Total Neoadjuvant Therapy for Adenocarcinoma of the OESophagus and Oesophagogastric Junction: TNT-OES-2 Trial

Launched by ERASMUS MEDICAL CENTER · Nov 29, 2023

Keywords

ClinConnect Summary

The TNT-OES-2 trial is a clinical study looking at new treatment options for patients with adenocarcinoma, a type of esophageal cancer, especially those with cancer that has spread to nearby lymph nodes. The researchers want to see if a combination of two treatment approaches, known as TNT FLOT-CROSS and TNT CROSS-FLOT, can improve the chances of survival before surgery compared to standard treatments. This trial is important because, while current treatments have helped some patients live longer, those with certain types of cancer still have a poor outlook, making it necessary to explore stronger treatment options.

To be eligible for this trial, participants should be adults aged 18 to 74 who have a specific stage of resectable adenocarcinoma of the esophagus or the area where the esophagus meets the stomach. They should not have received previous chemotherapy for this type of cancer and should meet certain health criteria, such as having good heart and lung function. If you join this trial, you can expect to receive closely monitored treatments and take part in evaluations to see how well the new therapies work. It's also important to know that the trial is not yet recruiting participants, so it will start enrolling people in the near future.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • Patients with cT2-4aN+M0 resectable adenocarcinoma of the esophagus or EGJ (Siewert type I-II) according to the 8th edition of the Union for International Cancer Control (UICC) TNM classification for Esophageal Cancer who are planned to undergo nCRT. In case of stage cT4a, curative resectability has to be explicitly verified by the multidisciplinary tumor board. Clinical N+ status should be determined by EUS or 18F-FDG PET/CT.
• • Maximum of 4 cm ingrowth in the cardia, measured by upper endoscopy.
• • In case of tumor and/or lymph node involvement below the diaphragm, the most proximal involved lymph node station cannot be higher than N7.
• • In case of no tumor or lymph node involvement below the diaphragm, the most proximal involved lymph node station cannot be higher than N4.
• • Age ≥ 18 years and \<75 years.
• • No prior abdominal, thoracic or cervical radiotherapy overlapping with the CROSS irradiation fields.
• • No prior cytotoxic chemotherapy for esophageal cancer.
• • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1 (28).
• • Weight loss \<10%.
• • Adequate cardiac and respiratory function (cardiac or pulmonary function tests such only necessary in symptomatic patients).
• • Adequate bone marrow function (White Blood Cells \>3x109/L; Hemoglobin \>5.5 mmol/L; platelets \>100x109/L). In the event of transfusions, the last red blood cell transfusion should be more than 2 weeks before inclusion.
• • Adequate renal function (Glomerular Filtration Rate \>50 ml/min) or serum creatinine ≤1.5 x upper limit of normal (ULN) and adequate liver function (total bilirubin \<1.5x Upper Level of Normal (ULN); Aspartate transaminase (AST) \<2.5x ULN and Alanine transaminase (ALT) \<3x ULN.
• • A negative serum pregnancy test in women of child-bearing potential during screening period.
• • Use of adequate contraception during the study up to 3 months after the end of the study.
• • Written informed consent and ability to understand the nature of the study and the study-related procedures and to comply with them.
• Exclusion Criteria:
• • Patients with tumors of squamous, adenosquamous or other non-adenocarcinoma histology.
• • Patients who are eligible for the TRAP-2 trial (NCT05188313, i.e. HER2-positive tumor and no contra-indication for anti-HER2 treatment).
• • Patients with overt hematogenous (organ) metastasis, distant lymphatic metastases (cervical/retroperitoneal), peritoneal or pleural dissemination, as detected on 18F-FDG PET/CT or regular CT-scan. In patients in whom a diagnostic laparoscopy is indicated (to assess resectability or to exclude peritoneal disease), tumor-positive cytology peritoneal fluid is also an exclusion criteria.
• • Clinically significant (active) cardiac disease (e.g. symptomatic coronary artery disease of myocardial infarction within the last 12 months) or lung disease (forced expiratory volume in one second (FEV1) \<1.5L).
• • Peripheral neuropathy grade \>1, according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (18).
• • Homozygous DPYD genotype (tested for \*2A, \*13, 2846A\>T, and 1236G\>A).
• • Pregnant and lactating women, or patients of reproductive potential who are not using effective contraception. If barrier contraceptives are used, they must be continued by both sexes throughout the study.
• • Other active malignancies with a prognosis interfering with that of esophageal cancer.
• • Expected lack of compliance with the protocol.
• • Language difficulty, dementia or altered mental status prohibiting the understanding and giving of informed consent and to complete quality of life questionnaires.