Pre-Transplant Radiation for Lung Cancer

(NORTh STAR Trial)

Overseen By Marc de Perrot, MD, MSc

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Marc de Perrot

Disqualifiers: Mediastinal nodes metastasis, distant metastasis, others

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

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new radiation treatment to determine if it can benefit patients with serious lung diseases and early-stage lung cancer before a lung transplant. The treatment aims to use radiation to enhance the body's immune response against cancer, potentially reducing the risk of cancer recurrence after the transplant. Suitable candidates for this trial include those with severe lung disease and small lung tumors that cannot be treated with surgery or intense radiation. As an unphased trial, this study provides a unique opportunity to contribute to groundbreaking research that could improve future treatment options.

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 prior data suggests that this radiation therapy is safe for lung cancer patients?

Research has shown that radiation therapy, like the one used in this study, is generally well-tolerated. Studies have found that repeated courses of radiation treatment often yield good results with manageable safety concerns, meaning most patients do not experience severe side effects.

In lung cancer, stereotactic body radiation therapy (SBRT) has been used safely and effectively to treat lung tumors. This focused radiation targets the cancer while minimizing harm to healthy tissue. Although side effects can occur, evidence suggests that the benefits often outweigh the risks for many patients.

In this trial, patients will receive different doses based on their condition, starting with lower doses to determine the safest amount. This careful approach helps ensure the treatment remains as safe as possible for all participants. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using pre-transplant radiation for lung cancer because it offers a novel approach to managing patients with end-stage lung disease and suspected early-stage lung cancer. Unlike traditional treatments that often involve surgery or chemotherapy, this method uses targeted radiation doses to potentially shrink tumors before a lung transplant. This could make surgery safer and more effective by reducing tumor size and minimizing the risk of cancer spread. The ability to tailor radiation doses based on tumor size and patient condition offers a personalized treatment strategy, which is a promising step forward in improving outcomes for these patients.

What evidence suggests that this radiation treatment might be an effective treatment for lung cancer?

Research has shown that radiation therapy can help treat lung cancer. In this trial, participants will receive radiation therapy, with doses tailored to specific patient groups. For example, one study found that 21% of lung cancer patients who received stereotactic radiosurgery were still alive after five years. Additionally, combining surgery with radiation therapy has improved survival rates, suggesting that using different treatments together can be beneficial. Stereotactic Body Radiation Therapy (SBRT), a precise form of radiation, works well for treating central and multiple lung tumors. This evidence suggests that radiation therapy, especially when combined with other treatments, can be a promising option for lung cancer. ^{1 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with end-stage lung disease and suspected early-stage lung cancer, who are eligible for a lung transplant but can't have curative surgery. It's not for those with previous chest radiation, mediastinal node or distant metastasis, or other conditions that could affect participation.

Inclusion Criteria

Subjects must be able to understand the potential risks and benefits of the study and must be able to read and provide written, informed consent for the study.

My lung cancer is in early stage but can't be treated with surgery or targeted radiation.

I had surgery to remove a lung tumor and have no other cancer spread that can be treated.

Exclusion Criteria

You have a medical condition that may affect your ability to follow the treatment as required, according to the team's evaluation.

I am under 18 years old.

My cancer has spread to the lymph nodes in my chest, confirmed by a specific biopsy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Non-ablative oligofractionated radiation therapy (NORT) is administered to determine the maximum tolerated dose (MTD) before lung transplantation.

3-6 weeks

Multiple visits for radiation sessions

Surgical Transplantation

Resection of the radiated tumor at the time of lung transplantation.

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of maximum tolerated dose and patient morbidity.

Up to four years

What Are the Treatments Tested in This Trial?

Interventions

• Radiation

Trial Overview The study tests non-ablative oligofractionated radiation therapy (NORT) before lung transplantation to see if it's safe and can act as a 'radiovaccination', potentially reducing cancer recurrence by triggering an immune response against the tumor.

How Is the Trial Designed?

Group I: Experimental: Radiation Experimental Treatment 1 Intervention

Patients will be differentiated into 4 groups: 1. Patients with end-stage interstitial lung disease (ILD) and suspected stage I (up to 4 cm) primary lung cancer 2. Patients with end-stage lung disease other than ILD (e.g. emphysema/COPD, cystic fibrosis and pulmonary hypertension) and suspected stage I (up to 4 cm) primary lung cancer 3. Patients with multifocal primary lung cancer (e.g. multifocal adenocarcinoma) in the absence of nodal metastasis and distant metastasis. 4. Patients with isolated pulmonary metastasis in the absence of other sites of malignancy (primary and metastatic). For this study, different doses will be used for each different group depending on their tumour size. The first 3 patients will start with a dose of 4 Gy, for the ILD group, or 8 Gy, for the non ILD group. The doses are then increased incrementally until the dose limiting toxicity is reached.

Radiation is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Radiation Therapy for:

• Cancer treatment
• HPV-positive throat cancer
• Various types of tumors

Approved in United States as Radiation Therapy for:

• Cancer treatment
• HPV-positive throat cancer
• Various types of tumors

Approved in Canada as Radiation Therapy for:

• Cancer treatment
• HPV-positive throat cancer
• Various types of tumors

Approved in Japan as Radiation Therapy for:

• Cancer treatment
• HPV-positive throat cancer
• Various types of tumors

Approved in China as Radiation Therapy for:

• Cancer treatment
• HPV-positive throat cancer
• Various types of tumors

Approved in Switzerland as Radiation Therapy for:

• Cancer treatment
• HPV-positive throat cancer
• Various types of tumors

Who Is Running the Clinical Trial?

Marc de Perrot

Lead Sponsor

Trials

2

Recruited

40+

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Published Research Related to This Trial

In a study of 378 lung carcinoma patients treated with combined radiotherapy and surgery, preoperative radiotherapy did not complicate surgery significantly, although there was a slight increase in postoperative complications, primarily pyoinflammatory issues.

Patients who showed complete regression of their tumors after preoperative radiotherapy had a remarkable 63.2% 5-year survival rate post-surgery, highlighting the potential effectiveness of this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Surgical treatment of lung cancer in patients with preoperative radiation therapy]. Dobrovolśkiĭ, SR., Grigoréva, SP., Ivanov, AN., et al.[2006]

Radiation therapy is a common treatment for locally advanced non-small cell lung cancer, but only 5% of patients survive for 5 years, highlighting the need for improved treatment strategies.

Advancements in radiobiology and technology, such as 3D planning using CT and MRI, have enhanced local control and survival, and combining radiation with chemotherapy may offer further benefits, although the optimal sequence of these treatments remains unclear.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Curative radiotherapy in locally advanced non-small-cell bronchial carcinoma (NSCLC)]. von Briel, C., Betticher, DC., Ris, HB.[2008]

In a study of 43 lung cancer patients treated with planned preoperative radiotherapy from 1961 to 1966, a five-year survival rate of 23% was achieved, indicating a potential benefit of this treatment approach.

The paper discusses specific clinical situations where preoperative radiotherapy may offer advantages over alternative treatment methods, suggesting its strategic use in lung cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative irradiation for carcinoma of the bronchus. Monk, I., Woods, W.[2019]

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]

The combination of PD-1/PD-L1 blockade with thoracic radiotherapy is now the standard treatment for locally advanced non-small-cell lung cancer, but safety data is primarily from retrospective studies and small clinical trials.

There is a need for longer and more rigorous follow-up studies to better understand the pulmonary safety and potential toxicity of this combined therapy in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rethinking pulmonary toxicity in advanced non-small cell lung cancer in the era of combining anti-PD-1/PD-L1 therapy with thoracic radiotherapy. Li, M., Gan, L., Song, A., et al.[2019]

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]

Radiation therapy (RT) has become a crucial treatment option for patients with advanced non-small cell lung cancer (NSCLC), especially for those who cannot undergo surgery.

Innovative RT schedules and combined chemotherapy regimens are key to enhancing treatment outcomes for locally advanced NSCLC, with potential improvements in patient selection strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of radiotherapy in non-small cell lung cancer. Sause, WT.[2019]

In a study of 26 lung cancer patients treated with preoperative radiotherapy, the surgical resection rate was very high at 92.3%, with no operative mortality or complications leading to death.

Preoperative radiation improved the 1-year survival rate by 3.9% and the 3-year survival rate by 17.5% compared to surgery alone, indicating its potential benefits in enhancing surgical outcomes and preventing cancer spread.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Preoperative radiotherapy and ultrastructural pathology of lung cancer]. Li, YT.[2006]

Radiation therapy (RT) is a key treatment for lung cancer, aiming to effectively target tumors while minimizing side effects, influenced by factors like tumor type and location.

Recent advancements in RT techniques, such as intensity-modulated radiation therapy and stereotactic body radiation therapy, have improved treatment efficacy and significantly reduced toxicity for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Radiotherapy: Basic Concepts And Recent Techniques Advances For Thoracic Malignancies. Amorim, M., Costa, PS., Costa, MA.[2023]

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]

In a study of 1361 patients undergoing radiation therapy for locally advanced lung cancer, over half (53%) reported significant declines in their quality of life (QoL) by the end of treatment, indicating that treatment can have a substantial impact on patient well-being.

While clinician-reported adverse events (AEs) were linked to declines in QoL, the correlation was only moderate, suggesting that patient-reported outcomes (PROs) are crucial for understanding the full impact of treatment and may help identify when interventions are needed to improve patient experiences.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association Between Physician- and Patient-Reported Symptoms in Patients Treated With Definitive Radiation Therapy for Locally Advanced Lung Cancer in a Statewide Consortium. Wilkie, JR., Hochstedler, KA., Schipper, MJ., et al.[2022]

Curative resection is only beneficial for patients with localized lung cancer, while curative radiotherapy is recommended for those who cannot undergo surgery due to medical reasons.

Radiotherapy can provide palliative relief for 50 to 75 percent of patients with symptoms from lung cancer, and chemotherapy shows significant effectiveness in small cell carcinoma, leading to tumor regression and improved survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lung cancer. Rodescu, D.[2019]

Radiation therapy is a key treatment for lung cancer, used in various situations including small cell lung cancer and non-small cell lung cancer, often alongside chemotherapy and surgery.

Palliative radiation therapy effectively alleviates severe symptoms caused by lung tumors and metastases, improving the quality of life for patients with advanced disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Radiotherapy in malignant lung tumors]. Thöni, AF.[2008]

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