Thoracic CancerPhase 1REPAIRNCT06558175
Reirradiation Dose Escalation in Thoracic Cancers
A Phase 1 study testing stereotactic body radiation therapy (SBRT) in people with Thoracic Cancer and Lung Cancer, run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's.
Trial summary
This is a study involving patients with recurrence, metastasis, or new primary malignancies in the thorax requiring radiation and who have previously received radiotherapy to the thorax, where re-irradiation is expected to exceed the dose constraints used for de novo treatments. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Thoracic Cancer, Lung Cancer, Esophageal Cancer
- What is being tested?
- stereotactic body radiation therapy (SBRT)
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- No sites listed yet
- Study dates
- 30 Oct 2024to 29 Jan 2027
- 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
- Pathologically (histologically or cytologically) proven diagnosis of malignancy, with disease in the thorax requiring re-irradiation for any treatment intent. This may include primary lung cancer of any type, esophageal cancer, recurrences, and/or metastasis from any primary. The intrathoracic disease at the time of enrollment does not itself require a biopsy if a prior biopsy has been obtained at that location or another body site. If the risk of biopsy is unacceptable and there is no prior confirmation of malignancy even at the time of the initial course of radiation, enrollment is permitted provided that the case is discussed at a multidisciplinary tumor board or peer-review rounds.
- Must have received prior photon thoracic radiotherapy ≥ 6 months ago
- Life expectancy > 6 months.
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Age ≥ 18 years
- The current radiation course, when added to the previous radiation doses, exceeds the normal tissue constraints used for de novo treatments for esophagus, heart, lungs, trachea, bronchus, great vessels, or brachial plexus. Forgiveness of the previous dose (i.e. reduction of the previous dose in the cumulative dose calculation) is required to meet constraints. Submission of a pre-plan summary showing the estimated accumulation of current and previously delivered doses is required for registration.
Who cannot join
- Persistent toxicity from previously delivered radiation therapy
- Prior development of symptomatic radiation pneumonitis or immunotherapy-related pneumonitis from previous treatment, even if resolved
- Cumulative radiation dose for all organs-at-risk is already below dose constraints without a recovery factor applied, or with a recovery factor less than the current dose level of the trial. This will be confirmed by the enrolling team after the planning is completed.
- The reirradiation dose-limiting structure is expected to be spinal cord, chest wall, and/or stomach.
- Any prior thoracic radiotherapy < 6 months ago; OR prior thoracic radiotherapy delivered twice daily (compensation for holiday breaks are OK), thoracic radiotherapy delivered by brachytherapy, radionuclides, proton beams, or electron beams.
- Plans for patient to receive daily adaptive radiotherapy in current plan (computed tomography or magnetic resonance based).
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- Plans for the patient to receive other local therapy (including standard fractionated radiotherapy and/or surgery) while on this study, except at disease progression.
- Concurrent systemic therapy (i.e. on the same days as radiation) is not allowed, EXCEPT for patients being treated for intrathoracic lung cancer (NSCLC or SCLC) with curative intent.
- For other patients receiving systemic therapy, they are still eligible for enrollment as long as there is a break in systemic therapy during the course of radiation. For example, if a patient has been on palliative pemetrexed and is planning to continue, they can still be enrolled and would continue to receive pemetrexed; reirradiation would be delivered between cycles, possibly requiring a break in systemic therapy. See Section 6.9 for further details.
- Prior surgical intervention that has significantly changed the position of an organ-at-risk that is expected to be a dose-limiting structure.
- Pregnancy
- The following autoimmune and connective tissue diseases will be excluded: Scleroderma and Systemic lupus erythematosus.
- Patients with interstitial lung disease (ILD).
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: A Safety and Efficacy Trial of Reirradiation Dose Escalation in Thoracic Cancers: Re-evaluating Previous Dose and Allowing Increasing Recovery (REPAIR)
This is a study involving patients with recurrence, metastasis, or new primary malignancies in the thorax requiring radiation and who have previously received radiotherapy to the thorax, where re-irradiation is expected to exceed the dose constraints used for de novo treatments.
Currently, when this group of patients needs another set of radiotherapy, there is a dose limitation based on a percentage of the previous treatment's dose. However, this dose often limits the effectiveness of repeated treatment, with little scientific support for such. Therefore, this study aims to determine the maximally tolerated dose of reirradiation in the thorax, with dose escalation implemented by sequentially increasing the normal tissue recovery factors (i.e. repair factors) to the previously delivered dose.
Using a recovery factor equation associated with a 35% or lower rate of grade 3-5 treatment-related toxicity occurring within 1 year of treatment, accrual will start at level 1 (recovery factor = 10% at 6 months + 0.75% per month thereafter). Patients will be assigned to recovery factors using the TITE-CRM model. The model will use all available information from previously accrued patients to assign the highest dose with a predicted risk of grade 3-5 toxicity of 35% or less.
Read the detailed description
The REPAIR trial aims to identify the magnitude of radiation recovery in the thorax and enable safe reirradiation dose escalation. The trial will provide critical information to support shared-decision making and ensure the risk-benefit trade-offs of reirradiation align with each patient's wishes. In addition, the data from this study will be informative in guiding subsequent studies on the use of reirradiation for other sites (such as the brain, abdomen, and pelvis) and to inform future re-irradiation trials. The objective of this phase I study is to determine the safety of dose escalation via recovery factors applied against previously delivered doses for patients receiving thoracic reirradiation.
This study will use a time-to-event continual reassessment method (TITE-CRM). The study design is based on previous thoracic dose escalation trials.
The primary endpoint of this study is the maximally tolerated dose (MTD) of thoracic reirradiation, implemented by sequentially increasing the normal tissue recovery factors applied to the previously delivered dose. The MTD is the recovery factor equation associated with a ≤ 35% rate of grade 3-5 pre-specified treatment-related toxicity occurring within 1 year of treatment.
- Conditions
- Thoracic Cancer, Lung Cancer, Esophageal Cancer
- Being tested
- stereotactic body radiation therapy (SBRT)
- Keywords
- Re-irradiation, Toxicity, Dose escalation, Oncology
- Medical subject headings
- Lung Neoplasms, Esophageal Neoplasms, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
stereotactic body radiation therapy (SBRT)Radiation
Also called Radiation therapy
Patients will be assigned to treatment doses using the TITE-CRM model.
| Study group | Role | What they receive |
|---|---|---|
| Recovery factor levels | Experimental | Radiation therapy - recovery factor levels Level 1: 6 months (10%) and 0.75%/month Level 2: 6 months (15%) and 0.75%/month Level 3: 6 months (15%) and 1.00%/month Level 4: 6 months (20%) and 1.00%/month Level 5: 6 months (20%) and 1.25%/month Level 6: 6 months (25%) and 1.40%/month Receives: Radiation: stereotactic body radiation therapy (SBRT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximally tolerated dose (MTD)
MTD of radiotherapy for thoracic tumors. The MTD is the dose of radiotherapy associated with a <35% rate of grade 3-5 toxicity occurring within 1 year of treatment.
Measured: occurring within 1 year of treatment
Secondary outcomes (6)
Time to progression
Progression of treated disease
Measured: 1-5 years
Time to distant metastases
Time to distant metastases
Measured: 1-5 years
Progression-Free Survival
Progression-Free Survival
Measured: 1-5 years
Overall survival
Overall survival
Measured: 1-5 years
Patient reported outcome
Functional Assessment of Cancer Therapy: Lung (FACT-L)
Measured: Before treatment and at 3, 6, 9, 12, 18, 24, 36, 48, and 60 months
Quality of Life - EuroQol 5-dimension 5-level
EuroQol 5-dimension 5-level
Measured: Before treatment and at 3, 6, 9, 12, 18, 24, 36, 48, and 60 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Aug 2024
- Study start30 Oct 2024 (estimated)
- Primary completion30 Oct 2026 (estimated)
- Study completion29 Jan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Thoracic CancerStudies of the same condition, open and under way.
- More trials run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph'sThe 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
- Model description
- This multi-institution phase I dose-escalation study for patients undergoing thoracic re-irradiation will use a time-to-event continual reassessment method (TITE-CRM). Accrual will start at level 1 (recovery factor = 10% at 6 months + 0.75% per month thereafter). Patients will be assigned to recovery factors using the TITE-CRM model. The model will use all available information from previously accrued patients to assign the highest dose with a predicted risk of grade 3-5 toxicity of 35% or less.
- Masking
- None (open label)
- Enrolment
- 48 participants (estimated)
Sponsor and investigators
- Lead sponsor
- London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- David Palma, MD,PhD,FRCPC, Principal investigator, London Health Science Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06558175
- Sponsor's protocol ID
- ReDA 14927
- Acronym
- REPAIR
- Status last verified
- Aug 2024
- First submitted
- 14 Aug 2024
- Last updated
- 16 Aug 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Murrell DH, Andratschke N, Bergman AM, Brock K, Dunne EM, Liu M, Karotki A, Louie AV, Warner A, Vickress J, Qu XM, Palma DA. Re-evaluating previous dose and allowing increasing recovery (REPAIR): study protocol for a thoracic reirradiation phase I dose escalation trial. BMC Cancer. 2026 Apr 24;26(1):724. doi: 10.1186/s12885-026-15942-2.
PubMed 42026560
Study at a glance
From the registry record, last updated by the sponsor on 16 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Safety and Efficacy Trial of Reirradiation Dose Escalation in Thoracic Cancers: Re-evaluating Previous Dose and Allowing Increasing Recovery (REPAIR)
- ClinicalTrials.gov ID
- NCT06558175
- Acronym / sponsor ID
- REPAIR / ReDA 14927
- Conditions
- Thoracic Cancer, Lung Cancer, Esophageal Cancer
- Keywords
- Re-irradiation, Toxicity, Dose escalation, Oncology
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 48 participants (estimated)
- Lead sponsor
- London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph'sUniversity, hospital or other
- Study start
- 30 Oct 2024 (estimated)
- Primary completion
- 30 Oct 2026 (estimated)
- Study completion
- 29 Jan 2027 (estimated)
- First posted
- 16 Aug 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 is a study involving patients with recurrence, metastasis, or new primary malignancies in the thorax requiring radiation and who have previously received radiotherapy to the thorax, where re-irradiation is expected to exceed the dose constraints used for de novo treatments.
Currently, when this group of patients needs another set of radiotherapy, there is a dose limitation based on a percentage of the previous treatment's dose. However, this dose often limits the effectiveness of repeated treatment, with little scientific support for such. Therefore, this study aims to determine the maximally tolerated dose of reirradiation in the thorax, with dose escalation implemented by sequentially increasing the normal tissue recovery factors (i.e. repair factors) to the previously delivered dose.
Using a recovery factor equation associated with a 35% or lower rate of grade 3-5 treatment-related toxicity occurring within 1 year of treatment, accrual will start at level 1 (recovery factor = 10% at 6 months + 0.75% per month thereafter). Patients will be assigned to recovery factors using the TITE-CRM model. The model will use all available information from previously accrued patients to assign the highest dose with a predicted risk of grade 3-5 toxicity of 35% or less.
Detailed description
The REPAIR trial aims to identify the magnitude of radiation recovery in the thorax and enable safe reirradiation dose escalation. The trial will provide critical information to support shared-decision making and ensure the risk-benefit trade-offs of reirradiation align with each patient's wishes. In addition, the data from this study will be informative in guiding subsequent studies on the use of reirradiation for other sites (such as the brain, abdomen, and pelvis) and to inform future re-irradiation trials. The objective of this phase I study is to determine the safety of dose escalation via recovery factors applied against previously delivered doses for patients receiving thoracic reirradiation.
This study will use a time-to-event continual reassessment method (TITE-CRM). The study design is based on previous thoracic dose escalation trials.
The primary endpoint of this study is the maximally tolerated dose (MTD) of thoracic reirradiation, implemented by sequentially increasing the normal tissue recovery factors applied to the previously delivered dose. The MTD is the recovery factor equation associated with a ≤ 35% rate of grade 3-5 pre-specified treatment-related toxicity occurring within 1 year of treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This multi-institution phase I dose-escalation study for patients undergoing thoracic re-irradiation will use a time-to-event continual reassessment method (TITE-CRM). Accrual will start at level 1 (recovery factor = 10% at 6 months + 0.75% per month thereafter). Patients will be assigned to recovery factors using the TITE-CRM model. The model will use all available information from previously accrued patients to assign the highest dose with a predicted risk of grade 3-5 toxicity of 35% or less.
| Arm | Type | Receives |
|---|---|---|
| Recovery factor levels | Experimental | Radiation: stereotactic body radiation therapy (SBRT)Radiation therapy - recovery factor levels Level 1: 6 months (10%) and 0.75%/month Level 2: 6 months (15%) and 0.75%/month Level 3: 6 months (15%) and 1.00%/month Level 4: 6 months (20%) and 1.00%/month Level 5: 6 months (20%) and 1.25%/month Level 6: 6 months (25%) and 1.40%/month |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Pathologically (histologically or cytologically) proven diagnosis of malignancy, with disease in the thorax requiring re-irradiation for any treatment intent. This may include primary lung cancer of any type, esophageal cancer, recurrences, and/or metastasis from any primary. The intrathoracic disease at the time of enrollment does not itself require a biopsy if a prior biopsy has been obtained at that location or another body site. If the risk of biopsy is unacceptable and there is no prior confirmation of malignancy even at the time of the initial course of radiation, enrollment is permitted provided that the case is discussed at a multidisciplinary tumor board or peer-review rounds.
- Must have received prior photon thoracic radiotherapy ≥ 6 months ago
- Life expectancy > 6 months.
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Age ≥ 18 years
Key exclusion criteria (13 listed)
- Persistent toxicity from previously delivered radiation therapy
- Prior development of symptomatic radiation pneumonitis or immunotherapy-related pneumonitis from previous treatment, even if resolved
- Cumulative radiation dose for all organs-at-risk is already below dose constraints without a recovery factor applied, or with a recovery factor less than the current dose level of the trial. This will be confirmed by the enrolling team after the planning is completed.
- The reirradiation dose-limiting structure is expected to be spinal cord, chest wall, and/or stomach.
- Any prior thoracic radiotherapy < 6 months ago; OR prior thoracic radiotherapy delivered twice daily (compensation for holiday breaks are OK), thoracic radiotherapy delivered by brachytherapy, radionuclides, proton beams, or electron beams.
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 |
|---|---|---|
| stereotactic body radiation therapy (SBRT)Also: Radiation therapyPatients will be assigned to treatment doses using the TITE-CRM model. | Radiation | Recovery factor levels |
Primary outcome
Maximally tolerated dose (MTD)
Time frame: occurring within 1 year of treatment
MTD of radiotherapy for thoracic tumors. The MTD is the dose of radiotherapy associated with a <35% rate of grade 3-5 toxicity occurring within 1 year of treatment.
6 secondary outcomes
Time to progression
Time frame: 1-5 years
Time to distant metastases
Time frame: 1-5 years
Progression-Free Survival
Time frame: 1-5 years
Overall survival
Time frame: 1-5 years
Patient reported outcome
Time frame: Before treatment and at 3, 6, 9, 12, 18, 24, 36, 48, and 60 months
Quality of Life - EuroQol 5-dimension 5-level
Time frame: Before treatment and at 3, 6, 9, 12, 18, 24, 36, 48, and 60 months
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 16 Aug 2024.
- Derived from this study: PubMed 42026560Murrell DH, Andratschke N, Bergman AM, Brock K, Dunne EM, Liu M, Karotki A, Louie AV, Warner A, Vickress J, Qu XM, Palma DA. Re-evaluating previous dose and allowing increasing recovery (REPAIR): study protocol for a thoracic reirradiation phase I dose escalation trial. BMC Cancer. 2026 Apr 24;26(1):724. doi: 10.1186/s12885-026-15942-2.
- Individual participant dataSharing planned: No
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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.
David Palma, MD,PhD,FRCPC principal investigator
London Health Science Centre
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing stereotactic body radiation therapy (SBRT) in people with Thoracic Cancer and Lung Cancer, run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's.
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 6 inclusion and 13 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: opening soon, as of the sponsor's last update on 16 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
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 Taciano Rocha, PhD, ACRP-CP (5196858500 ext. 56609, taciano.rocha@lhsc.on.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximally tolerated dose (MTD) (time frame: occurring within 1 year of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06558175, which also lists 1 linked publication.
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 16 Aug 2024.