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

100 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the treatment Pre-op RT for mesothelioma?

Research on similar treatments, like preoperative radiation therapy for lung and esophageal cancers, shows that it can improve survival rates and increase the chances of successful surgery. For instance, in lung cancer, patients who received pre-op radiation had a higher survival rate and more successful tumor removal compared to those who had surgery alone. ^{1 2 3 4 5}

Is pre-op radiation therapy generally safe for humans?

Pre-op radiation therapy has been studied in patients with endometrial carcinoma, where it showed similar rates of mild and serious complications compared to post-op radiation therapy. The most common complications involved the rectum, small bowel, femur, or lower extremity, and the use of external radiation therapy was a significant predictor of complications. ^{6 7 8 9 10}

How is the treatment Pre-op RT for Mesothelioma different from other treatments?

Pre-op RT (preoperative radiation therapy) for Mesothelioma is unique because it involves delivering radiation before surgery to potentially shrink the tumor and improve surgical outcomes. This approach is different from traditional treatments that may use radiation after surgery or not at all, and it aims to reduce the risk of cancer returning in the same area. ^{11 12 13 14 15}

What is the purpose of this trial?

Malignant pleural mesotheliomas (MPMs) are tumours associated with asbestos exposure involving the tissue lining surrounding the lung. Radiation therapy (RT) dramatically reduces the risk of tumour recurrence within the irradiated area (\>90%). But patients continue to succumb to MPMs due to the tumour spreading outside the chest cavity. This may be due to tumour cells inadvertently contaminating areas outside the chest cavity during surgery. The study will look at whether giving a short intense course of chest radiation just prior to surgery will sterilized these tumour cells and thus, avoid or reduce contamination of the areas outside the chest cavity. The investigators hypothesize that short neoadjuvant (pre-operative) hemithoracic RT, followed by immediate planned extrapleural pneumonectomy (EPP) (+/- adjuvant chemotherapy) will reduce the risk of intra-operative seeding and reduce the incidence of distant metastatic disease.

Research Team

John Cho, MD

Principal Investigator

University Health Network, Toronto

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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 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]

References

1. United States 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. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

The role of radiation therapy in treating patients with potentially resectable carcinoma of the esophagus. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Neoadjuvant radiochemotherapy for locally advanced gastric cancer: long-term results of a phase I trial. [2013]

4. England pubmed.ncbi.nlm.nih.gov

Preoperative breast radiation therapy: Indications and perspectives. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Cancer of the distal esophagus and cardia: preoperative irradiation prolongs survival. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Analysis of complications in patients with endometrial carcinoma receiving adjuvant irradiation. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Safety of thoracic radiotherapy after PD-(L)1 inhibitor treatment in patients with lung cancer. [2022]

8. France pubmed.ncbi.nlm.nih.gov

[Dosimetric factors related to postoperative pulmonary complications in locally advanced esophageal cancers treated with preoperative chemoradiotherapy: Literature review]. [2020]

9. United States pubmed.ncbi.nlm.nih.gov

Safety of Combined Immunotherapy and Thoracic Radiation Therapy: Analysis of 3 Single-Institutional Phase I/II Trials. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Safety of combining thoracic radiation therapy with concurrent versus sequential immune checkpoint inhibition. [2022]

11. Netherlands 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. [2021]

12. United States pubmed.ncbi.nlm.nih.gov

The Interval Between Preoperative Radiation and Surgery Is Not Associated with Overall Survival for Soft-tissue Sarcomas: An Analysis of the National Cancer Database. [2023]

13. United States pubmed.ncbi.nlm.nih.gov

Intensity modulated radiation-therapy for preoperative posterior abdominal wall irradiation of retroperitoneal liposarcomas. [2019]

14. Switzerland pubmed.ncbi.nlm.nih.gov

Effect of pre-operative radiation therapy on surgical outcome in retroperitoneal sarcoma. [2023]

15. Australia pubmed.ncbi.nlm.nih.gov

Outcomes of preoperative radiotherapy and resection of retroperitoneal sarcoma. [2019]