Intrathoracic Chemotherapy for TETs With Pleural Spread or Recurrence

Study Overview
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Brief Summary
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Hyperthermic intrathoracic chemotherapy (HITOC) offers an additional treatment option for malignant pleural tumors after surgical cytoreduction. Especially it is used to further improve local tumor control in thymic malignancies with pleural spread, who underwent multimodality therapy including surgical resection. A phase II clinical study was conducted to explore the efficacy and safety of surgery followed by HITOC (POD1: DOX, POD2: cisplatin) for thymic epithelial tumors with pleural spread or recurrence.

Official Title
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Cytoreductive Surgery and Hyperthermic Intrathoracic Chemotherapy for the Treatment of Thymic Epithelial Malignancies With Pleural Spread or Recurrence (CHOICE): a Prospective, Open, Single-arm Study Choice

Conditions
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Thymic Epithelial Tumor

Intervention / Treatment
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* Procedure: HITOC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Puncture biopsy, thoracoscopic/mediastinal biopsy, or surgery to confirm pathologically thymic epithelial tumor (TETs) Imaging examination shows TETs with pleural spread or recurrence, and the mediastinal MDT team considers HITOC suitable. Patients with ≥16 and ≤80 years old. ASA I-II. The patients should have no functional disorders in the main organs. There was no history of other malignant carcinomas. The duration from the last chemotherapy was >4 weeks, the duration from the last radiotherapy was >6 weeks, and the duration from the last immunotherapy was >6 weeks. Not allergic to cisplatin or doxorubicin. The patients should be able to understand our research and sign the informed consent. Exclusion Criteria: Imaging or pathological examination shows TETs without pleural spread or recurrence, or with pericardial dissemination or extrathoracic metastasis. Patients with lymphoid system, neurogenic or reproductive system carcinoma. Patients who have been receiving chemotherapy, radiotherapy, immunotherapy, or targeted therapy. Patients with myasthenia gravis in unstable or acute exacerbation stage. The patients have been proven history of congestive heart failure, angina without good control with medicine; ECG-proved penetrating myocardial infarction; hypertension with bad control; valvulopathy with clinical significance; arrhythmia with high risk and out of control. The patients have the severe systematic intercurrent disease, such as active infection or poorly controlled diabetes; coagulation disorders; hemorrhagic tendency or under-treatment of thrombolysis or anticoagulant therapy. Female who is positive for a serum pregnancy test or during lactation period. The patients have a history of organ transplantation (including autologous bone marrow transplantation and peripheral stem cell transplantation. The patients have a history of peripheral nerve system disorders, obvious mental disorders, or central nerve system disorders. The patients attend other clinical trials.

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: A Prospective single-arm Study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: HITOC<br>HITOC group contains all patients who undergo HIROC in this study. | Procedure: HITOC<br>* Doxorubicin(dose: 25mg/m2) + Cisplatin(dose: 50mg/m2).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative hospital stay | Postoperative hospital stay is the duration for every enrolled patient until the date of meeting the criteria of hospital discharge since the date of surgery. The criteria of hospital discharge were defined as with the volume of postoperative drainage < 200 ml/day, a normal chest X-ray, and good physical condition. | Up to the date of meeting the criteria of hospital discharge since the data of surgery, up to 1 month | 
| treatment-related adverse events and complications | Number and severity of adverse events that are related to the treatment of each patient. Postoperative treatment-related complications were assessed by the Clavien-Dindo Classification. Treatment-related adverse events as assessed by CTCAE v5.0. | Up to the date of meeting the criteria of hospital discharge since the data of surgery, up to 1 month | 
| EORTC QLQ-C30 score for overall quality of life | Overall quality of life is respectively evaluated at randomization and 1 month, 3 month, 6 month after surgery among patients by using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C-30 Scale (EORTC QLQ-C30) (V3.0). The minimum value of EORTC QLQ-C30 score was 0， and the maximum was 100. Zero indicates the worst quality of life, while 100 represents the best quality of life. | Up to the end of follow-up since the date of randomization, up to 6 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual Analog Scales scores for postoperative pain | the cumulative daily pain score at rest using VAS from postoperative 0 to 72 hours. The minimum value of the VAS score was 0，and the maximum was 10. Zero indicates the least painful, while 1 represents the worst. The smaller (larger) cumulative daily pain score represents the less (more) pain. | from 0 to 72 hours after surgery | 
| Volume of postoperative drainage | The volume of postoperative drainage of the patient was the sum of his daily drainage volume after the surgery. The types of drainage equipment include the thorax close drainage equipment and the unidirectional negative-pressure drainage ball. | Up to the date of removal of drainage equipment since the data of completion of surgery, up to 7 days | 
| Progression-free survival (PFS) | the duration from the date of S-HITOC to the date of the first progression. Disease progression is defined as locoregional (anterior mediastinal area, lung, pericardiac metastasis or pleural progression) or metastatic (supraclavicular lymph nodes or distant organs). | Through study completion, an average of 5 year | 
| Overall survival (OS) | the duration from the date of S-HITOC to the date of the death. | Through study completion, an average of 5 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hyperthermic Intrathoracic Chemotherapy, Thymic Epithelial Malignancies