- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT06161818
Total Neoadjuvant Therapy for Adenocarcinoma of the OESophagus and Oesophagogastric Junction: TNT-OES-2 Trial (TNT-OES-2)
Both neoadjuvant chemoradiotherapy (CROSS) and neoadjuvant chemotherapy (FLOT) have demonstrated overall survival benefit over surgery alone in esophageal and esophagogastric junction (EGJ) cancer. Despite these survival gains, the prognosis remains poor, especially in patients with nodal-positive adenocarcinoma (cN+ AC) (5-year survival 36%, compared to 55% for cN0). This highlights the need for more effective treatment options, and justifies treatment intensification in these patients.
The aim of this study is to determine the efficacy and feasibility of TNT FLOT-CROSS and TNT CROSS-FLOT in patients with resectable, cN+ AC of the esophagus or EGJ.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Bianca Mostert, MD, PhD
- Phone Number: +31107041906
- Email: b.mostert@erasmusmc.nl
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: TNT FLOT-CROSS
Patients allocated to the TNT FLOT-CROSS arm will be treated with 4 cycles of FLOT chemotherapy followed by a response evaluation consisting of a CT-scan and upper endoscopy with bite-on-bite biopsies of the primary tumor site and of any other suspected lesions in the esophagus.
Patients with distant metastases will go off-study.
All other patients will proceed to CROSS chemoradiotherapy.
|
Randomization between TNT FLOT-CROSS and TNT CROSS-FLOT
|
Experimental: TNT CROSS-FLOT
Patients allocated to the TNT CROSS-FLOT arm will be treated with CROSS chemoradiotherapy followed by a response evaluation consisting of a CT-scan and upper endoscopy with bite-on-bite biopsies of the primary tumor site and of any other suspected lesions in the esophagus.
Patients with distant metastases will go off-study.
All other patients will proceed to FLOT chemotherapy.
|
Randomization between TNT FLOT-CROSS and TNT CROSS-FLOT
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Disease-free survival
Time Frame: 24 months
|
To determine the disease-free survival after TNT (both FLOT-CROSS and CROSS-FLOT).
|
24 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Completion of therapy
Time Frame: 30 months
|
To assess the feasibility of TNT FLOT-CROSS and TNT CROSS-FLOT, defined as the proportion of patients that complete the full TNT regimens.
|
30 months
|
Overall survival
Time Frame: 24 months
|
To determine the effect of TNT FLOT-CROSS and TNT CROSS-FLOT on overall survival.
|
24 months
|
Surgery-related outcomes
Time Frame: 42 months
|
To determine the effect of TNT FLOT-CROSS and TNT CROSS-FLOT on surgery-related outcomes (i.e.
proportion that proceed to esophagectomy as planned, radical (R0) resection rate).
|
42 months
|
Therapy-related mortality and toxicity
Time Frame: 30 months
|
To determine therapy-related mortality and toxicity (according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0) of TNT FLOT-CROSS and TNT CROSS-FLOT.
|
30 months
|
30- and 90-day mortality
Time Frame: 42 months
|
To assess the effect of TNT FLOT-CROSS and TNT CROSS-FLOT on postoperative morbidity (Clavien-Dindo ≥3) and 30- and 90-day mortality.
|
42 months
|
The quality of life of patients treated with TNT FLOT-CROSS and TNT CROSS-FLOT according to the QLQ-C30
Time Frame: 42 months
|
To determine the effect of TNT FLOT-CROSS and TNT CROSS-FLOT on quality of life.
|
42 months
|
The quality of life of patients treated with TNT FLOT-CROSS and TNT CROSS-FLOT according to the QLQ-OG25
Time Frame: 42 months
|
To determine the effect of TNT FLOT-CROSS and TNT CROSS-FLOT on quality of life.
|
42 months
|
Clinical and pathological response rates
Time Frame: 42 months
|
To assess the clinical and pathological response rates after TNT FLOT-CROSS and TNT CROSS-FLOT.
|
42 months
|
Predictive biomarkers
Time Frame: 63 months
|
To collect blood at baseline, first clinical response evaluation (CRE-1), CRE-2 and postoperatively to enable future ctDNA based translational studies looking for biomarkers predictive of disease recurrence and early response.
|
63 months
|
Future ctDNA analysis
Time Frame: 63 months
|
To collect tissue at baseline, CRE-1, CRE-2 and resection to enable future ctDNA based translational studies looking for biomarkers predictive of disease recurrence and early response.
|
63 months
|
Collaborators and Investigators
Sponsor
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- TNT-OES-2
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Esophageal Cancer
-
OHSU Knight Cancer InstituteOregon Health and Science UniversityWithdrawnStage IIB Esophageal Cancer AJCC v7 | Stage III Esophageal Cancer AJCC v7 | Stage IIIA Esophageal Cancer AJCC v7 | Stage IIIB Esophageal Cancer AJCC v7 | Stage IIIC Esophageal Cancer AJCC v7
-
National Cancer Institute (NCI)NRG OncologyCompletedEsophageal Adenocarcinoma | Gastroesophageal Junction Adenocarcinoma | Stage IIA Esophageal Cancer AJCC v7 | Stage IIB Esophageal Cancer AJCC v7 | Stage IIIA Esophageal Cancer AJCC v7 | Stage IIIB Esophageal Cancer AJCC v7 | Stage IB Esophageal Cancer AJCC v7United States
-
AIO-Studien-gGmbHBristol-Myers SquibbCompletedEsophageal Cancer | Gastrooesophageal Cancer | Oesophageal Cancer | GastroEsophageal Cancer | Esophageal Cancers NOS | Oesophageal Cancer Metastatic | Esophageal Cancer Metastatic | Oesophageal Cancer NosGermany
-
Cancer Institute and Hospital, Chinese Academy...Tianjin Medical University Cancer Institute and Hospital; Sichuan Cancer Hospital...UnknownEsophageal Neoplasm | Esophageal Cancer TNM Staging Primary Tumor (T) T3 | Esophageal Cancer TNM Staging Primary Tumor (T) T2 | Esophageal Cancer TNM Staging Regional Lymph Nodes (N) N0 | Esophageal Cancer TNM Staging Distal Metastasis (M) M0China
-
University of Wisconsin, MadisonActive, not recruitingResectable Esophageal Cancer | GastroEsophageal CancerUnited States
-
Academisch Medisch Centrum - Universiteit van Amsterdam...UMC UtrechtCompletedEsophageal Cancer, Stage II | Esophageal Cancer Stage IIINetherlands
-
Tianjin Medical University Cancer Institute and...The First Affiliated Hospital with Nanjing Medical University; The First Affiliated... and other collaboratorsUnknownEsophageal Cancer Stage III | Esophageal Cancer Stage IIBChina
-
Tianjin Medical University Cancer Institute and...Sun Yat-sen University; Cancer Institute and Hospital, Chinese Academy of Medical... and other collaboratorsNot yet recruitingStage III Esophageal Cancer | Stage II Esophageal Cancer
-
Tianjin Medical University Cancer Institute and...UnknownStage III Esophageal Cancer | Stage II Esophageal CancerChina
-
National Cancer Institute (NCI)RecruitingNeoplasms | Esophageal Neoplasms | Esophagus Cancer | Esophagus Neoplasm | Neoplasms, Esophageal | Esophageal Cancer (EsC)United States
Clinical Trials on FLOT-CROSS or CROSS-FLOT
-
The Affiliated Nanjing Drum Tower Hospital of Nanjing...Unknown
-
Jagiellonian UniversityRecruiting
-
Ruijin HospitalCompletedGastric Cancer | Chemotherapy EffectChina
-
Institut für Klinische Krebsforschung IKF GmbH...Trium Analysis Online GmbHCompletedStomach Cancer | Gastroesophageal Junction CancerGermany
-
Henan Cancer HospitalUnknownAdenocarcinoma of the Stomach / GastroesophagealChina
-
Keio UniversityRecruitingEsophageal Squamous Cell CarcinomaJapan
-
Royal Marsden NHS Foundation TrustMerck KGaA, Darmstadt, GermanyActive, not recruitingGastric Adenocarcinoma | Oesophageal AdenocarcinomaUnited Kingdom
-
University Hospital, MontpellierRecruiting
-
University of KielRecruiting
-
Koya Medical, Inc.CompletedLymphedema | Venous Insufficiency | Chronic Venous Insufficiency | Lymphedema, Lower Limb | Lymphedema of LegUnited States