Phase I Platinum Based Chemotherapy Plus Indomethacin (PIFA)

This is an interventional other trial for Colorectal Neoplasms focused on measuring Colorectal, Esophageal, Indomethacin, PIFA Read More

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