Intrathoracic Chemotherapy for TETs With Pleural Spread or Recurrence (CHOICE-2)

Fudan University

Status

Not yet enrolling

Conditions

Thymic Epithelial Tumor

Treatments

Procedure: Surgery+HITOC

Procedure: Surgery alone

Study type

Interventional

Funder types

Other

Identifiers

NCT07383142

CHOICE-2

Details and patient eligibility

About

Hyperthermic intrathoracic chemotherapy (HITOC) offers a strategy to eliminate microscopic residual disease after surgical resection. Especially it is investigated to improve long-term survival in thymic epithelial tumors with pleural dissemination or recurrence. A prospective, multicenter, randomized phase III clinical trial (CHOICE-2) is conducted to compare the efficacy and safety of surgery combined with HITOC versus surgery alone. The HITOC regimen involves intrathoracic perfusion with doxorubicin on postoperative day 1 and cisplatin on postoperative day 2.

Full description

Thymic epithelial tumors (TETs) frequently manifest with or recur as pleural dissemination (Stage IVa), presenting a significant clinical challenge. Although cytoreductive surgery is the cornerstone of treatment, achieving complete elimination of microscopic residual disease remains difficult, often leading to subsequent recurrence. Hyperthermic intrathoracic chemotherapy (HITOC) has emerged as a promising adjuvant strategy to control local disease by combining the cytotoxic effects of chemotherapy with hyperthermia to eradicate microscopic residuals.

Building on the favorable safety and efficacy results from the Phase II CHOICE study, the CHOICE-2 study is a prospective, multicenter, randomized, phase III clinical trial designed to compare surgery combined with HITOC versus surgery alone. A total of 202 eligible participants with pleural dissemination or pleural recurrence of TETs will be randomized in a 1:1 ratio into two arms.

Participants in the experimental arm will undergo lung-preserving cytoreductive surgery (pleurectomy/decortication or extended pleurectomy/decortication) followed by HITOC. The HITOC regimen involves intrathoracic perfusion with doxorubicin (25 mg/m²) on postoperative day 1 and cisplatin (50 mg/m²) on postoperative day 2, utilizing a perfusion system heated to 43°C for 60 minutes. Participants in the control arm will receive the same standard surgical resection without HITOC.

The primary objective is to evaluate the 3-year progression-free survival (PFS) rate. Secondary endpoints include overall survival (OS), myasthenia gravis (MG) remission rates according to MGFA criteria, and the incidence of perioperative complications.

Enrollment

202 estimated patients

Sex

All

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Age range: 18-75 years old; Expected survival time > 12 months; Preoperative imaging (CT, MRI, or PET-CT) clinically diagnosed as TETs
Patients with de novo stage IVa thymoma (DNT) diagnosed by the multidisciplinary team (MDT) are eligible if deemed suitable for surgery under any of the following conditions: (1) candidates for primary surgery without contraindications; (2) candidates for staged surgery who have completed phase I surgery and are reassessed by the MDT as eligible for phase II surgery 3 months postoperatively; or (3) patients initially requiring induction therapy, provided the diagnosis is pathologically confirmed by biopsy, induction therapy is administered according to TET guidelines, imaging and laboratory evaluations are performed 4-6 weeks after completion of therapy, and the MDT confirms the absence of surgical contraindications upon re-evaluation.
For patients with thymoma with pleural recurrence (TPR), the initial surgery must have achieved complete resection without evidence of pleural dissemination or intraoperative tumor rupture, and the interval between the first surgery and the development of pleural metastasis must be longer than 6 months.
According to the definition of T1-3NxM1a stage, no intrapericardial dissemination, no intrapulmonary parenchymal metastatic nodules, no distant organ metastasis (M1b)
During the operation, the pleural nodules were removed. The frozen section pathology during the operation confirmed that the pleural nodules were TETs pleural metastatic nodules.
No history of other malignant tumors, except for patients who had prior malignancies treated with curative surgery, were confirmed to have pathologic stage I disease requiring no adjuvant therapy (e.g., resected pulmonary ground-glass opacity or papillary thyroid carcinoma) and have remained free of recurrence for more than 5 years.
ASA stage I/II
Be able to understand the situation of this study and sign the Informed Consent form.

Exclusion criteria

Preoperative imaging examinations such as CT, MRI or PET-CT, or intraoperative exploration revealed that the tumor involved the ascending aorta, aortic arch, descending aorta, intrapericardial pulmonary vessels, heart, trachea or esophagus (T4), or had dissemination within the pericardium (M1a) or hematogenous metastasis (M1b stage);
Within 4-6 weeks after completion of induction therapy (chemotherapy, radiotherapy, immunotherapy, or targeted therapy), imaging studies (CT or PET-CT) and laboratory evaluations (complete blood count, liver and renal function, cardiac biomarkers, and thyroid function) were performed by the mediastinal MDT to assess surgical eligibility; patient found to have surgical contraindications and deemed unsuitable for surgery or HITOC were excluded;
The diagnosis was confirmed by biopsy or puncture as a non-TETs type (such as lymphoma, neurogenic tumor, germ cell tumor, thymic lipoma, thymic sarcoma or neuroendocrine tumor);
The patient had a history of multiple surgeries in the past (≥2), the initial surgery of TPR was palliative resection, and pleural dissemination was a iatrogenic implantation site; or the patient received a radiotherapy dose greater than 60 Gy before enrollment;
Had other active malignant tumors, or had received anti-tumor treatment (chemotherapy, radiotherapy, immunotherapy, small molecule targeted therapy or other anti-tumor biological agents) for other malignant tumors in the past;
The patient had myasthenia gravis in an unstable state or during an acute exacerbation;
Had the following major cardiovascular disease histories: congestive heart failure, poorly controlled angina pectoris, transmural myocardial infarction, high-risk arrhythmia, significant valvular disease or poorly controlled hypertension, cardiovascular compensatory dysfunction;
The patient had a weight loss of more than 5 kg within the past one month; severe uncontrolled systemic systemic diseases, such as active infection or poorly controlled diabetes; patients with bleeding disorders and those with bleeding tendencies; patients with abnormal coagulation function, with bleeding tendencies or undergoing thrombolysis or anticoagulation treatment; patients with grade II-IV bone marrow suppression;
The patient had a history of thoracic surgery due to tuberculous pleurisy or mesothelioma, and the contralateral lung atrophy involved one or more lung lobes or more than one lung lobe;
The patient had an allergy history to cisplatin or doxorubicin drugs;
Had a history of organ transplantation (including autologous bone marrow transplantation and peripheral stem cell transplantation); Had a history of mental disorders, neurological diseases or other central nervous system diseases affecting compliance;
The patient was in the acute inflammatory stage due to bacterial, viral or other pathogenic microorganism infection; Had active infection of immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) or known HIV seropositivity;
Pregnant or lactating women, and fertile men and women who were unwilling to use adequate contraceptive measures during treatment;
The patient had received grade IV surgical treatment within 2 months or was in a recovery state due to other diseases or was in the intervention period of other research projects.