The main objective is: To determine the influence of curcumin with or without piperine, in patients with breast cancer, on endoxifen plasma pharmacokinetics (AUC).Secundary objectives are:1. Other pharmacokinetic outcomes (i.e. clearance, minimum…
ID
Source
Brief title
Condition
- Breast neoplasms malignant and unspecified (incl nipple)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To determine the influence of curcumin with or without piperine, in patients
with breast cancer, on endoxifen plasma pharmacokinetics. The main parameter
will be AUC.
Secondary outcome
1. Other pharmacokinetic outcomes (i.e. clearance, minimum concentration
(Ctrough) and the tamoxifen/endoxifen ratio.
2. To evaluate plasma concentration levels of tamoxifen and other tamoxifen
metabolites
3. To evaluate the incidence and severity of side-effects of treatment with
tamoxifen in absence and presence of curcumin with or without piperine.
Background summary
Nowadays lots of cancer patients use herbal medicine. One of the most popular
herb drugs is curcumin. Curcumin is often used as additional therapy next to
normal clinical practice. Curcumin might influence pharmacokinetics of several
drugs due to inhibition of several cytochrome P450 enzymes such as CYP3A4 and
CYP2D6. It also influences UGT and several in- and efflux pumps such as
P-glycoprotein and OATP.
An example of a drug, which metabolism depends on this enzymes and pumps is
tamoxifen, an estrogen receptor antagonist used by breast cancer patients .
Since curcumin may alter the exposure, and thereby, tamoxifen efficacy it is
important to investigate the clinical significance of this food-drug
interaction.
Because of its low bioavailability curcumin is often administered concomitantly
with piperine, an extract of black pepper. Piperine may increase
bioavailability by inhibition of glucoronidation of curcumin and thereby
potentially increases the effect of curcumin on tamoxifen pharmacokinetics.
Furthermore piperine is believed to have an effect on several metabolizing
enzymes such as CYP 3A4, CYP2C9 and CYP2B6.
The main objective of this study is to evaluate the pharmacokinetics (PK) of
tamoxifen, when concomitantly used with curcumin with or without piperine in
patients with breast cancer.
Study objective
The main objective is: To determine the influence of curcumin with or without
piperine, in patients with breast cancer, on endoxifen plasma pharmacokinetics
(AUC).
Secundary objectives are:
1. Other pharmacokinetic outcomes (i.e. clearance, minimum concentration
(Ctrough) and the tamoxifen/endoxifen ratio.
3. To evaluate plasma concentration levels of tamoxifen and other tamoxifen
metabolites
2. To evaluate the incidence and severity of side-effects of treatment with
tamoxifen in absence and presence of curcumin with or without piperine.
Study design
This is an open label three period exploratory, randomized, cross-over study in
patients taking tamoxifen for breast cancer. This study will be performed at
the Erasmus MC Cancer Institute in Rotterdam, The Netherlands. It is
anticipated that the study will be performed within a 1 year study period after
approval by the institutional ethical board. Before entering the study patients
have to be on steady state tamoxifen plasma levels. To reach steady state
patients have to use tamoxifen (at the same dose) for at least 28 days (run-in
phase).
After reaching steady-state all patients will use tamoxifen alone (phase A) or
with curcumin with or without piperine (phase B and phase C, respectively).
Patients must use curcumin with or without piperine for at least 28 days to
ensure steady-state concentration of curcumin.
Patients will be randomized in two sequence groups, sequence ABC or sequence
CBA to rule out any sequence effects. Patients will be hospitalized on day 28,
56 and 84 for PK blood sampling for 24 hours (PK1, PK2, PK3).
Intervention
Patients will be treated with tamoxifen only and in combination with curcumin
with or without piperine.
Study burden and risks
Patients will be admitted to the hospital for a total of three days, during
which pharmacokinetic blood withdrawals will be performed. Patients will be
randomized into 2 sequence groups consisting of 3 phases. In 2 phases patients
are also treated with curcumin with or without piperine for 28 consecutive
days. Patients do not benefit individually from this study. Major risks to be
expected are side effects of tamoxifen or curcumin and piperine for which
patients will be carefully observed.
's-Gravendijkwal 230
Rotterdam 3015CE
NL
's-Gravendijkwal 230
Rotterdam 3015CE
NL
Listed location countries
Age
Inclusion criteria
1. Age * 18 years;2. Histological or cytological confirmed diagnosis of breast cancer in patients with an indication for tamoxifen treatment.;3. WHO Performance Status * 1 ;4. Able and willing to sign the Informed Consent Form prior to screening evaluations;5. Abstain from curry, grapefruit (juice), (herbal) dietary supplements besides curcumin, herbals, over-the-counter medication (except for paracetamol and ibuprofen).;6. Adequate baseline patient characteristics (complete blood count, and serum biochemistry which involves sodium, potassium, creatinin, calculation of creatinin clearance (MDRD), AST, ALT, gamma glutamyltranspeptidase (GGT), lactate dehydrogenase (LDH), ALP, total bilirubin, albumin).
Exclusion criteria
1. Pregnant or lactating patients.;2. Patients with known impaired drug absorption (e.g. gastrectomy and achlorhydria).;3. Use of other drugs, which are mainly dependent for their metabolism on CYP3A4 and CYP2D6. ;4. Known serious illness or medical unstable conditions that could interfere with this study; requiring treatment (e.g. infection, bleedings, uncontrolled hypertension despite optimal medical management, HIV, hepatitis, organ transplants, kidney, cardiac and respiratory diseases).;5. Bilirubin CTCAE grade 2 or higher, ASAT/ALAT CTCAE grade 2 or higher and grade 3 or higher in patients with liver metastasis. . Renal function impairment CTCAE grade 2 or higher.;6. Symptomatic CNS metastases or history of psychiatric disorder that would prohibit the understanding and giving of informed consent.;7. Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation. ;8. Patients on strong CYP3A4 or CYP2D6 inhibitors or inducers, P-gp substrates or medication or supplements which can interact with tamoxifen and curcumin are not eligible for the study.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
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In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2016-004008-71-NL |
| CCMO | NL59496.078.16 |