• To determine pharmacokinetic interactions between St. John*s wort and docetaxel and between echinacea and docetaxel in patients with cancer.• To determine the safety of the use of St. John*s wort or echinacea in combination with docetaxel.• To…
ID
Source
Brief title
Condition
- Miscellaneous and site unspecified neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The most important parameter is the concentration of docetaxel and the course
of this concentration with time in the presence or absence of St. John's Wort
or echinacea
Secondary outcome
Secondary parameters are toxicities that patients experience from docetaxel in
the presence or absence of St. John's Wort or echinacea
Background summary
The use of complementary and alternative medicines (CAM) by cancer patients has
increased during the last years and we hypothesize that CAM-anticancer drugs
interactions can explain unexpected clinical toxicities and undertreatment of
chemotherapy in cancer patients.
So far, some clinical studies have been conducted to investigate the clinical
significance of the interactions between anticancer drugs, like irinotecan and
imatinib, and the CAM St. John*s wort. These studies showed serious
pharmacokinetic interactions with co-administration of St. John*s wort, because
these co-administrations resulted in a significant decrease in plasma
concentration of irinotecan and an increase in the clearance of imatinib. Like
irinotecan and imatinib, docetaxel is metabolised by CYP3A4. As CYP3A4 is the
main mediator of this interaction, it is expected that co-administration of St.
John*s wort leads to a clinical effect on the pharmacokinetics of docetaxel.
However, no study has been conducted to examine the pharmacokinetics of
docetaxel with co-administration of St. John*s wort.
In vitro assays, performed in our laboratory, have shown that echinacea induces
the activity of hepatic CYP3A4, which may result in an undertreatment of cancer
patients. However, no studies have been performed to examine the
pharmacokinetics of docetaxel with co-administration of echinacea.
Therefore, it is essential to perform a study on the pharmacokinetic
interactions between St. John*s wort and docetaxel and to compare this with
echinacea and docetaxel in cancer patients.
Study objective
• To determine pharmacokinetic interactions between St. John*s wort and
docetaxel and between echinacea and docetaxel in patients with cancer.
• To determine the safety of the use of St. John*s wort or echinacea in
combination with docetaxel.
• To establish guidelines to prevent unwanted interactions between
complementary, alternative medicines, like St. John*s wort and echinacea, and
anticancer drugs in patients.
Study design
Cohort A:
Cycle 1 starts with docetaxel as an absolute dose of 135 mg given as a 60 min.
intravenous administration on day 1. The dose of 135 mg is based on a safe dose
of 75 mg/m2 and a mean BSA of 1.8 m2. St. John*s wort will be given as 20 drops
of the officially registered oral solution three times daily on day -14 until
day 1 of cycle 2. The last administration of St. John*s wort will be on the
morning of day 1. This will be followed by docetaxel as an absolute dose of 135
mg, given as a 60 min. intravenous administration on day 1 of cycle 2. A wash
out period of 3 weeks will follow after day 1 of cycle 2, to recover from the
enzyme induction by St. John*s wort.
Cohort B:
Cycle 1 starts with docetaxel as an absolute dose of 135 mg given as a 60 min.
intravenous administration on day 1. Echinacea will be given as 20 drops of the
officially registered oral solution three times daily on day -14 until day 1 of
cycle 2. The last administration of echinacea will be on the morning of day 1.
This will be followed by docetaxel as an absolute dose of 135 mg, given as a 60
min. intravenous administration on day 1 of cycle 2. A wash out period of 3
weeks will follow after day 1 of cycle 2, to recover from the enzyme induction
by echinacea.
Intervention
Administration of 135 mg docetaxel on day 1 of cycle 1 and 2
Administration of 3 times daily 20 drops St. John' Wort or echinacea on day -14
to day 1 of cycle 2
2x 24 hour hospital admission with blood sampling for pharmacokinetics
3x visit with physical examination and blood sampling for safety
Study burden and risks
Administration of 135 mg docetaxel on day 1 of cycle 1 and 2
Administration of 20 drops of St. John's Wort or echinacea 3 times a day on day
-14 to day 1 of cycle 2
2x 24 hour hospital admission with blood sampling for pharmacokinetrics
3x visit with physical examination and blood sampling for safety
Toxiciteities of docetaxel will also be experienced by patients when they do
not participate in the study.
No toxicities of St. John's Wort or echinacea are to be expected.
There is a small risk of bruising by blood sampling.
Plesmanlaan 121
1066 CX
Amsterdam
Plesmanlaan 121
1066 CX
Amsterdam
Listed location countries
Age
Inclusion criteria
1. Patients for whom treatment with docetaxel is considered to be of therapeutic benefit, e.g. advanced breast, gastric, esophagus, bladder, ovarian cancer and non-small cell lung cancer, head and neck cancer and prostate cancer
2. Histological or cytological proof of malignancy
3. Age >=18 years
4. Performance: WHO <= 2
5. Life expectancy > 3 months allowing adequate follow up of toxicity evaluation and anti-tumor activity
6. Minimal acceptable safety laboratory values:
a) ANC of >= 1.5 × 109/L
b) Platelet count of >= 100 × 109/L
c) Haemoglobin level of >= 6.0 mmol/L
(prior transfusion is permitted)
d) Hepatic function as defined by serum bilirubin <= 1.5 times the upper limit of normal (ULN), ALT and AST <= 2.5 times the ULN
e) Renal function as defined by serum creatinine <= 1.5 times ULN or creatinine clearance >= 50 mL/min (by Cockcroft-Gault formula)
7. Able and willing to swallow and retain oral medication.
8. Able and willing to undergo blood sampling for pharmacokinetics
9. Willing to comply to the protocol and to follow dietary restrictions
10. Written informed consent.
Exclusion criteria
1. Any treatment with investigation drugs within 30 days before the start of the study
2. Patients with known alcoholism, drug addiction and/or a history of psychotic disorders that are not suitable for adequate follow up
3. Men enrolled in this trial must agree to use a reliable contraceptive method throughout the study (adequate contraceptive methods are: condom, contraceptive pill (female partner), abstinence from sexual intercourse, sterilisation of man or woman).
4. Concomitant use of MDR and CYP3A modulating drugs such as Ca¬¬+-entry blockers (verapamil, dihydropyridines), cyclosporine, quinidine, quinine, tamoxifen, megestrol and grapefruit juice, concomitant use of HIV medications; other protease inhibitors, (non) nucleoside analogs, or St. Johns wort.
5. Uncontrolled infectious disease or known HIV-1 or HIV-2 type patients
6. Unresolved (>grade 1) toxicities of previous chemotherapy
7. Bowel obstruction or motility disorders that may influence the absorption of drugs
8. Chronic use of H2-receptor antagonists or proton pump inhibitors
9. Neurologic disease that may render a patient at increased risk for peripheral or central neurotoxicity
10. Symptomatic cerebral or leptomeningeal metastases
11. Use of herbal supplements, especially St. John*s wort or echinacea, within 6 weeks prior to study treatment.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2008-000886-41-NL |
| CCMO | NL25100.031.08 |