Chemotherapy followed by chemoradiotherapy for metastatic esophageal cancer
- Conditions
- Patients (18 – 75 years) who are diagnosed with adenocarcinoma of the oesophagus or GOJ with a resectable primary tumour and de-novo synchronous oligometastatic disease.Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-003605-55-NL
- Lead Sponsor
- Erasmus MC - University Medical Centre
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 20
In order to be eligible to participate in this study, a subject must meet all of the following criteria:
1.Histologically-proven, resectable adenocarcinoma of the oesophagus or GOJ according to the UICC TNM7 definition (appendix 2). Tumours of the oesophagus and tumours of which the epicentre is within 5 cm of the GOJ are eligible for inclusion in the trial in the case of adenocarcinomatous histology (Type 1 and Type 2 according to Siewert classification of oesophagogastric adenocarcinoma)
2.Pre-treatment stage cT1N+ M1 or cT2-4a N0/N+, M1 (In case of stage cT4a, curative resectability has to be explicitly verified by the multidisciplinary tumour board.
3.Oligometastatic disease, which for this study is defined as a maximum of four resectable/treatable metastatic lesions. These four lesions can be present in a maximum of two organs (liver, lung, bones, or adrenal gland). Lymph nodes are not counted as an organ. If metastatic retroperitoneal or supraclavicular lymph nodes are present, this lymph node site counts as one metastatic lesion, and together with the possible metastases in organs cannot exceed the four lesions.
4. Age?=?18 years, <75 years.
5. No prior abdominal, thoracic or cervical radiotherapy overlapping with the CROSS irradiation fields.
6.No prior cytotoxic chemotherapy
7.Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (see Appendix 1)
8.Adequate cardiac function (cardiac function tests such as echocardiography only necessary in symptomatic patients).
9.Adequate respiratory function (pulmonary function tests only necessary in symptomatic patients)
10.Adequate bone marrow function (White Blood Cells >3x10^9/l; Haemoglobin?mmol/L; platelets >100x10^9/l). In the event of transfusions, the last red blood cell transfusion should be more than 2 weeks before inclusion.
11.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
12.Written informed consent and ability to understand the nature of the study and the study-related procedures and to comply with them
13.Women of child-bearing potential must have a negative serum pregnancy test during screening period.
14.Patients must be willing to use adequate contraception during the study and for 3 months after the end of the study.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 10
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10
A potential subject who meets any of the following criteria will be excluded from participation in this study:
1.Patients with tumours of squamous, adenosquamous or other non-adenocarcinoma histology
2.Patients with advanced irresectable or extensive metastatic oesophageal adenocarcinoma (involving 3 or more organs or more than 4 metastatic lesions)
3.Patients with overt peritoneal dissemination, as detected on PET-CT or regular CT-scan. In patients in whom a diagnostic laparoscopy is indicated, tumour-positive cytology peritoneal fluid is also an exclusion criterion
4.Oesophageal adenocarcinoma evaluated as not curatively-resectable by the multidisciplinary tumour board , for instance because ingrowth in the trachea
5.Gastric carcinoma (according to UICC TNM7)
6.Clinically significant (active) cardiac disease (e.g. symptomatic coronary artery disease or myocardial infarction within last 12 months)
7.Clinically significant lung disease (Forced Expiratory Volume in one second (FEV1) <1.5 l)
8.Peripheral neuropathy grade >1 according to CTCae v4.0
9.Pregnant and lactating women, or patients of reproductive potential who are not using effective birth control methods. If barrier contraceptives are used, they must be continued by both sexes throughout the study.
10.Participation, current or during the last 30 days prior to informed consent, in another intervention trial with interference to the chemotherapeutic or chemoradiotherapeutic intervention of this study
11.Expected lack of compliance with the protocol
12.Secondary primary cancer with the exclusion of basal cell carcinoma of the skin
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To assess the safety and feasibility of a multimodal (combination of four cycles of FLOT CT and CROSS CRT) treatment regimen for patients with adenocarcinoma of the oesophagus or GOJ with limited distant metastatic disease.;Secondary Objective: •To assess 1-year disease control rate (DCR) and objective response rate (ORR), both according to RECIST v1.1<br>•To assess progression free survival and overall survival<br>•To assess the number of patients with a clinically complete response<br>•To evaluate QoL parameters (especially dysphagia, odynophagia, fatigue, and weight loss)<br>•To assess the number of patients who proceed to local treatment of distant metastases or primary tumour. <br>;Primary end point(s): Primary endpoint is the tolerability of the combined regimens, defined as the number of patients that complete the administration of 4 x FLOT and CROSS CRT. ;Timepoint(s) of evaluation of this end point: At completion of both 4X FLOT and CROSS CRT
- Secondary Outcome Measures
Name Time Method