REDEX: Reducing Dexamethasone Around Docetaxel Infusion

• Sponsor: Leiden University Medical Center (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT02776436
• Collaborator: (none)
• Enrollment: 46
• Locations: 3
• Arms: 2
• Anticipated Duration (Months): 64
• Patients Per Site: 15.3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer; Prostate Cancer	Drug: Dexamethasone; Drug: Prednisone	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 46 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Jan 1, 2016
• Actual Primary Completion Date: Nov 20, 2020
• Anticipated Study Completion Date: May 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Breast cancer 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; Dose of prophylactic dexamethasone will be reduced for all patients; Other Names: dexa
Experimental: Prostate cancer 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; Dose of prophylactic dexamethasone will be reduced for all patients; Other Names: dexa ; Drug: Prednisone; standard prednisone 5 mg bid for patients with prostate cancer; Other Names: prednison

Outcome Measures

Primary Outcome Measures

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. [up to 30 weeks]

   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.

Secondary Outcome Measures

1. Glucose (mmol/L) response due to prophylactic dexamethasone on day 0 before chemotherapy. [up to 30 weeks]

2. Insulin(mU/L), response due to prophylactic dexamethasone on day 0 before chemotherapy. [up to 30 weeks]

3. IGF-1(nmol/L) response due to prophylactic dexamethasone on day 0 before chemotherapy. [up to 30 weeks]

4. Number of participants with toxicity of chemotherapy according to NCI CTCAE v4.03 compared in each dose level of dexamethasone. [up to 30 weeks]

5. Patient's quality of life (descriptive). [up to 30 weeks]

6. Number of patients with single nucleotide polymorphisms in the glucocorticoid receptor. [one week]

Other Outcome Measures

1. The effect of dexamethasone on the Maximum concentration of docetaxel (Cmax) [24 hours]

2. The effect of dexamethasone on Area under the plasma-time concentration curve (AUC) of docetaxel. [24 hours]

3. The effect of dexamethasone on Elimination half-lives of docetaxel (T½,α; T½,β; T½,ƴ) of docetaxel. [24 hours]

4. The effect of dexamethasone on Total body clearance of docetaxel (Cl) of docetaxel. [24 hours]

5. The effect of dexamethasone on Volume of distribution of docetaxel at steady state (Vdss) [24 hours]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Reinier de Graaf hospital	Delft		Netherlands
2	Haga hospital	Den Haag		Netherlands
3	Leiden university medical center	Leiden		Netherlands

Sponsors and Collaborators

• Leiden University Medical Center

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: J.R. Kroep, J.R. Kroep, MD, PhD, Leiden University Medical Center
• ClinicalTrials.gov Identifier: NCT02776436
• Other Study ID Numbers: p15.157; 2015-000718-22
• First Posted: May 18, 2016
• Last Update Posted: Apr 2, 2021
• Last Verified: Mar 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Breast Neoplasms; Prostatic Neoplasms; Dexamethasone; Prednisone

Study Results

No Results Posted as of Apr 2, 2021