The primary objective is to assess the feasibility of administering adjuvant S-1 and oxaliplatin in patients with esophageal cancer after neoadjuvant chemoradiotherapy with paclitaxel and carboplatin and esophagectomy
ID
Source
Brief title
Condition
- Gastrointestinal neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The percentage of patients completing the preplanned number of 6 cycles of
SOX.
Secondary outcome
- Percentage of patients completing 6 cycles of S-1 (with or without
oxaliplatin)
- Dose modifications (i.e. delays, dose reductions, or interruptions) for S-1
- Dose modifications (i.e. delays, dose reductions, or interruptions) for
oxaliplatin
- Dose intensity of S-1.
- Dose intensity of oxaliplatin
- Toxicity
- Disease free survival
- Overall survival
Exploratory:
- Assessment of pharmacokinetics of S1 in relation to safety and efficacy.
- Potential biomarker development based on assessment of archived tumor tissue
and blood samples and the proposed mechanism of action of study drugs.
Background summary
Esophageal cancer is the 8th most common cancer and ranks sixth on the list of
cancer mortality causes. The outcome is poor with an overall 5-year survival of
10% worldwide. The incidence is rising, due to the rising incidence of
adenocarcinoma. The outcome of resectable esophagus cancer can be improved by a
multimodality treatment. Perioperative chemotherapy of gastric cancer has been
proven beneficial, however the benefit of adjuvant therapy after neo-adjuvant
chemoradiation followed by surgery in esophageal cancer is unknown. Also,
adjuvant treatment after major gastrointestinal surgery may be hard to
complete. Given the need for improvement of treatment outcomes of esopheal
cancer and the benefits of perioperative chemotherapy in gastric cancer, in
this study we will assess the feasibility of SOX as adjuvant treatment in
patients with esophageal cancer.
Study objective
The primary objective is to assess the feasibility of administering adjuvant
S-1 and oxaliplatin in patients with esophageal cancer after neoadjuvant
chemoradiotherapy with paclitaxel and carboplatin and esophagectomy
Study design
Prospective single arm feasibility study
Intervention
Adjuvant treatment with six courses of S-1 and oxaliplatin.
Study burden and risks
The main question of this study is feasibility of adjuvant chemotherapy of
esophageal tumors after surgery. Literature studies show that additional
treatment with chemotherapy around surgery from gastric cancer has a positive
effect on disease-free survival. If it is shown that it is feasible to
administer adjuvant therapy after surgery future studies can be examine whether
this affects the survival positively. Also, this study and additional research
on tumor tissue and blood may provide useful information for future patients.
It is possible that the patient experiences side effects of the chemotherapy
used. The side effects have been extensively studied in patients treated for
other types of cancer and this form of chemotherapy is generally well
tolerated. Nevertheless, if side effects are severe these can lead to
hospitalization.
The patient should come to the hospital six times over a period of 18 weeks for
the administration of oxaliplatin as wellas medical check ups. He/she also
takes in two of the three weeks of treatment tablets twice daily .
Before starting a treatment cycle blood samples will be drawn (about 5 ml each
time). Furthermore, additional blood sampling will be performed in the first
two cycles (123 ml in total, about 7-8 tablespoons) to measure the uptake and
degradation of S-1 in the body and to investigate factors that could predict
side effects and efficacy of the treatment. These additional blood samples are
taken in the hospital before the intake of S-1 and a half hour, one hour, one
and a half hours, three hours, five hours and eight hours thereafter. An
additional sample is taken in the first or second week after start of treatment
in cycle 1 and 2.
Both the blood test and the IV insertion can be painful and lead to bruising at
the puncture site.
Meibergdreef 9
Amsterdam 1105AZ
NL
Meibergdreef 9
Amsterdam 1105AZ
NL
Listed location countries
Age
Inclusion criteria
- Macroscopic radically resected adenocarcinoma of the esophagus
- Completed neoadjuvant treatment with paclitaxel 50 mg/m2 and carboplatin AUC
<= 2 on and radiotherapy to a total dose of 41.4 Gy in 23 fractions of 1.8 Gy, 5
fractions per week, with maximun one missed dose of systemic therapy, not due
to haematological toxicity
- Being able to start within 16 weeks after esophagectomy
- Age * 18 years
- WHO performance status 0-1
- Adequate bone marrow function (Hb * 6.0 mmol/L, absolute neutrophil count
*1.0 x 109/L, platelets * 100 x 109/L), renal function (serum creatinine * 1.5x
ULN and creatinine clearance, Cockroft formula, *30 ml/min), liver function
(serum bilirubin * 2 x ULN, serum transaminases * 3 x).
- Negative pregnancy test in women with childbearing potential.
- Expected adequacy of follow-up.
- Written informed consent.
Exclusion criteria
- Any history or clinical signs of metastasis
- A second malignancy interfering with the prognosis of current esophageal
carcinoma
- Known dihydropyrimidine dehydrogenase (DPD) deficiency or treatment within 4
weeks with DPD inhibitors, including sorivudine or its chemically related
analogues such as brivudine.
- - Significant cardiovascular disease < 1 yr before start of the study (as
determined by the investigator, for example: symptomatic congestive heart
failure, myocardial ischemia or infarction, unstable angina pectoris, serious
uncontrolled cardiac arrhythmia, arterial thrombosis, cerebrovascular event,
significant pulmonary embolism).
- Chronic active infection.
- Any other concurrent severe or uncontrolled disease preventing the safe
administration of study drugs.
- Any impairment of gastrointestinal function or *disease that may
significantly impair the absorption of oral drugs (i.e. uncontrolled nausea,
vomiting, diarrhoea (defined as ³CTC grade 2), malabsorption syndrome, bowel
obstruction, or inability to swallow tablets).
- Concomitant treatments: concomitant (or within 4 weeks before randomisation)
administration of any other experimental drug under investigation; concurrent
treatment with any other anti-cancer therapy.
- Continuous use of systemic immunosuppressive agents (except the use of
corticosteroids as anti-emetic prophylaxis/treatment).
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2014-003603-30-NL |
| CCMO | NL49889.018.14 |