Phase I study evaluating indomethacin in combination with platinum-based chemotherapy

Completed

• Conditions: Cancer; malignancy; 10017991

• Registration Number: NL-OMON45105
• Lead Sponsor: niversitair Medisch Centrum Utrecht

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 29 April 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 18

Inclusion Criteria

- Subjects with a histological proven malignancy receiving cisplatinum combined with gemcitabine or 5FU/capecitabin (dose range cisplatin 60-80 mg/m2) (Arm I) or CAPOX (oxaliplatin, capecitabine) (Arm II) in a 21 day cycle.
- Platinum*based chemotherapy naïve for at least 6 months.
- Age * 18 years.
- 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 synthethase inhibitors.
- Symptomatic brain or meningeal tumors
- Subjects with seizure disorder requiring medication (such as steroids 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 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 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 synthethase inhibitors.
- Use of anticoagulant therapy

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Primary endpoints: Safety of the combination of platinum-based therapy and<br /><br>indomethacin. </p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Secondary endpoints: Pharmacodynamics of the combination of platinum-based<br /><br>chemotherapy and indomethacin. Efficacy. Tolerability.</p><br>