Pre-op Radiation Therapy for Mesothelioma

Overseen By John Cho, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University Health Network, Toronto

Disqualifiers: Distant metastasis, Previous thoracic irradiation, Serious non-malignant disease, Previous chemotherapy, Concurrent malignancy, others

Stay on Your Current Meds You can continue your current medications while participating

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether administering a strong dose of radiation to the chest before surgery (pre-op radiation therapy) helps prevent mesothelioma, a cancer linked to asbestos exposure, from spreading beyond the chest. Researchers aim for this approach to stop cancer cells from contaminating other areas during surgery and to reduce the chance of the disease spreading later. The trial targets individuals with newly diagnosed mesothelioma who have good lung function and are prepared for combined treatments like surgery and chemotherapy. As a Phase 1/Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that using radiation therapy before surgery for malignant pleural mesothelioma (MPM) yields promising safety results. One study found that patients generally tolerated the treatment well, although some experienced mostly manageable side effects.

In another study, about 35% of patients faced major complications after surgery, but the death rate remained low at 2.2%. This suggests that while risks exist, they are relatively low. Importantly, radiation therapy before surgery has proven safe when administered carefully.

Overall, evidence suggests that radiation therapy before surgery for MPM is reasonably safe, though side effects can occur. Prospective trial participants should discuss potential risks and benefits with their healthcare provider. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for mesothelioma, like surgery and chemotherapy, focus on removing or reducing tumors after diagnosis. However, pre-operative radiation therapy (Pre-op RT) is unique because it is administered before surgery, aiming to shrink tumors beforehand. Researchers are excited about this treatment because it has the potential to make surgical removal of tumors easier and more effective, possibly improving patient outcomes. Additionally, by targeting cancer cells earlier in the treatment process, Pre-op RT could help prevent the spread of the disease, offering a new approach to managing this challenging condition.

What evidence suggests that pre-op radiation therapy might be an effective treatment for mesothelioma?

Research has shown that radiation therapy (RT) can effectively reduce the chance of mesothelioma tumors returning in the treated area by more than 90%. Past studies demonstrated that using RT before surgery for mesothelioma helped control the disease's local spread. This trial involves a single arm where all participants receive a short, intense course of RT before surgery to target and possibly eliminate cancer cells, potentially preventing their spread during surgery. Combining RT with surgery may lead to better outcomes, as this approach aims to reduce the risk of cancer spreading beyond the chest. Additionally, earlier studies showed that adding chemotherapy after surgery can further improve survival rates. ^{2 4 6 7 8}

Who Is on the Research Team?

John Cho, MD

Principal Investigator

University Health Network, Toronto

Are You a Good Fit for This Trial?

This trial is for adults with a new diagnosis of Malignant Pleural Mesothelioma (MPM) who are in good health otherwise, have not had previous chemotherapy or thoracic radiation, and are not pregnant. They should be able to undergo surgery and have an ECOG performance status of 0-2.

Inclusion Criteria

ECOG performance status of 0-2

Good pulmonary function precluding radiation therapy (FEV>1 L or >40% predicted or DLCO >45% predicted)

Any patient with a new histological diagnosis of malignancy pleural mesothelioma (MPM). Sarcomatoid or biphasic histologies can be included but will be analyzed separately due to their poor prognosis

Exclusion Criteria

Distant metastatic disease

You have received chemotherapy for this or another cancer at the same time.

Women who are currently pregnant or lactating

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Participants receive neoadjuvant hemithoracic intensity modulated radiation therapy (IMRT) for approximately 1 week of 5 daily treatments

1 week

Surgery

Participants undergo extrapleural pneumonectomy 1 week post-radiation therapy

1 week

Chemotherapy

Participants with positive mediastinal lymph nodes receive 3 cycles of chemotherapy, consisting of raltitrexed and cisplatin OR Pemetrexed and cisplatin, 6-12 weeks post-surgery

6-12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment with follow-up visits every 1 to 2 months for the first year, and every 3 months for the second year

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Pre-op RT

Trial Overview The study tests if short intense chest radiation before surgery can prevent the spread of tumor cells during the operation. It's followed by extrapleural pneumonectomy (EPP), which may include additional chemotherapy after surgery.

How Is the Trial Designed?

Group I: All Experimental Treatment 1 Intervention

This is a single arm study. All patients enrolled will be in this arm.

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Published Research Related to This Trial

In a study of 1029 breast cancer patients, starting radiation therapy (RT) within 8 weeks after surgery was linked to improved locoregional recurrence-free survival (LRRFS) for those with luminal subtype breast cancer.

No significant differences in disease-free survival (DFS) or overall survival were found based on the timing of RT initiation, suggesting that while early RT may benefit certain patients, it does not universally affect all outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The impact on clinical outcomes of post-operative radiation therapy delay after neoadjuvant chemotherapy in patients with breast cancer: A multicentric international study. Marta, GN., AlBeesh, R., Pereira, AAL., et al.[2021]

In a study of 60 patients receiving combined immunotherapy and thoracic radiation therapy (iRT), no patients experienced severe grade ≥4 toxicities, indicating a favorable safety profile for this treatment approach.

While some patients did experience grade 3 toxicities, particularly pulmonary and hematologic issues, the overall short-term safety of iRT suggests it can be administered without significant risk of severe adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Combined Immunotherapy and Thoracic Radiation Therapy: Analysis of 3 Single-Institutional Phase I/II Trials. Verma, V., Cushman, TR., Selek, U., et al.[2022]

In a study of 79 patients receiving both immune checkpoint inhibitors and thoracic radiation therapy, the rates of significant adverse events (Grade ≥2) such as pneumonitis, esophagitis, and dermatitis were found to be acceptable and consistent with expectations.

There was no significant difference in the rates of adverse events between patients receiving concurrent (within 1 month) versus sequential (up to 6 months apart) treatments, indicating that concurrent therapy may be a safe option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of combining thoracic radiation therapy with concurrent versus sequential immune checkpoint inhibition. von Reibnitz, D., Chaft, JE., Wu, AJ., et al.[2022]

In a study of 96 lung cancer patients who received thoracic radiotherapy (TRT) after PD-(L)1 inhibitor treatment, nearly 49% developed symptomatic treatment-related pneumonitis, indicating a significant safety concern with this treatment sequence.

Independent risk factors for developing pneumonitis included pulmonary emphysema and lung V20 exposure, highlighting the need for careful patient selection and monitoring when using TRT after PD-(L)1 inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of thoracic radiotherapy after PD-(L)1 inhibitor treatment in patients with lung cancer. Chen, Y., Liu, X., Huang, Z., et al.[2022]

Recent interest in preoperative breast radiation therapy (RT) is growing due to advancements in modern techniques, which may improve its effectiveness compared to older studies that did not change clinical practice.

Current clinical trials are exploring the combination of preoperative RT with novel drugs, aiming to enhance treatment outcomes and optimize translational research in breast cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative breast radiation therapy: Indications and perspectives. Lightowlers, SV., Boersma, LJ., Fourquet, A., et al.[2021]

In a study of 33 patients with resectable non-small-cell lung carcinoma, those who received preoperative radiation therapy followed by surgery (RT + S) had a higher 5-year survival rate of 58% compared to 43% for those who underwent surgery only (SO).

The RT + S group also showed a median survival of 72 months, significantly longer than the 30 months for the SO group, indicating that preoperative radiation therapy may enhance surgical outcomes and overall survival in lung cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of short-course preoperative irradiation in the treatment of resectable bronchus carcinoma: long-term analysis of a randomized pilot-study. Kazem, I., Jongerius, CM., Lacquet, LK., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6656469/

Systemic Therapy Use and Outcomes After Relapse from ... Our findings provide data to highlight the poor outcomes of patients diagnosed with relapsed MPM after preoperative radiation and EPP ± adjuvant chemotherapy, ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7105743/

Surgery for Mesothelioma After Radiation Therapy (SMART) We aimed to assess outcomes and toxicities of treating localized MPM with neoadjuvant radiation therapy (RT) followed by extrapleural pneumonectomy (EPP).

3. withpower.com withpower.com/trial/pre-op-radiation-therapy-for-mesothelioma-3feca

Pre-op Radiation Therapy for Mesothelioma · Info for Participants Radiation therapy (RT) dramatically reduces the risk of tumour recurrence within the irradiated area (\>90%). But patients continue to succumb to MPMs due to ...

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

Perioperative Treatments in Pleural Mesothelioma: State of ... After EPP, the perioperative mortality rate was 3.8%, and morbidity was reported in 50% of cases. Investigating smaller cohorts and various chemotherapy ...

5. asj.amegroups.org asj.amegroups.org/article/view/53775/html

Role of radiation treatment in multimodality treatment of ... A phase II trial of mesothelioma patients undergoing chemotherapy followed by EPP and possibly radiotherapy found that survival increased from 21.9 to 29.1 ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6778401/

A Novel Prospective Study Assessing the Combination of ... Malignant pleural mesothelioma remains difficult to treat, with high failure rates despite optimal therapy. We present a novel prospective trial combining ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1879850020300424

Disease-Related Outcomes and Toxicities of Intensity ... This review explores the use of intensity modulated radiation therapy (IMRT) after lung-sparing surgery in malignant pleural mesothelioma (MPM).

8. 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.