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Reducing Dexamethasone Around Docetaxel Infusion (REDEX)

Primary Purpose

Breast Cancer, Prostate Cancer

Status
Unknown status
Phase
Phase 1
Locations
Netherlands
Study Type
Interventional
Intervention
Dexamethasone
Prednisone
Sponsored by
Leiden University Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Breast Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Reinier de Graaf hospital
  • Haga hospital
  • Leiden university medical center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Breast cancer

Prostate cancer

Arm Description

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)

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)

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Glucose (mmol/L) response due to prophylactic dexamethasone on day 0 before chemotherapy.
Insulin(mU/L), response due to prophylactic dexamethasone on day 0 before chemotherapy.
IGF-1(nmol/L) response due to prophylactic dexamethasone on day 0 before chemotherapy.
Number of participants with toxicity of chemotherapy according to NCI CTCAE v4.03 compared in each dose level of dexamethasone.
Patient's quality of life (descriptive).
Number of patients with single nucleotide polymorphisms in the glucocorticoid receptor.

Full Information

First Posted
January 25, 2016
Last Updated
March 30, 2021
Sponsor
Leiden University Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT02776436
Brief Title
Reducing Dexamethasone Around Docetaxel Infusion
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2021
Overall Recruitment Status
Unknown status
Study Start Date
January 2016 (Actual)
Primary Completion Date
November 20, 2020 (Actual)
Study Completion Date
May 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Leiden University Medical Center

4. Oversight

Data Monitoring Committee
No

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer, Prostate Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
46 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Breast cancer
Arm Type
Experimental
Arm Description
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)
Arm Title
Prostate cancer
Arm Type
Experimental
Arm Description
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)
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Other Intervention Name(s)
dexa
Intervention Description
Dose of prophylactic dexamethasone will be reduced for all patients
Intervention Type
Drug
Intervention Name(s)
Prednisone
Other Intervention Name(s)
prednison
Intervention Description
standard prednisone 5 mg bid for patients with prostate cancer
Primary Outcome Measure Information:
Title
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.
Description
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.
Time Frame
up to 30 weeks
Secondary Outcome Measure Information:
Title
Glucose (mmol/L) response due to prophylactic dexamethasone on day 0 before chemotherapy.
Time Frame
up to 30 weeks
Title
Insulin(mU/L), response due to prophylactic dexamethasone on day 0 before chemotherapy.
Time Frame
up to 30 weeks
Title
IGF-1(nmol/L) response due to prophylactic dexamethasone on day 0 before chemotherapy.
Time Frame
up to 30 weeks
Title
Number of participants with toxicity of chemotherapy according to NCI CTCAE v4.03 compared in each dose level of dexamethasone.
Time Frame
up to 30 weeks
Title
Patient's quality of life (descriptive).
Time Frame
up to 30 weeks
Title
Number of patients with single nucleotide polymorphisms in the glucocorticoid receptor.
Time Frame
one week
Other Pre-specified Outcome Measures:
Title
The effect of dexamethasone on the Maximum concentration of docetaxel (Cmax)
Time Frame
24 hours
Title
The effect of dexamethasone on Area under the plasma-time concentration curve (AUC) of docetaxel.
Time Frame
24 hours
Title
The effect of dexamethasone on Elimination half-lives of docetaxel (T½,α; T½,β; T½,ƴ) of docetaxel.
Time Frame
24 hours
Title
The effect of dexamethasone on Total body clearance of docetaxel (Cl) of docetaxel.
Time Frame
24 hours
Title
The effect of dexamethasone on Volume of distribution of docetaxel at steady state (Vdss)
Time Frame
24 hours

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Facility Information:
Facility Name
Reinier de Graaf hospital
City
Delft
Country
Netherlands
Facility Name
Haga hospital
City
Den Haag
Country
Netherlands
Facility Name
Leiden university medical center
City
Leiden
Country
Netherlands

12. IPD Sharing Statement

Plan to Share IPD
No

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Reducing Dexamethasone Around Docetaxel Infusion

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