Clinical trial NCT02776436: Reducing Dexamethasone Around Docetaxel Infusion
Official title: Phase 1 Study to Evaluate the Safety of REducing the Prophylactic Dose of DEXamethasone Around Docetaxel Infusion in Patients With Early or Advanced Breast Cancer and Prostate Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Breast Cancer
Prostate Cancer
Lead sponsor: Leiden University Medical Center
Sponsor class: OTHER
First posted: 2016-05-18
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The manufacturer recommends two different regimens of prophylactic dexamethasone to prevent hypersensitivity and fluid retention reactions caused by docetaxel: a 3-day regime of dexamethasone 8mg twice a day starting the day before chemotherapy for breast cancer and for prostate cancer 3 times 8mg dexamethasone on the day of docetaxel infusion, given the concurrent use of prednisone 2dd5mg. There is little evidence that supports this high dose regimen used nowadays. There is need to re-evaluate this high dosage of dexamethasone for three main reasons. First, dexamethasone can give side effects such as manifestation of latent diabetes mellitus, immunosuppression, personality changes, irritability, euphoria, or mania and mood swings. Second, dexamethasone is an immune suppressor, which might inhibit chemotherapy-induced apoptosis and compromise the efficacy of chemotherapeutic agents. Third, dexamethasone is a CYP3A4 inducer, which might increase docetaxel clearance. This study aims to evaluate the feasibility of reducing prophylactic of dexamethasone around docetaxel infusion.


Eligibility criteria: Inclusion Criteria:

* Patients with early breast cancer, or advanced breast cancer or prostate cancer patients receiving docetaxel (minimal 3 cycles monotherapy or in the regimen 4xAC \> 4xdocetaxel or 3xFEC\>3xdocetaxel or 6xTAC)
* Age ≥18 years
* WHO performance status 0-2
* Adequate bone marrow function: white blood cells (WBCs) ≥3.0 x 109/l, neutrophils ≥1.5 x 109/l, platelets ≥100 x 109/l
* Adequate liver function: bilirubin ≤1.5 x upper limit of normal (UNL) range, ALAT and/or ASAT ≤2.5 x UNL (\<5 x UNL in case of liver metastases), Alkaline Phosphatase ≤5 x UNL
* Adequate renal function: the calculated creatinine clearance should be ≥50 mL/min
* Survival expectation must be \> 3 months
* Written informed consent according to the local Ethics Committee requirements

Exclusion Criteria:

* Known hypersensitivity for docetaxel, paclitaxel or other chemotherapeutic agent or products containing polysorbate 80 or an earlier experience of anaphylaxis for food, insect bites, medication or another foreign substance.
* Existence of edema of the limbs or trunk or elsewhere localized.
* Active second malignancy
* Diabetes Mellitus
* Serious other diseases such as recent myocardial infarction (last 6 months), clinical signs of cardiac failure or clinically significant arrhythmias
* Female patients who are pregnant or breast-feeding
* Medical or psychological condition which in the opinion of the investigator would not permit the patient to complete the study or sign meaningful informed consent

Primary outcomes:
measure: Optimal dose/recommended dose (RD) of pre-medication dexamethasone around docetaxel infusion, dependent of occurrence of grade III/IV fluid retention and HSR according to the NCI CTCAE v4.03.
timeFrame: up to 30 weeks
Secondary outcomes:
measure: Glucose (mmol/L) response due to prophylactic dexamethasone on day 0 before chemotherapy.
timeFrame: up to 30 weeks
measure: Insulin(mU/L), response due to prophylactic dexamethasone on day 0 before chemotherapy.
timeFrame: up to 30 weeks
measure: IGF-1(nmol/L) response due to prophylactic dexamethasone on day 0 before chemotherapy.
timeFrame: up to 30 weeks
measure: Number of participants with toxicity of chemotherapy according to NCI CTCAE v4.03 compared in each dose level of dexamethasone.
timeFrame: up to 30 weeks
measure: Patient's quality of life (descriptive).
timeFrame: up to 30 weeks
measure: Number of patients with single nucleotide polymorphisms in the glucocorticoid receptor.
timeFrame: one week
Other outcomes:
measure: The effect of dexamethasone on the Maximum concentration of docetaxel (Cmax)
timeFrame: 24 hours
measure: The effect of dexamethasone on Area under the plasma-time concentration curve (AUC) of docetaxel.
timeFrame: 24 hours
measure: The effect of dexamethasone on Elimination half-lives of docetaxel (T½,α; T½,β; T½,ƴ) of docetaxel.
timeFrame: 24 hours
measure: The effect of dexamethasone on Total body clearance of docetaxel (Cl) of docetaxel.
timeFrame: 24 hours
measure: The effect of dexamethasone on Volume of distribution of docetaxel at steady state (Vdss)
timeFrame: 24 hours
Locations:
city: Delft
country: Netherlands
facility: Reinier de Graaf hospital
city: Den Haag
country: Netherlands
facility: Haga hospital
city: Leiden
country: Netherlands
facility: Leiden university medical center
Study officials:
References: