IMPRINT Radiation Therapy for Thymic Cancer

Recruiting at 7 trial locations

Overseen By Andreas Rimner, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Chronic oral steroids

Disqualifiers: Continuous oxygen, Myasthenia gravis, Nephrectomy, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 28

36 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new radiation therapy called hemithoracic intensity-modulated pleural radiation therapy (IMPRINT) to assess its safety and effectiveness for individuals with thymic cancer that has spread to the lung lining (pleural metastases). The goal is to determine whether this treatment causes few or mild side effects and effectively combats the cancer. Individuals with confirmed thymic cancer with pleural metastases and no cancer spread outside the chest may be suitable candidates for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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 prior data suggests that hemithoracic intensity-modulated pleural radiation therapy (IMPRINT) is safe for people with pleural metastases from thymic malignancies?

Research has shown that hemithoracic intensity-modulated pleural radiation therapy (IMPRINT) is generally safe for patients. In studies on malignant pleural mesothelioma, patients tolerated this treatment well, with most experiencing only mild side effects. The rate of radiation pneumonitis (RP), an inflammation of the lungs due to radiation, was manageable. This indicates that the treatment typically does not cause serious problems. However, each person's experience may vary. It is important to discuss potential risks with a healthcare provider before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Intensity-Modulated Pleural Radiation Therapy (IMPRINT) for thymic cancer because it offers a more targeted approach compared to traditional radiation therapy. Unlike conventional methods, which may expose healthy tissues to high doses, IMPRINT precisely directs radiation to affected areas, potentially minimizing damage to surrounding organs. This precision could lead to fewer side effects and improved quality of life for patients, making it a promising option in the fight against thymic cancer.

What evidence suggests that hemithoracic IMPRINT is effective for thymic cancer?

Research has shown that hemithoracic intensity-modulated pleural radiation therapy (IMPRINT), which participants in this trial will receive, may help treat cancer that has spread to the lung lining from thymic cancer. After surgery, radiation therapy like IMPRINT can help control tumors for longer periods. Past studies indicate that the chance of the cancer not worsening for five years after surgery is about 29-45%. Another study found that similar radiation methods could increase this chance to 60-70% over two years. These findings suggest that IMPRINT might effectively prevent thymic cancer from worsening. ^{1 2 4 6 7}

Who Is on the Research Team?

Charles Simone, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Intensity-Modulated Pleural Radiation Therapy (IMPRINT)

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.

How Is the Trial Designed?

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 United States, European Union, Japan for the following indications:

Approved in United States as IMPRINT for:

• Thymic cancer with pleural metastases

Approved in European Union as IMPRINT for:

• Thymic malignancies with pleural dissemination

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+

Published Research Related to This Trial

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]

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]

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 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]

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]

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 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]

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]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.TPS8616

Phase II study of hemithoracic intensity-modulated pleural ... After surgical resection of pleural metastases, the 5-year progression-free survival (PFS) rate is about 29-45%. While radiation therapy (RT) is ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05354570

A Study of Intensity-Modulated Pleural Radiation Therapy ... The researchers are doing this study to find out whether hemithoracic intensity-modulated pleural radiation therapy (IMPRINT) is a safe treatment that causes ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9385872/

Radiation strategy and techniques for metastatic pleural ... After surgical resection of pleural metastasis, progression can occur with a 2-year progression-free survival (PFS) rate estimated at 60–70% (7,8). Upon ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0360301620343832

Intensity Modulated Radiation Therapy for Pleural ... This study aimed to evaluate the efficacy and safety of intensity modulated radiation therapy (IMRT) for pleural recurrence of thymoma that was not suitable ...

5. mskcc.org mskcc.org/cancer-care/clinical-trials/22-098

A Phase II Study of Intensity-Modulated Pleural Radiation ... Researchers are studying the safety and effectiveness of IMPRINT to one side of the chest (hemithoracic IMPRINT) to treat people with thymic cancer.

6. ascopubs.org ascopubs.org/doi/abs/10.1200/JCO.2016.67.2675

Phase II Study of Hemithoracic Intensity-Modulated Pleural ... Hemithoracic IMPRINT for malignant pleural mesothelioma (MPM) is safe and has an acceptable rate of RP. Its incorporation with chemotherapy and ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/27325859/

Phase II Study of Hemithoracic Intensity-Modulated Pleural ... Conclusions: Hemithoracic IMPRINT for malignant pleural mesothelioma (MPM) is safe and has an acceptable rate of RP. Its incorporation with ...