Pharmacokinetic Study of CPT-11, Raltegravir and Midazolam With Characterisation of UGT1A1 Genotype

• Status: Completed
• Trial end date: 2012-02-01
• Target enrollment: 0
• Participant gender: All

Summary

The objectives of this study are:

To correlate pharmacokinetic parameters of raltegravir and midazolam with irinotecan (CPT-11) and its metabolite SN-38.

To correlate the genotype of UGT1A1 of patients receiving CPT-11 chemotherapy with irinotecan and raltegravir pharmacokinetic parameters.

To model pharmacokinetic and pharmacodynamic behaviour of CPT-11 in the study population.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National University Hospital, Singapore
• Treatments: Irinotecan; Midazolam; Raltegravir Potassium

Criteria

Inclusion Criteria:

• Histologically or cytologically proven solid tumour for which CPT-11 given by the Folfiri regimen is indicated and prescribed by the attending physician.

• Age above 21 years.

• Measurable or evaluable disease

• Karnofsky performance status > 70%

• Life expectancy > 3 months

• WBC > 3.0 x 103/?l; ANC > 1500/?l

• Hemoglobin > 9.0 g/dl

• Platelets > 100000/?l

• Creatinine < 1.5 x ULN or calculated creatinine clearance > 40 ml/min

• Total bilirubin < 1.5 x ULN

• SGOT, SGPT < 5 x ULN unless due to disease

Exclusion Criteria:

• Biologic therapy or chemotherapy within 4 weeks. (Six weeks for prior nitrosoureas or mitomycin C).

• Radiation therapy within 4 weeks if > 25% of bone marrow was irradiated.

• Have not received any medications that are known to be metabolised by UGT1A1 within 30 days of the first dose of CPT-11.

• Short gut syndrome or other causes of malabsorption.

• Colony stimulating factors within 2 weeks.

• Women of childbearing potential not practicing birth control. (Note: by means other than oral contraception)

• Pregnant women

• Severe peripheral neuropathy grade 2 or higher.

• Medical or psychiatric conditions which may impair the patient's ability to provide informed consent.

• Hypersensitivity to CPT-11, raltegravir or midazolam/other benzodiazepines.

• Rapidly progressive intracranial or spinal metastatic disease.