Pre-Surgery Radiation Therapy for Mesothelioma

(SMARTER Trial)

Overseen By John Cho, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University Health Network, Toronto

Disqualifiers: Metastatic disease, Poor performance, Others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 4

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the safest dose of a new radiation treatment for individuals with malignant pleural mesothelioma, a type of lung cancer often linked to asbestos exposure. The trial uses experimental boost radiation (Background and Boost RT) to target the cancer more intensely before surgery. The goal is to assess whether this approach can better control the disease. Individuals recently diagnosed with mesothelioma and in good health, aside from their cancer, might be suitable candidates for this trial. As an unphased trial, this study provides a unique opportunity to contribute to groundbreaking research that could enhance future treatment options.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that this radiation therapy is safe for mesothelioma patients?

Previous studies have shown that stereotactic body radiation therapy, a precise type of radiation treatment, is safe for treating pleural mesothelioma, with a low risk of serious side effects. Research indicates that this radiation can effectively control the disease in the treated area. However, exposure to ionizing radiation has been linked to a higher risk of developing mesothelioma.

In this trial, the researchers are testing a treatment that uses both background and boost radiation to find the safest dose. They will start with low doses and gradually increase them to determine the highest dose patients can tolerate without serious issues. This careful approach helps ensure participant safety. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about pre-surgery radiation therapy for mesothelioma because it introduces a novel approach by combining a "Background" and "Boost" radiation dose targeted to the tumor before surgery. Unlike the standard treatments that typically involve surgery followed by post-operative radiation or chemotherapy, this method aims to shrink the tumor beforehand, potentially making surgery more effective. Additionally, the radiation is delivered over a short period of 5-7 days, which might lead to quicker results. This approach has the potential to improve surgical outcomes and reduce the chances of cancer returning, making it a promising option for mesothelioma patients.

What evidence suggests that this radiation therapy is effective for mesothelioma?

Research has shown that radiation therapy (RT) can help manage symptoms for patients with malignant pleural mesothelioma. In some studies, patients receiving RT lived without disease progression for an average of 18 months, though there was a risk of side effects. In this trial, participants will receive an experimental boost radiation targeting large tumor areas with uneven high doses, potentially triggering an immune response to help control the disease. While this approach appears promising, researchers continue to determine the safest and most effective dose. ^{2 3 5 6 7}

Who Is on the Research Team?

John Cho, MD

Principal Investigator

Princess Margaret Hospital, Canada

Are You a Good Fit for This Trial?

Adults over 18 with early-stage malignant pleural mesothelioma, good lung function, and performance status. They must be new diagnoses without prior thoracic radiation or chemotherapy for this cancer or others within the last 3 years (except certain non-invasive cancers). Pregnant women are excluded.

Inclusion Criteria

My lung function is good enough that I can't have radiation therapy.

I can take care of myself and am up and about more than half of my waking hours.

I am eligible for treatment that combines different methods.

Exclusion Criteria

I have had radiation therapy to the chest area before.

I have had cancer before, but it was either non-melanoma skin cancer, non-invasive breast cancer, prostate cancer treated to cure, or any cancer treated over 3 years ago without recurrence.

I need help with my daily activities or am unable to do them.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Participants receive background and boost radiation therapy to determine the maximum tolerated dose

5-7 days

3 visits (in-person)

Surgery

Surgery is performed approximately 1-2 weeks after completing radiation therapy

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety, effectiveness, and quality of life after treatment

Up to five years

What Are the Treatments Tested in This Trial?

Interventions

• Background and Boost RT
• Surgery for Mesothelioma

Trial Overview The study is testing how much radiation can be safely given to mesothelioma patients before surgery. It involves increasing doses of background plus boost radiation until reaching a maximum safe level or a set dose limit.

How Is the Trial Designed?

Group I: Radiation Experimental Treatment 1 Intervention

This study involves a 3+3 design. The starting cohort (n=3) will receive a neoadjuvant Background dose to the affected hemithorax (starting at 0 cGy) as well as concomitant Boost dose (of at least 2100 cGy) to a part of the gross tumour volume (GTV). The radiation will be delivered over 3 alternate days over 5-7 calendar days followed by macroscopically complete extensive pleural resection (either extra-pleural pneumonectomy or extended pleurectomy decortication, at the surgeon's discretion) after 7 to 14 days. If no dose limiting toxicities (DLTs) seen, then the Background RT dose will be increased by 600 cGy (up to 1800 cGy) and the cohort (n=3) for the next dose level will be accrued. If only 1 DLT seen, then an additional 3 patients will be treated on this dose level. If 2 or more DLTs seen at any given dose level, then the previous dose level will be defined as the maximum tolerated dose (MTD). Patients will be stratified by type of resection.

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Citations

1. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0167814023093647

Clinical outcomes of stereotactic body radiation therapy for ... The objective of this study is to determine the outcomes and toxicities of patients with malignant pleural mesothelioma (MPM) treated with stereotactic body ...

2. mdpi.com mdpi.com/2072-6694/17/19/3199

Perioperative Treatments in Pleural Mesothelioma: State of ... This approach resulted in a median disease-free survival of 18.0 months and a 5-year local relapse rate of 20.1%, though it revealed a high toxicity rate, with ...

3. apm.amegroups.org apm.amegroups.org/article/view/49429/html

Initial clinical experience treating patients with palliative ... Background: Radiation therapy (RT) can provide effective symptomatic palliation in patients with malignant pleural mesothelioma (MPM). Advances in RT ...

4. thegreenjournal.com thegreenjournal.com/article/S0167-8140(24)00058-6/fulltext

Stereotactic body radiation therapy for pleural mesothelioma Comment to “Clinical outcomes of stereotactic body radiation therapy for malignant pleural mesothelioma” by Shin et al. Giovanni L. Ceresoli

5. jto.org jto.org/article/S1556-0864(19)30380-6/fulltext

The Use of Radiation Therapy for the Treatment ... Factors influencing the outcome of radiotherapy in malignant mesothelioma of the pleura--a single-institution experience with 189 patients.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10923065/

Clinical outcomes of stereotactic body radiation therapy for ... Prognosis is poor, and the 5-year relative survival rate is 12%. Treatment options for those with resectable disease usually incorporate ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8817084/

Relationship between exposure to ionizing radiation and ... Our analysis supports the hypothesis that exposure to ionizing radiation can lead to a significant increased risk of developing mesothelioma.