Cancer Cancer Malignant neoplasm without specification of site
Conditions
Interventions
1. Single midazolam clearance test (MCT), involving midazolam infusion and pharmacokinetic measurements
2. Regular laboratory testing prior to irinotecan infusion, and weekly outpatients controls
3. I
Sponsors
Erasmus Medical Centre (Netherlands)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histological or cytological confirmed diagnosis of any form of cancer, which is thought to be sensitive to irinotecan-treatment 2. Aged 18 years or older, either sex 3. World Health Organization (WHO) performance status 0 or 1 4. Adequate haematological functions, as determined 2 weeks before inclusion and within 2 days before start of irinotecan infusion (neutrophil count greater than 2.0 x 10^9/l, platelets greater than 100 x 10^9/L) 5. Adequate renal and hepatic functions, as determined 2 weeks before inclusion and within 2 days before start of irinotecan infusion (bilirubin less than 1.25 x upper limit of normal [ULN]; serum glutamic oxaloacetic transaminase [SGOT]/serum glutamic pyruvate transaminase [SGPT] less than 2.5 x ULN, in case of liver metastasis less than 5 x ULN; serum creatinine less than 1.25 x ULN; alkaline phosphatase [AP] less than 5 x ULN; gammaGT less than 200 U/l) 6. Written informed consent 7. Complete workup within 2 weeks prior to chemotherapy
Exclusion criteria
Exclusion criteria: 1. Pregnant or lactating patients 2. Other serious illness or medical unstable conditions requiring treatment 3. Symptomatic central nervous system (CNS) metastases 4. History of psychiatric disorder 5. Time between last anti-tumour chemotherapy treatment and first day of irinotecan therapy less than 4 weeks 6. Radiotherapy within 4 weeks before chemotherapy, unless less than 20% of bone marrow area is involved 7. (Recent) radiotherapy at abdomen 8. Major surgery within 4 weeks before study entry 9. Unresolved bowel obstruction or chronic colic disease 10. Use of, and unwillingness to abstain from grapefruit (juice), herbal supplements/tea/over the counter medicines during the study period (starting 3 weeks before the first course). (Chronic) use of CYP3A and Pgp inhibiting/inducing medication, dietary supplements, or other inhibiting compounds.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pharmacokinetics (AUC/clearance) of midazolam, irinotecan and metabolite SN-38, determined by LC-MS-MS and calculated using WinNonlin, measured during the infusion period and for the next 3 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Toxicity assessment (i.e. leukopenia, neutropenia, neutropenic fever, diarrhoea), measured during the infusion period and for the next 3 weeks | — |
Countries
Netherlands
Outcome results
None listed