Reirradiation Dose Escalation in Thoracic Cancers

NCT06558175 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: ReDA 14927
• Study Type: interventional
• Target: 48
• Locations: 0 countries
• Sites: N/A

Brief 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. 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.

Conditions

Thoracic Cancer; Lung Cancer; Esophageal Cancer

Keywords

Re-irradiation; Toxicity; Dose escalation; Oncology

Outcome Measures

Primary Outcomes (1)

• 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.

  occurring within 1 year of treatment

Secondary Outcomes (6)

• Time to progression

  1-5 years

• Time to distant metastases

  1-5 years

• Progression-Free Survival

  1-5 years

• Overall survival

  1-5 years

• Patient reported outcome

  Before treatment and at 3, 6, 9, 12, 18, 24, 36, 48, and 60 months

Study Arms (1)

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

Radiation: stereotactic body radiation therapy (SBRT)

Interventions

stereotactic body radiation therapy (SBRT) RADIATION

Patients will be assigned to treatment doses using the TITE-CRM model.

Also known as: Radiation therapy

Recovery factor levels

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).
• 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).

Sponsors & Collaborators

• London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's: lead

MeSH Terms

Conditions

Lung Neoplasms; Esophageal Neoplasms; Neoplasms

Interventions

Radiosurgery; Radiotherapy

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• David Palma, MD,PhD,FRCPC

  London Health Science Centre

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Taciano Rocha, PhD, ACRP-CP

CONTACT

5196858500; taciano.rocha@lhsc.on.ca

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: August 14, 2024
• First Posted: August 16, 2024
• Study Start: October 30, 2024
• Primary Completion (Estimated): October 30, 2026
• Study Completion (Estimated): January 29, 2027
• Last Updated: August 16, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share