Reducing Dexamethasone Around Docetaxel Infusion

NCT02776436 | Completed Phase 1

• 2 other identifiers: p15.1572015-000718-22
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 3

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.

Conditions

Breast Cancer; Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Glucose (mmol/L) response due to prophylactic dexamethasone on day 0 before chemotherapy.

  up to 30 weeks

• Insulin(mU/L), response due to prophylactic dexamethasone on day 0 before chemotherapy.

  up to 30 weeks

• IGF-1(nmol/L) response due to prophylactic dexamethasone on day 0 before chemotherapy.

  up to 30 weeks

• Number of participants with toxicity of chemotherapy according to NCI CTCAE v4.03 compared in each dose level of dexamethasone.

  up to 30 weeks

• Patient's quality of life (descriptive).

  up to 30 weeks

Other Outcomes (5)

• The effect of dexamethasone on the Maximum concentration of docetaxel (Cmax)

  24 hours

• The effect of dexamethasone on Area under the plasma-time concentration curve (AUC) of docetaxel.

  24 hours

• The effect of dexamethasone on Elimination half-lives of docetaxel (T½,α; T½,β; T½,ƴ) of docetaxel.

  24 hours

Study Arms (2)

Breast cancer

EXPERIMENTAL

Dose of prophylactic dexamethasone will be reduced as follows: STEP 1: 12 mg dexamethasone per day (8-4mg/day) for 3 days starting 1 day before administration. (n=6) STEP 2: 8mg dexamethasone per day (8mg once a day) for 3 days starting 1 day before administration. (n=6) STEP 3: day -1: 4 mg, day 0: 8 mg, day 1: 4 mg. (n=6) STEP 4: day -1: 0 mg, day 0: 8 mg, day 1: 4 mg. (n=6) STEP 5: day -1: 0 mg, day 0: 8 mg, day 1: 0 mg. (n=6) STEP 6: day -1: 0 mg, day 0: 4 mg, day 1: 0 mg. (n=6)

Drug: Dexamethasone

Prostate cancer

EXPERIMENTAL

Dose of prophylactic dexamethasone will be reduced as follows: STEP 1: 2dd 8 mg at 12 and 1 hr before treatment (besides standard prednisone 5mg bid) (n=6) STEP 2: 8mg dexamethasone 1 hour before treatment (and standard prednisone 5mg bid). (n=6) STEP 3: 4mg dexamethasone 1 hour before treatment (and standard prednisone 5mg bid). (n=6) STEP 4: 0mg dexamethasone (only standard prednisone 5mg bid). (n=6)

Drug: Dexamethasone; Drug: Prednisone

Interventions

Dexamethasone DRUG

Dose of prophylactic dexamethasone will be reduced for all patients

Also known as: dexa

Breast cancer; Prostate cancer

Prednisone DRUG

standard prednisone 5 mg bid for patients with prostate cancer

Also known as: prednison

Prostate cancer

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Leiden University Medical Center: lead

Study Sites (3)

Reinier de Graaf hospital

Delft, Netherlands

Location

Leiden university medical center

Leiden, Netherlands

Location

Haga hospital

The Hague, Netherlands

Location

MeSH Terms

Conditions

Breast Neoplasms; Prostatic Neoplasms

Interventions

Dexamethasone; Absorptiometry, Photon; Prednisone

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Radiography; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Densitometry; Photometry; Chemistry Techniques, Analytical; Investigative Techniques; Pregnadienediols

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: J.R. Kroep, MD, PhD

Study Record Dates

• First Submitted: January 25, 2016
• First Posted: May 18, 2016
• Study Start: January 1, 2016
• Primary Completion: November 20, 2020
• Study Completion: November 20, 2020
• Last Updated: February 17, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

NL (3)