Pulmonary Magnetic Resonance-guided Online Adaptive Radiotherapy of Locally Advanced Non-Small Cell Lung Cancer (PUMA)

March 6, 2026 updated by: Juergen Debus, University Hospital Heidelberg
MR-guided radiotherapy is an innovative technique which supports sophisticated approaches towards pulmonary adaptive radiotherapy (ART). Such individualized treatment approaches can lead to reduced toxicity and potentially better local tumor control for patients with LA-NSCLC in the future. PUMA is an early clinical trial, which aims to demonstrate the feasibility of MR-guided online ART to locally-advanced NSCLC. In a second step, the investigators aim to use the data from this feasibility trial to design and launch a further phase I/II clinical study that directly compares the benefits of MR-guided online ART of LA-NSCLC to CT-based (A)RT approaches.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

Non-small cell lung cancer (NSCLC) is very common and carries the highest mortality of all malignant diseases (350.000 - 400.000 deaths per year in the European Union). In specific, the 5-year overall survival rate of locally-advanced NSCLC (LA-NSCLC) is merely 20%. One reason for this dismal prognosis is the lack of effective treatment options. Since most patients with LA-NSCLC are not candidates for a tumor resection, definitive (chemo)radiotherapy (C)RT with consecutive immunotherapy (IT) is the treatment of choice according to national and international guidelines. However, local tumor relapse remains a major pattern of recurrence in approx. 30% of cases. Furthermore, many patients cannot benefit from chemotherapy due to multiple comorbidities, and application of IT requires an initial tumor response to (C)RT and absence of higher-grade pulmonary toxicity. Consequently, radiotherapy is a cornerstone in the locally ablative treatment of LA-NSCLC and essentially influences the course of the further treatment. MR-guided radiotherapy is an innovative technique which supports sophisticated approaches towards pulmonary adaptive radiotherapy (ART). Such adaptive radiation approaches allow highly individualized thoracic radiotherapy with dose distributions tailored to the interfractional changes in tumor geometry and anatomy of surrounding OARs. Therefore, MR-guided ART has the potential to optimize the balance between intensified target volume dose and sparing of vulnerable OARs. This prospective, multicenter clinical trial is desinged to demonstrate the clinical feasibility and gain first data on the safety of MR-guided online ART to LA-NSCLC. Based on the investigators extensive experience with MR-guided RT of early-stage NSCLC and lung metastases, the invesitgators hypothesize that MR-guided online ART to LA-NSCLC can be performed successfully in ≥ 80% of patients with a mean time < 90 minutes. The investigators plan to include 30 patients with LA-NSCLC in Union for International Cancer Control (UICC) stage IIIA-C at three German university hospitals (Uniklinikum Heidelberg, Uniklinikum LMU München, Uniklinikum Tübingen). Patients will receive MR-guided online ART, which includes gated dose delivery as well as online plan adaptation once weekly or in case major anatomical changes are detected on daily MR-imaging. Patients will be followed-up to assess toxicity, tumor control (by means of thoracic CT- and MR-imaging) and patient-reported outcomes for 24 months after treatment.

Study Type

Interventional

Enrollment (Estimated)

30

Phase

  • Not Applicable

Contacts and Locations

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

Study Locations

  • Germany
      • Heidelberg, Germany, 69120
        • University Hospital of Heidelberg, Radiation Oncology
    • Baden-Wurttemberg
      • Tübingen, Baden-Wurttemberg, Germany, 72076
        • Universitätsklinikum Tübingen
    • Bavaria
      • Münich, Bavaria, Germany, 81377
        • Ludwig-Maximilian-Universität München

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

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Histologically-proven non-small cell lung cancer (NSCLC)
  • Stage III A - C according to the 8th edition of the Union for International Cancer Control (UICC) TNM classification
  • Indication for definitive thoracic chemoradiotherapy
  • Age ≥ 18 years
  • ECOG 0 - 2
  • Adequate pulmonary function for chemoradiotherapy confirmed by a current pulmonary function test (≤ 6 weeks from treatment start)
  • Ability to lie still on the MR-linac table for at least one hour
  • Ability to hold one's breath for at least 20 seconds
  • Successful completion of an MR-guided treatment simulation
  • For women with childbearing potential: adequate contraception
  • Ability of the patient to understand character and individual consequences of the clinical trial
  • Written informed consent (must be available before enrolment in the trial)

Exclusion Criteria:

  • Involvement of supraclavicular lymph nodes (supraclavicular N3)
  • Additional pulmonary lesions (T3 - 4 due to additional lesion in the same or another lobe)
  • Previous radiotherapy of the lung and mediastinum, if previous and current target volumes overlap
  • Patients who have not yet recovered from acute toxicities of prior therapies
  • Contraindications against performing MRI scans (e.g. pacemakers or other implants making MRI impossible)
  • Pregnant or lactating women
  • Participation in another competing clinical study or observation period of competing trials
  • Refusal of the patients to take part in the study

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
Intervention / Treatment
Experimental: MR-guided adaptive radiotherapy
Patients receive Photon radiotheray as an MR-guided adaptive radiotherapy
Radiation: Photons
MR-guided adaptive radiotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
clinical feasibility -1-
Time Frame: through study completion, an average of 2 years
successfully completed online adapted RT fractions
through study completion, an average of 2 years
clinical feasibility -2-
Time Frame: through study completion, an average of 2 years
treatment time for online adapted RT fractions
through study completion, an average of 2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
acute side effects
Time Frame: 3 months from treatment start
changes in toxicity according to CTCAE V5.0
3 months from treatment start
subacute side effect
Time Frame: 6 months from treatment start
changes in toxicity according to CTCAE V5.0
6 months from treatment start
chronic side effect
Time Frame: through study completion, at least 24 months
changes in toxicity according to CTCAE V5.0
through study completion, at least 24 months
Local tumor control
Time Frame: through study completion, at least 24 months
time from treatment start until in-field tumor recurrence
through study completion, at least 24 months
Progession free survival
Time Frame: through study completion, at least 24 months
time from treatment start until death or progression of tumor disease
through study completion, at least 24 months
Overall survival
Time Frame: through study completion, at least 24 months
time from treatment start until death
through study completion, at least 24 months
Longitudinal pulmonary function
Time Frame: through study completion, at least 24 months
changes in forced exspiratory volume in 1st second (FEV1s), vital capacity (vc), etc.
through study completion, at least 24 months

Collaborators and Investigators

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

Sponsor

University Hospital Heidelberg

Collaborators

Ludwig-Maximilians - University of Munich
German Cancer Research Center
University Hospital Tuebingen

Investigators

  • Principal Investigator: Juergen Debus, Prof, University Hospital Heidelberg

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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 (Actual)

June 23, 2022

Primary Completion (Estimated)

March 1, 2027

Study Completion (Estimated)

March 1, 2028

Study Registration Dates

First Submitted

January 13, 2022

First Submitted That Met QC Criteria

February 2, 2022

First Posted (Actual)

February 14, 2022

Study Record Updates

Last Update Posted (Actual)

March 9, 2026

Last Update Submitted That Met QC Criteria

March 6, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RadOnk-PUMA_2021

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

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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