Phase I Platinum Based Chemotherapy Plus Indomethacin

Inclusion Criteria:

* Subjects with a histological proven malignancy receiving cisplatin combined with gemcitabine or 5FU/capecitabine. (cisplatin dose range 60-80 mg/m2) (Arm I) or CAPOX (oxaliplatin, capecitabine) (Arm II) in a 21 day cycle.
* Age ≥ 18 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 breast feeding.
* Written informed consent.

Exclusion Criteria:

* 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 synthetase inhibitors.
* Symptomatic brain or meningeal tumors
* Subjects with seizure disorder requiring medication (such as corticosteroids or anti-epileptics).
* 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 gastrointestinal bleeding
* History of cerebrovascular 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 study.
* 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 synthetase inhibitors.
* Use of anticoagulant therapy