Non Small Cell Lung CancerPhase 1PROMISENCT06622174
Pulse Radiotherapy to Overcome Metastatic Immune System Evasion in Lung Cancer
A Phase 1 study testing Pulse radiotherapy in people with Non Small Cell Lung Cancer and Metastatic Lung Cancer, run by Centre hospitalier de l'Université de Montréal (CHUM) at 1 site in Canada.
Trial summary
This phase I study aims to evaluate the safety and effectiveness of adaptive pulsed radiotherapy combined with immunotherapy in patients with metastatic non-small cell lung cancer (NSCLC) resistant to immune checkpoint inhibitors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non Small Cell Lung Cancer, Metastatic Lung Cancer
- What is being tested?
- Pulse radiotherapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteCanada
- Study dates
- 20 Aug 2026to Aug 2029
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants must be ≥ 18 years old
- Ability to provide written informed consent
- Actively receiving PD(L)-1 inhibitors
- Progressive disease defined as per RECIST criteria 1.1 on CT metrics as a greater than 20% increase in the sum measurement of lesions, non-target unequivocal progressive disease or a new lesion on CT.
- Radiological progression to ≥ 5 disease sites. Progression at the primary tumor site should be counted within the total number of progressive lesions. For patients with lymph node metastases, each node is counted as one site of metastasis.
- Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
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- Patients with brain metastasis are allowed and should be treated as per standard of care
- All sites of disease can, in the opinion of the investigator, be safely treated and targetable with high-to-intermediate or low dose radiotherapy (taking into account prior local therapy, organ function and underlying medical condition such as inflammatory bowel disease, pulmonary fibrosis, etc.)
- Patients with prior metastases that have been treated with ablative therapies (e.g. radiotherapy, surgery or radiofrequency ablation) before their current line of systemic therapy, are eligible.
- Patients receiving additional systemic therapy agents such as chemotherapy are eligible, provided the other systemic agents are temporarily halted during radiation treatment.
Who cannot join
- Pregnant or breastfeeding individuals are excluded.
- Medical conditions that would hinder the safe administration of radiotherapy or follow-up.
- Patients who are ineligible for immunotherapy.
- Patients with a history of pneumonitis are excluded.
- Presence of an active autoimmune disease.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Canada1 site, 1 recruiting
- Recruiting
Centre Hospitalier de l'Université de Montréal
Montreal, Quebec
Mom Phat, 514-890-8254, mom.phat.chum@ssss.gouv.qc.ca
Houda Bahig, MD PhD
About this study
Official title: Pulse Radiotherapy to Overcome Metastatic Immune System Evasion in Lung Cancer (PROMISE) - Phase I Trial
This phase I study aims to evaluate the safety and effectiveness of adaptive pulsed radiotherapy combined with immunotherapy in patients with metastatic non-small cell lung cancer (NSCLC) resistant to immune checkpoint inhibitors. The primary goal is to assess treatment-related toxicity, while secondary objectives include progression-free survival, overall survival, and quality of life. The study will enroll 32 patients.
Read the detailed description
Background: Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancer cases and is a leading cause of cancer-related death globally. Despite the success of immune checkpoint inhibitors (ICIs) targeting PD-1 and PD-L1, many patients develop resistance to these therapies, either at the start (primary resistance) or over time (secondary resistance). This resistance leads to disease progression during or after treatment, posing a major clinical challenge. Recent studies suggest that combining ICIs with radiotherapy may improve treatment outcomes. Advances in pulsed radiotherapy, including stereotactic radiation cycles, have shown promising results in overcoming ICI resistance in metastatic disease.
Objective: This phase I prospective study aims to evaluate the safety (primary objective) and efficacy of pulsed radiotherapy in combination with PD(L)-1 inhibitors (with or without chemotherapy) in patients with polymetastatic NSCLC who have developed systemic resistance. The hypothesis is that this combination approach could improve patient outcomes by directly reducing tumor burden and enhancing the immune response, while maintaining an acceptable toxicity profile.
Methods: This single-arm phase I study will enroll 32 patients with NSCLC who show disease progression in ≥ 5 extracranial sites while on PD(L)-1 inhibitors (with or without chemotherapy). Pulsed radiotherapy will be delivered in up to 3 cycles, targeting 2 to 5 progressive lesions per cycle. Eligible participants must be 18 years or older, with systemic progression of NSCLC in ≥ 5 sites during treatment with ICIs, and an ECOG performance status of 0-2. Brain metastases are permitted but will not be included in the lesion count.
The primary endpoint is dose-limiting toxicity (DLT), defined by the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0, focusing on grade 3-5 adverse events related to radiotherapy within 180 days of treatment. Secondary endpoints include the development of a clinical workflow for adaptive pulsed radiotherapy, progression-free survival (PFS), overall survival (OS), local recurrence, time to the next systemic treatment, and patient-reported quality of life.
- Conditions
- Non Small Cell Lung Cancer, Metastatic Lung Cancer
- Being tested
- Pulse radiotherapy
- Keywords
- Non small cell lung cancer, Metastatic lung cancer, Progressive disease, Polymetastatic, Immunotherapy resistance, Radiotherapy, Pulse radiotherapy
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Lung Neoplasms, Disease Progression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pulse radiotherapyRadiation
Pulsed radiotherapy combined with PD(L)-1 inhibitors targeting 2 to 5 progressive extracranial lesions per cycle
| Study group | Role | What they receive |
|---|---|---|
| Pulse Radiotherapy | Experimental | Pulsed radiotherapy combined with PD(L)-1 inhibitors targeting 2 to 5 progressive extracranial lesions per cycle Receives: Radiation: Pulse radiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Toxicity
Grade 3-5 toxicity as per Common Terminology Criteria for Adverse Events, version 4.0.
Measured: Within 180 days of radiotherapy completion
Secondary outcomes (4)
Progression-Free Survival (PFS)
Time from the start of adaptive pulse radiotherapy to the first documented disease progression or death from any cause.
Measured: 2 years post radiotherapy
Overall Survival (OS)
Time from the start of treatment to death from any cause.
Measured: 2 years post radiotherapy
Quality of Life (QoL)
Measured using validated patient-reported outcome questionnaires, such as the EORTC QLQ-C30, at baseline, during treatment, and every 6 months.
Measured: until 2 years after radiotherapy
Long term toxicity
Grade 3-5 toxicity, based on the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Measured: More than 180 days post-treatment up to 2 year post treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Oct 2024
- Study start20 Aug 2026
- Primary completionJul 2028 (estimated)
- Study completionAug 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non Small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by Centre hospitalier de l'Université de Montréal (CHUM)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 32 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Varian, a Siemens Healthineers Company
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06622174
- Sponsor's protocol ID
- PROMISE
- Acronym
- PROMISE
- Status last verified
- Jul 2026
- First submitted
- 21 Sep 2024
- Last updated
- 24 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 24 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pulse Radiotherapy to Overcome Metastatic Immune System Evasion in Lung Cancer (PROMISE) - Phase I Trial
- ClinicalTrials.gov ID
- NCT06622174
- Acronym / sponsor ID
- PROMISE / PROMISE
- Conditions
- Non Small Cell Lung Cancer, Metastatic Lung Cancer
- Keywords
- Non small cell lung cancer, Metastatic lung cancer, Progressive disease, Polymetastatic, Immunotherapy resistance, Radiotherapy, Pulse radiotherapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 32 participants (estimated)
- Lead sponsor
- Centre hospitalier de l'Université de Montréal (CHUM)University, hospital or other
- Collaborators
- Varian, a Siemens Healthineers Company
- Study start
- 20 Aug 2026 (actual)
- Primary completion
- Jul 2028 (estimated)
- Study completion
- Aug 2029 (estimated)
- First posted
- 2 Oct 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase I study aims to evaluate the safety and effectiveness of adaptive pulsed radiotherapy combined with immunotherapy in patients with metastatic non-small cell lung cancer (NSCLC) resistant to immune checkpoint inhibitors. The primary goal is to assess treatment-related toxicity, while secondary objectives include progression-free survival, overall survival, and quality of life. The study will enroll 32 patients.
Detailed description
Background: Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancer cases and is a leading cause of cancer-related death globally. Despite the success of immune checkpoint inhibitors (ICIs) targeting PD-1 and PD-L1, many patients develop resistance to these therapies, either at the start (primary resistance) or over time (secondary resistance). This resistance leads to disease progression during or after treatment, posing a major clinical challenge. Recent studies suggest that combining ICIs with radiotherapy may improve treatment outcomes. Advances in pulsed radiotherapy, including stereotactic radiation cycles, have shown promising results in overcoming ICI resistance in metastatic disease.
Objective: This phase I prospective study aims to evaluate the safety (primary objective) and efficacy of pulsed radiotherapy in combination with PD(L)-1 inhibitors (with or without chemotherapy) in patients with polymetastatic NSCLC who have developed systemic resistance. The hypothesis is that this combination approach could improve patient outcomes by directly reducing tumor burden and enhancing the immune response, while maintaining an acceptable toxicity profile.
Methods: This single-arm phase I study will enroll 32 patients with NSCLC who show disease progression in ≥ 5 extracranial sites while on PD(L)-1 inhibitors (with or without chemotherapy). Pulsed radiotherapy will be delivered in up to 3 cycles, targeting 2 to 5 progressive lesions per cycle. Eligible participants must be 18 years or older, with systemic progression of NSCLC in ≥ 5 sites during treatment with ICIs, and an ECOG performance status of 0-2. Brain metastases are permitted but will not be included in the lesion count.
The primary endpoint is dose-limiting toxicity (DLT), defined by the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0, focusing on grade 3-5 adverse events related to radiotherapy within 180 days of treatment. Secondary endpoints include the development of a clinical workflow for adaptive pulsed radiotherapy, progression-free survival (PFS), overall survival (OS), local recurrence, time to the next systemic treatment, and patient-reported quality of life.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pulse Radiotherapy | Experimental | Radiation: Pulse radiotherapyPulsed radiotherapy combined with PD(L)-1 inhibitors targeting 2 to 5 progressive extracranial lesions per cycle |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Participants must be ≥ 18 years old
- Ability to provide written informed consent
- Actively receiving PD(L)-1 inhibitors
- Progressive disease defined as per RECIST criteria 1.1 on CT metrics as a greater than 20% increase in the sum measurement of lesions, non-target unequivocal progressive disease or a new lesion on CT.
- Radiological progression to ≥ 5 disease sites. Progression at the primary tumor site should be counted within the total number of progressive lesions. For patients with lymph node metastases, each node is counted as one site of metastasis.
Key exclusion criteria (5 listed)
- Pregnant or breastfeeding individuals are excluded.
- Medical conditions that would hinder the safe administration of radiotherapy or follow-up.
- Patients who are ineligible for immunotherapy.
- Patients with a history of pneumonitis are excluded.
- Presence of an active autoimmune disease.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pulse radiotherapyPulsed radiotherapy combined with PD(L)-1 inhibitors targeting 2 to 5 progressive extracranial lesions per cycle | Radiation | Pulse Radiotherapy |
Primary outcome
Toxicity
Time frame: Within 180 days of radiotherapy completion
Grade 3-5 toxicity as per Common Terminology Criteria for Adverse Events, version 4.0.
4 secondary outcomes
Progression-Free Survival (PFS)
Time frame: 2 years post radiotherapy
Overall Survival (OS)
Time frame: 2 years post radiotherapy
Quality of Life (QoL)
Time frame: until 2 years after radiotherapy
Long term toxicity
Time frame: More than 180 days post-treatment up to 2 year post treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Aug 2026.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Pulse radiotherapy in people with Non Small Cell Lung Cancer and Metastatic Lung Cancer, run by Centre hospitalier de l'Université de Montréal (CHUM) at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 24 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Houda Bahig, MD PhD (514-890-8254, houda.bahig.med@ssss.gouv.qc.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Toxicity (time frame: Within 180 days of radiotherapy completion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Aug 2026; AzTrials last refreshed its copy on 7 Nov 2026.