IMPRINT Radiation Therapy for Thymic Cancer

Recruiting at7 trial locations

Overseen by Charles Simone, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Chronic oral steroids

Disqualifiers: Continuous oxygen, Myasthenia gravis, Nephrectomy, others

No Placebo Group

Prior Safety Data

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

The researchers are doing this study to find out whether hemithoracic intensity-modulated pleural radiation therapy (IMPRINT) is a safe treatment that causes few or mild side effects in people with pleural metastases from thymic malignancies. The researchers will also look at whether hemithoracic IMPRINT is effective against participants' cancer.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are on chronic oral steroid therapy for COPD, you may not be eligible to participate.

What data supports the effectiveness of the treatment Intensity-Modulated Pleural Radiation Therapy (IMPRINT) for thymic cancer?

Research shows that intensity-modulated pleural radiation therapy (IMPRINT) has been effective in treating malignant pleural mesothelioma, a type of cancer affecting the lining of the lungs, by improving tumor control and reducing side effects compared to older methods. This suggests that IMPRINT could potentially be effective for thymic cancer as well, given its success in similar conditions. ^{1 2 3 4 5}

Is IMPRINT radiation therapy generally safe for humans?

IMPRINT radiation therapy has been studied for safety in conditions like malignant pleural mesothelioma and thymoma. The studies show that it meets safety standards for organs like the lungs, heart, and esophagus, with low complication probabilities, indicating it is generally safe for humans. ^{1 2 5 6 7}

How is IMPRINT treatment different from other treatments for thymic cancer?

IMPRINT treatment is unique because it uses advanced radiation techniques to target the pleura (the lining of the lungs) while sparing the lung itself, which may reduce damage to nearby organs like the heart and esophagus compared to conventional radiation therapies. ^{2 3 7 8 9}

Research Team

Charles Simone, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for adults aged 18-80 with thymic cancer that has spread to the lung and chest lining but not beyond. Participants must be in good physical condition, have a certain level of lung and kidney function, and cannot be pregnant or breastfeeding. They must agree to use contraception and have no history of severe lung disease, recent heart failure, or specific treatments like thoracic radiation.

Inclusion Criteria

My cancer is confirmed to be thymic malignancy or thymic carcinoma.

My kidney function is good enough for the treatment.

My cancer has spread to the lining of my lungs.

Exclusion Criteria

I am not using any form of birth control.

I was hospitalized for heart failure in the last 30 days.

Pregnant or lactating women

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Participants receive hemithoracic intensity-modulated pleural radiation therapy (IMPRINT) over approximately 6 weeks

6 weeks

28 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including progression-free survival and radiation pneumonitis

12 months

Treatment Details

Interventions

• Intensity-Modulated Pleural Radiation Therapy (IMPRINT) (Radiation)

Trial Overview The study is testing Intensity-Modulated Pleural Radiation Therapy (IMPRINT) specifically for patients with pleural metastases from thymic malignancies. It aims to determine the safety profile of IMPRINT and its effectiveness in controlling cancer spread within the chest area.

Participant Groups

Group I: Hemithoracic Intensity-Modulated Pleural Radiation Therapy (IMPRINT) Experimental Treatment 1 Intervention

Radiation will be administered over approximately 6 weeks to 50.4 Gy in 28 fractions with an optional SIB to gross residual disease.

Intensity-Modulated Pleural Radiation Therapy (IMPRINT) is already approved in Japan for the following indications:

Approved in Japan as IMPRINT for:

• Thymic carcinoma with pleural metastases

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Lisa M. DeAngelis

Memorial Sloan Kettering Cancer Center

Chief Medical Officer since 2021

MD from Columbia University

Selwyn M. Vickers

Memorial Sloan Kettering Cancer Center

Chief Executive Officer since 2022

MD from Johns Hopkins University

Findings from Research

Intensity modulated radiation therapy (IMRT) showed a high objective response rate of 97% in 31 patients with pleural recurrence of thymoma, indicating its efficacy as a treatment option when surgery is not possible.

Higher radiation doses (up to 50 Gy) were associated with longer local control times, but out-of-field recurrences were common, suggesting careful monitoring and management of potential new recurrences due to risks like radiation-induced pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity Modulated Radiation Therapy for Pleural Recurrence of Thymoma: A Prospective Phase 2 Study. Wang, CL., Gao, LT., Lyu, CX., et al.[2021]

In a phase II study involving 45 patients with malignant pleural mesothelioma, hemithoracic intensity-modulated pleural radiation therapy (IMPRINT) was found to be safe, with only 2 patients experiencing grade 3 radiation pneumonitis, and no severe (grade 4 or 5) toxicities reported.

The study demonstrated promising outcomes, with a median overall survival of 23.7 months and a 2-year overall survival rate of 59% for patients with resectable tumors, suggesting that IMPRINT can be effectively integrated into a lung-sparing treatment approach following chemotherapy and pleurectomy-decortication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Study of Hemithoracic Intensity-Modulated Pleural Radiation Therapy (IMPRINT) As Part of Lung-Sparing Multimodality Therapy in Patients With Malignant Pleural Mesothelioma. Rimner, A., Zauderer, MG., Gomez, DR., et al.[2022]

In a study of 209 patients with malignant pleural mesothelioma, those receiving adjuvant hemithoracic intensity-modulated pleural radiotherapy (IMPRINT) had a significantly improved overall survival (OS) of 20.2 months compared to 12.3 months for those receiving conventional radiotherapy (CONV).

Patients treated with IMPRINT experienced lower rates of grade 2 or higher esophagitis (23%) compared to those treated with CONV (47%), indicating that IMPRINT may offer a safer treatment option with reduced toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved Outcomes with Modern Lung-Sparing Trimodality Therapy in Patients with Malignant Pleural Mesothelioma. Shaikh, F., Zauderer, MG., von Reibnitz, D., et al.[2021]

In a study of 58 patients with malignant pleural mesothelioma treated with intensity-modulated pleural radiation therapy (IMPRINT), 36% experienced local pleural recurrence, with a 1-year cumulative incidence rate of 27%.

CT scans revealed that new or increased multiple pleural nodules were the most common indicator of local recurrence, and any pattern of increased nodular pleural thickening should raise suspicion for recurrence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Computed tomography features of local pleural recurrence in patients with malignant pleural mesothelioma treated with intensity-modulated pleural radiation therapy. Halpenny, D., Raj, M., Rimner, A., et al.[2021]

Daily exposure to low-dose radiation (100 mGy) over 10 weeks caused significant DNA damage in lung tissue, with varying levels of damage observed in different cell types, indicating that some lung cells are more sensitive to radiation than others.

The extent of DNA damage was influenced by the genetic background related to DNA repair capabilities, suggesting that individuals with different genetic profiles may experience varying risks of lung toxicity and potential secondary malignancies from low-dose radiation exposure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Even low doses of radiation lead to DNA damage accumulation in lung tissue according to the genetically-defined DNA repair capacity. Flockerzi, E., Schanz, S., Rübe, CE.[2018]

In a study involving eleven patients with thymoma, advanced radiotherapy techniques like 5-field and 7-field IMRT, as well as VMAT, showed better target coverage and reduced normal tissue complication probabilities (NTCP) for organs-at-risk compared to traditional 3D conformal radiotherapy (3D-CRT).

The 7F-IMRT technique significantly lowered the risk of lung complications, such as pneumonitis, compared to FA-VMAT, while 5F-IMRT also outperformed PA-VMAT in protecting lung tissue, indicating that these advanced techniques can enhance safety in radiotherapy for thymoma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NTCP Calculations of Five Different Irradiation Techniques for the Treatment of Thymoma. Mazonakis, M., Kachris, S., Tolia, M., et al.[2023]

Postoperative mediastinal radiotherapy (MRT) for invasive thymoma showed a 5-year overall survival rate of 79% and a low incidence of significant side effects, with only 5.8% of patients experiencing grade 2 or higher radiation pneumonitis.

Low-dose entire hemithorax radiotherapy (EHRT) for pleural dissemination demonstrated a 71% control rate for pleural dissemination in stage IVa patients, suggesting it is a safe and effective addition to treatment for controlling this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Invasive thymoma: postoperative mediastinal irradiation, and low-dose entire hemithorax irradiation in patients with pleural dissemination. Sugie, C., Shibamoto, Y., Ikeya-Hashizume, C., et al.[2016]

Proton therapy (PT) significantly reduced radiation doses to critical organs such as the heart, lungs, and esophagus by an average of 36.5%, 33.5%, and 60% respectively, compared to intensity-modulated radiotherapy (IMRT), which may lead to lower toxicity levels.

In a study of six patients with thymic malignancies, no patients experienced severe (grade ≥3) toxicities after receiving PT, indicating a favorable safety profile while maintaining similar survival outcomes compared to historical data.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rationale and early outcomes for the management of thymoma with proton therapy. Zhu, HJ., Hoppe, BS., Flampouri, S., et al.[2022]

A patient with recurrent thymoma in the left pleural cavity showed significant tumor regression after receiving a high-dose radiotherapy treatment of 6,600 cGy, despite previous chemotherapy failure.

One year post-treatment, the patient's pulmonary function remained stable, and cardiac function was normal two years later, suggesting that high-dose hemithorax irradiation can be safely considered in select cases without significant toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-dose hemithorax irradiation in a patient with recurrent thymoma: a study of pulmonary and cardiac radiation tolerance. Bogart, JA., Sagerman, RH.[2019]

References

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

Intensity Modulated Radiation Therapy for Pleural Recurrence of Thymoma: A Prospective Phase 2 Study. [2021]

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

Phase II Study of Hemithoracic Intensity-Modulated Pleural Radiation Therapy (IMPRINT) As Part of Lung-Sparing Multimodality Therapy in Patients With Malignant Pleural Mesothelioma. [2022]

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

Improved Outcomes with Modern Lung-Sparing Trimodality Therapy in Patients with Malignant Pleural Mesothelioma. [2021]

4. Germany pubmed.ncbi.nlm.nih.gov

Computed tomography features of local pleural recurrence in patients with malignant pleural mesothelioma treated with intensity-modulated pleural radiation therapy. [2021]

5. Ireland pubmed.ncbi.nlm.nih.gov

Even low doses of radiation lead to DNA damage accumulation in lung tissue according to the genetically-defined DNA repair capacity. [2018]

6. Switzerland pubmed.ncbi.nlm.nih.gov

NTCP Calculations of Five Different Irradiation Techniques for the Treatment of Thymoma. [2023]

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

Invasive thymoma: postoperative mediastinal irradiation, and low-dose entire hemithorax irradiation in patients with pleural dissemination. [2016]

8. China pubmed.ncbi.nlm.nih.gov

Rationale and early outcomes for the management of thymoma with proton therapy. [2022]

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

High-dose hemithorax irradiation in a patient with recurrent thymoma: a study of pulmonary and cardiac radiation tolerance. [2019]