Influence of Medicinal Cannabis (Bedrocan) on the pharmacokinetics of irinotecan and docetaxel in cancer patients (METC 2003-171 Erasmus MC).

• Register: Netherlands Trial Register
• Last refreshed on: 28 April 2013
• Main ID: NTR783
• Date of registration: 26/09/2006
• Primary sponsor: Erasmus Medical Center - Daniel den Hoed Kliniek, afdeling Interne Oncologie
• Public title: Influence of Medicinal Cannabis (Bedrocan) on the pharmacokinetics of irinotecan and docetaxel in cancer patients (METC 2003-171 Erasmus MC).
• Scientific title: N/A - N/A
• Date of first enrolment: 1/1/2004
• Target sample size: 24
• Recruitment status: complete
• URL: http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=783
• Study type: intervention
• Study design: Randomised: No; Masking: None; Control: Not applicable; Group: Crossover; Type: [default]

Countries of recruitment

The Netherlands

Contacts

• Name: J. Verweij

• Name: F.A. Jong, de

Key inclusion & exclusion criteria

Inclusion criteria: 1. Histological or cytological confirmed diagnosis of any form of (metastatic) cancer;

1.1 which is refractory to conventional treatment; or

1.2 for which no other (effective) treatment options are available.

2. Age 18 years and older.

3. WHO performance 2 or less (see appendix).

4. Adequate hematological functions (absolute neutrophil count > 2.0x109/L, platelets > 100x109/L).

5. Adequate renal and hepatic functions: bilirubin < 1.25xULN; SGOT and SGPT < 2.5xUNL, in case of liver metastasis < 5xUNL; serum creatinine < 1.25xULN; AP £ 5xULN; patients with SGPT and/or SGOT > 1.5xULN associated with AP > 2.5xULN are not eligible for the docetaxel arm.

6. Written informed consent.

7. Complete initial work-up within two weeks prior to chemotherapy.

8. Willingness to abstain from grapefruit, grapefruit juice, herbal dietary supplements, and herbal tea during the study period (starting 3 weeks before the first course).

9. Willingness to abstain from alcohol, car-driving, use of dangerous instruments and machinery or engagement in hazardous activity during the time of medicinal cannabis-use because of (non-excludable) interference with logical thinking, ability to concentrate, and response speed.

Exclusion criteria: 1. Pregnant or lactating patients; patients with reproductive potential must use a reliable method of contraception (excluding oral contraceptives), if required.

2. Symptomatic CNS metastases.

3. Other serious illness or medical unstable condition requiring treatment or history of psychiatric disorder that would prohibit the understanding and giving of informed consent.

4. Time between last anti-tumor chemotherapy treatment and first day of irinotecan or docetaxel therapy less than 4 weeks, provided that the patient has recovered from all relevant toxic effects.

5. Radiotherapy within the last 4 weeks before chemotherapy, unless < 20% of the bone marrow area is involved.

6. Major surgery within 4 weeks before study entry (to be determined by an MD).

7. History of alcohol or drug abuse, including current substance dependence, methadone maintenance.

8. Use of St John?s wort and/or other herbal medicines within 4 weeks before study entry.

9. Current cannabis use and/or history of marijuana/cannabis abuse.

10. (Chronic) use of CYP3A inhibiting medication, dietary supplements or other inhibiting compounds.

11. (Chronic) use of CYP3A inducing medication, dietary supplements or other inducing compounds.

12. Unwillingness to change medication, or no adequate alternatives available, when drugs known to interact with CYP3A isozymes, are taken.

13. History of serious depression, schizophrenia, or psychosis.




Additionally for irinotecan patients:

1. Unresolved bowel obstruction or chronic colic disease.

2. Radiotherapy at abdomen.



Age minimum:
Age maximum:
Gender:

Health Condition(s) or Problem(s) studied

Cancer

Intervention(s)

Course 1 irinotecan: patients will be treated with 600 mg irinotecan given as a 90-minute intravenous infusion in 250 ml NaCl 0.9% (t=0, day 1, course 1).

Course 1 docetaxel: patients will be treated with 180 mg docetaxel given as 1-hour intravenous infusion in 250 ml NaCl 0.9% (t=0, day 1, course 1).




As an (extra) safety assessment, pharmacokinetic profiles will be determined before day 7 of course 1. Only patients who do not develop abnormal toxicity or an abnormal pharmacokinetic profile and for whom no dose reduction due to an increased risk for toxicity would have been necessary (if a second course of irinotecan or docetaxel without cannabis were to be given), will be further treated according to the study protocol. The decision to further treat a patient according to the study protocol will be made by the responsible physician and the study coordinators and will take prior to the start of the medicinal cannabis treatment). Patients who remain included in the study will receive medicinal cannabis during 15 days, as described [25], starting on day 10, course 1. On day 1, course 2 (i.e. day 22) the second course of docetaxel or irinotecan will be given. The last 3 days of medicinal cannabis will thus be given during the second course of chemotherapy (i.e. day 1-3, course 2).




Course 2 irinotecan: patients will be treated with 450 mg irinotecan given as a 90-minute intravenous infusion in 250 ml NaCl 0.9% (t=0, day 1, course 2).

Course 2 docetaxel: patients will be treated with 135 mg docetaxel given as 1-hour intravenous infusion in 250 ml NaCl 0.9% (t=0, day 1, course 2).




For safety reasons, a 25% dose reduction will be applied during the combination therapy in at least the first three irinotecan and the first three docetaxel patients. A safety evaluation will be performed after these first three patients in each chemotherapy arm have been treated to evaluate safety (i.e. toxicity). Based up

Primary Outcome(s)

Irinotecan and metabolite pharmacokinetics, course 1 and 2
Docetaxel pharmacokinetics, course 1 and 2.

Secondary Outcome(s)

Hematological toxicity course 1 and 2.

Secondary ID(s)

ISRCTN72088851

N/A

Source(s) of Monetary Support

Erasmus Medical Center -Daniel den Hoed kliniek, afdeling Interne Oncologie