/16 fractions require study withdrawal. Treatment planning prioritizes target coverage (Clinical target volume, CTV V95 ≥95%, Gross tumor volume, GTV V100 ≥100%) while respecting standard organ-at-risk constraints, lymphocyte-sparing organ constraints, and additional esophageal sparing where feasible. Patients with interstitial lung disease receive stricter lung dose limits. No placebo or comparator intervention is administered; outcomes will be compared with historical control data.
Radiation: Proton radiotherapy

Thoracic intensity-modulated proton therapy (IMPT) delivered as moderately hypofractionated radiotherapy. The standard prescription is 54 GyE in 18 fractions (3 GyE per fraction), with protocol-defined de-escalation to 51 GyE/17 fractions or 48 GyE/16 fractions for patients who cannot meet normal-tissue constraints or are at very high risk; doses below 48 GyE/16 fractions are not permitted. This intervention is distinguished from standard photon concurrent chemoradiotherapy by the use of proton therapy, omission of concurrent chemotherapy, a shorter 3-4 week course, and prespecified planning priorities that include target coverage, standard organ-at-risk limits, lymphocyte-sparing organ constraints, and optional esophageal sparing. Patients with interstitial lung disease receive stricter lung dose constraints. IMPT plans are robustly optimized for 3.5% range uncertainty and 3 mm setup uncertainty. No placebo or comparator is

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
1-Year Overall Survival (OS) Rate
Time Frame: 1 year from the start of radiotherapy

Proportion of participants alive at 1 year after initiation of proton radiotherapy. Survival time is defined from the start of radiotherapy to death from any cause or last follow-up; participants lost to follow-up will be censored.
1 year from the start of radiotherapy

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Progression-free survival (PFS)
Time Frame: From start of radiotherapy up to 2 years

Time from start of radiotherapy to disease progression or death from any cause, whichever occurs first.
From start of radiotherapy up to 2 years
Local control (LC)
Time Frame: From start of radiotherapy up to 2 years

Time from start of radiotherapy to imaging-documented progression within the target volume (GTV/CTV).
From start of radiotherapy up to 2 years
Incidence of grade ≥2 radiation pneumonitis
Time Frame: Within 6 months after completion of radiotherapy

Proportion of participants with grade ≥2 radiation pneumonitis according to Common Terminology Criteria for Adverse Events Version (CTCAE) v5.0.
Within 6 months after completion of radiotherapy
Change in pulmonary function
Time Frame: Baseline, and 3, 6, and 12 months after radiotherapy

Change in Forced Expiratory Volume in 1 second(FEV1), Forced Vital Capacity(FVC), and Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO) from baseline to post-radiotherapy assessments.
Baseline, and 3, 6, and 12 months after radiotherapy
Incidence of grade ≥3 lymphopenia
Time Frame: During radiotherapy and up to 3 months after completion of radiotherapy

Proportion of participants with grade ≥3 lymphopenia according to CTCAE v5.0.
During radiotherapy and up to 3 months after completion of radiotherapy
Incidence of grade ≥3 hematologic toxicity
Time Frame: During radiotherapy and up to 3 months after completion of radiotherapy

Proportion of participants with grade ≥3 leukopenia, neutropenia, or thrombocytopenia according to CTCAE v5.0.
During radiotherapy and up to 3 months after completion of radiotherapy

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Incidence of grade ≥3 acute radiotherapy-related adverse events
Time Frame: Within 3 months after completion of radiotherapy

Proportion of participants with any grade ≥3 acute radiotherapy-related adverse event according to CTCAE v5.0.
Within 3 months after completion of radiotherapy
Quality of life - European Organisation for Research and Treatment of Cancer (EORTC)Quality of Life Questionnaire-Core 30 (QLQ-C30)
Time Frame: Baseline, end of radiotherapy (week 4), and 3, 6, and 12 months after radiotherapy.

Change in EORTC QLQ-C30 scores from baseline. The QLQ-C30 is a 30-item questionnaire with multi-item functional scales (physical, role, cognitive, emotional, social) and a global health status/QoL scale, scored from 0 to 100, where higher scores indicate better functioning or better quality of life; and symptom scales/items (fatigue, pain, nausea/vomiting, dyspnoea, insomnia, appetite loss, constipation, diarrhoea, financial impact), scored from 0 to 100, where higher scores indicate greater symptom burden or worse status.
Baseline, end of radiotherapy (week 4), and 3, 6, and 12 months after radiotherapy.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Ruijin Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 30, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 30, 2030

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2030

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 25, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 30, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 5, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 5, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 30, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2026-829

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

This is a small, single-arm, investigator-initiated trial in a rare high-risk population; the informed consent and ethics approval cover only aggregate reporting, and the limited number of participants creates a meaningful risk of re-identification. Only de-identified aggregate results will be reported.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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