Phase I Study Evaluating Indomethacin in Combination With Platinum-based Chemotherapy
- Subjects with histological proven esophageal carcinoma receiving ECX (epirubicine,
cisplatin, capecitabine) (Arm I), patients receiving CAPOX (oxaliplatin,
capecitabine) (Arm II).
- Age ≥ 18 years and < 70 years.
- Platinum-based chemotherapy naïve for at least 6 months.
- Subjects with at least one evaluable lesion.
- WHO Performance Status of 0 or 1.
- Female participants should be of non-child bearing potential either physiologic or by
using adequate contraception, have a negative serum pregnancy test, and refrain from
- Written informed consent.
- Known or suspected allergy or hypersensitivity to indomethacin or any agent given in
association with this trial, in particular subjects who have a history of severe
hypersensitivity reactions to anti-emetics (5-HT3 antagonists, metoclopramide or
corticosteroids) and acetylsalicylic acid or other prostaglandin synthethase
- Symptomatic brain or meningeal tumors
- Subjects with seizure disorder requiring medication (such as corticosteroids or
- Any of the following concurrent severe and/or uncontrolled medical conditions which
could compromise participation in the study:
- Uncontrolled high blood pressure, history of labile hypertension, or history of poor
compliance with an antihypertensive regimen
- Unstable angina pectoris
- Symptomatic congestive heart failure NYHA class ≥ 3 (see appendix 13.6)
- Myocardial infarction ≤ 6 months prior to randomization
- Serious uncontrolled cardiac arrhythmia
- Active peptic ulcer disease, gastritis, inflammatory bowel disease.
- History of active gastro-intestinal bleeding
- History of cerebro-vascular disease
- Bleeding diathesis
- Chronic renal disease defined as GFR (MDRD) <60 ml/min
- Absolute Neutrophil Count (ANC) < 1.5 x 109/L (< 1500/mm3)
- Platelets (PLT) < 100 x 109/L (< 100,000/mm3)
- Hemoglobin (Hgb) < 6.0 mmol/l (patients may be transfused to achieve adequate Hb)
- Partial thromboplastin time (PTT) > 1,5 x ULN
- Serum bilirubin > 1.5 ULN
- Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) > 3.0
x ULN (> 5 x ULN if liver metastases present)
- Patients who are unable or unwilling to comply with the protocol
- Chronic treatment with a corticosteroid agent (nebulized corticosteroids are allowed)
- Patients who received radiation therapy within 4 weeks of the start of the study
- Patients who received an experimental agent less than 4 weeks before start of the
- Patients who used Omega-3/omega-6 containing products, including fish oil products
less than 2 weeks before start of the study.
- Chronic use of NSAID's and/or acetylsalicylic acid and/or other prostaglandin
- Use of anticoagulant therapy