Combination of chemoTherapy aNd chemoradioTherapy for adenocarcinoma of the OESophagus and gastro-oesophageal junction with oligometastatic disease
- Conditions
- Adenocarcinoma of the oesophagus or gastro-oesophageal junction
- Registration Number
- NL-OMON23939
- Lead Sponsor
- Erasmus MC
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- 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.
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
13. Language difficulty, dementia or altered mental status prohibiting the understanding and
giving of informed consent and to complete quality of life questionnaires;
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Primary endpoint is the tolerability of the combined regimens, defined as the number of patients that complete the administration of 4 x FLOT and the full CROSS CRT regimen.
- Secondary Outcome Measures
Name Time Method Secondary eindpoints are the number of patients that have progressive disease after four cycles of FLOT CT, disease control rate (DCR) and objective response rate (ORR), both according to RECIST 1.1, serious adverse events and adverse events according to Common Terminology Criteria for Adverse Events (CTCae) v4.0, cumulative administered dose of FLOT and number of cycles of carboplatin/paclitaxel administered as part of CROSS CRT, progression free survival [PFS], overall survival [OS], number of patients with a clinically complete response, QoL, the number of patients proceeding to local therapy of distant metastases and/or oesophagectomy.