Reducing Dexamethasone Around Docetaxel Infusion

Breast Cancer Clinical Trial

— REDEX  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02776436
• Other study ID #: p15.157
• Secondary ID: 2015-000718-22
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: January 2016
• Est. completion date: May 2021

Study information

• Verified date: March 2021
• Source: Leiden University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 46
• Est. completion date: May 2021
• Est. primary completion date: November 20, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• Dexamethasone
Dose of prophylactic dexamethasone will be reduced for all patients
• Prednisone
standard prednisone 5 mg bid for patients with prostate cancer

Locations

Country	Name	City	State
Netherlands	Reinier de Graaf hospital	Delft
Netherlands	Haga hospital	Den Haag
Netherlands	Leiden university medical center	Leiden

Sponsors (1)

Lead Sponsor	Collaborator
Leiden University Medical Center

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	The effect of dexamethasone on the Maximum concentration of docetaxel (Cmax)		24 hours
Other	The effect of dexamethasone on Area under the plasma-time concentration curve (AUC) of docetaxel.		24 hours
Other	The effect of dexamethasone on Elimination half-lives of docetaxel (T½,a; T½,ß; T½,?) of docetaxel.		24 hours
Other	The effect of dexamethasone on Total body clearance of docetaxel (Cl) of docetaxel.		24 hours
Other	The effect of dexamethasone on Volume of distribution of docetaxel at steady state (Vdss)		24 hours
Primary	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.	If one grade III/IV HSR or fluid retention reaction occurs in one of the six patients within one cohort, then three additional patients will be treated at that dose level. If there are no additional grade III/IV HSR or fluid retention in that additional 3 patients accrual to the next lower dose level will be started. If a grade III/IV HSR or fluid retention occurs in at least 2/6 or 2/9 patients, that dose will not be tolerated as safe and the last previous dose level of dexamethasone will be the RD.	up to 30 weeks
Secondary	Glucose (mmol/L) response due to prophylactic dexamethasone on day 0 before chemotherapy.		up to 30 weeks
Secondary	Insulin(mU/L), response due to prophylactic dexamethasone on day 0 before chemotherapy.		up to 30 weeks
Secondary	IGF-1(nmol/L) response due to prophylactic dexamethasone on day 0 before chemotherapy.		up to 30 weeks
Secondary	Number of participants with toxicity of chemotherapy according to NCI CTCAE v4.03 compared in each dose level of dexamethasone.		up to 30 weeks
Secondary	Patient's quality of life (descriptive).		up to 30 weeks
Secondary	Number of patients with single nucleotide polymorphisms in the glucocorticoid receptor.		one week