Dexamethasone Regimens for Prophylaxis of Paclitaxel-associated Hypersensitivity Reaction (DEPARO)

Intravenous Versus Oral Regimens of Dexamethasone for Prophylaxis of Paclitaxel-associated Hypersensitivity Reaction in Primary Ovarian, Fallopian Tube and Peritoneal Cancer Patients: a Double-blind Randomized Controlled Trial

Comparison of the efficacy and side effects of intravenous and oral regimens of dexamethasone for prophylaxis of paclitaxel-associated hypersensitivity reactions in primary ovarian, fallopian tube and peritoneal cancer patients receiving first cycle of combination paclitaxel and carboplatin.

Study Overview

• Status: Completed
• Conditions: Hypersensitivity Reaction
• Intervention / Treatment: Drug: Oral Dexamethasone; Drug: Intravenous Dexamethasone

Detailed Description

The consensus statements on the management of ovarian cancer recommended intravenous paclitaxel (175 mg/m2 over 3 hr) plus intravenous carboplatin (area under the curve [AUC] 5.0-7.5 mg/ml∙min) given every 3 weeks for six cycles for first-line chemotherapy. A major limitation of paclitaxel was its poor water solubility, which led to the use of polyoxyethylated castor oil vehicle or Cremophor® EL as diluents resulted a hypersensitivity reactions (HSRs). Initial P-HSRs generally occur within 10 minutes of the start of paclitaxel infusion and most occur with the first or second infusion. Majority of patients manifest as minor symptoms characterized by flushing and rashes but sometime life-threatening characterized by generalized urticaria, angioedema, bronchospasm and hypertension or until fatal may occur. The reaction is likely due to the release of histamine and other vasoactive substances in response to Cremophor EL. Originally, the prophylactic regimen composed of the use of an oral corticosteroid administered in two doses at 12 and 6 hours prior to paclitaxel infusion accompanied with histamine receptor H1 and H2 antagonists administered intravenously 30 minutes prior to paclitaxel infusion was found to successfully limit P-HSRs denoted as "Conventional oral prophylactic regimen".

While this three-drug prophylactic regimen has been shown to be effective, it can be inconvenient for patients because the oral corticosteroid must be taken 12 and 6 hours before chemotherapy administration. If the patient forgets to take one or both pretreatment steroid doses, it is not clear whether the patient can be safely treated. This led to the experimental prophylactic regimen of one dose of intravenous dexamethasone accompanied with the H1 and H2 antagonists administered 30 minutes prior to paclitaxel infusion was subsequently reported to be equivalent to the regimen of oral dexamethasone denoted as "Modified intravenous prophylactic regimen". This intravenous regimen results in lower total steroid doses and precludes the issues of compliance.

• Study Type: Interventional
• Enrollment (Actual): 260
• Phase: Phase 3

Contacts and Locations

Study Locations

• Thailand
  • Bangkok, Thailand, 10400
    • Rajavithi Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Patient pathologically diagnosed with primary ovarian or fallopian tube or peritoneal cancer
• Patient starting a first cycle of combination paclitaxel and carboplatin at Rajavithi Hospital between February 1, 2015 and July 31, 2015
• Patient aged 18-70 years
• Patient with ECOG performance status 0-2
• Patient with the following laboratory values obtained: Hemoglobin > 10 g/dL, Absolute neutrophil count > 1500 /mm3, Platelet count > 100,000/mm3, Serum creatinine > 2.0 mg/dL, Bilirubin > 1.5 x ULN, alkaline phosphatase and SGOT > 3 x ULN
• Patient able to give free and informed consent and who agrees to participate by signing the consent form
• Patient able to speak and understand Thai
• Patient able to complete the quality of life questionnaire on Functional Assessment of Cancer Therapy - Ovarian Cancer (FACT-O) Thai version 4.0 and the personal logbook

Exclusion Criteria:

• Patient who has previously received paclitaxel or carboplatin
• Patient receiving an albumin-bound paclitaxel
• Patient who had an allergic reaction to taxanes or platinum analogues
• Patient is currently under treatment with systemic corticosteroids or has received systemic corticosteroids or histamine antagonists during the last week
• Patient who had an allergic reaction to corticosteroid or diphenhydramine or ranitidine
• Patient with severe intolerance to lactose
• Patient with an allergy or a severe intolerance to products containing castor oil e.g. cyclosporine, teniposide, diazepam, propofol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Oral Dexamethasone; Dexamethasone 20 mg (4 mg/tablet) or 5 tablets given orally at 12 and 6 hours before paclitaxel infusion and 0.9% NaCL (Placebo) 4 ml given intravenously at 30 minutes before paclitaxel infusion	Drug: Oral Dexamethasone; Dexamethasone 20 mg (4 mg/tablet) or 5 tablets given orally at 12 and 6 hours before paclitaxel infusion and 0.9% NaCL (Placebo) 4 ml given intravenously at 30 minutes before paclitaxel infusion; Other Names: Dexazone
Experimental: Intravenous Dexamethasone; Lactose (Placebo) 5 tablets given orally at 12 and 6 hours before paclitaxel infusion and dexamethasone 20 mg (5mg/ml) given intravenously at 30 minutes before paclitaxel infusion	Drug: Intravenous Dexamethasone; Lactose (Placebo) 5 tablets given orally at 12 and 6 hours before paclitaxel infusion and dexamethasone 20 mg (5mg/ml) given intravenously at 30 minutes before paclitaxel infusion; Other Names: Dexazone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Paclitaxel-Associated Hypersensitivity Reaction (P-HSRs) and severe P-HSRs (Safety endpoint)	The participants are received either intravenous dexamethasone or placebo (0.9% NaCL) at 09.30 am (30 minutes before paclitaxel infusion) depend on intervention groups. Intravenous ranitidine 50 mg and diphenhydramine 50 mg are also given all participants. Paclitaxel is started at 10.00 am by the calculated dose of is diluted in 500 ml of saline and administered by intravenous infusion over 3 hours.	3 Hours after starting paclitaxel infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of side effects of dexamethasone	All participants receive the personal logbook for self-administration of side effects from dexamethasone in day 1-7	1 week after completion of chemotherapy
Incidence of other Adverse Events ( according to NCI CTCAE version 4.03)	The adverse events are collected according to NCI CTCAE version 4.03.	Adverse events were measured at Day 1 and Day 28 of intervention
Quality of life (QoL) (assessed by FACT-O score)	Quality of life assessed by FACT-O score	QoL is measured at Day 0 and Day 28 of intervention

Collaborators and Investigators

• Sponsor: Rajavithi Hospital
• Collaborators: Chulalongkorn University
• Investigators: Principal Investigator: Dr Marut Yanaranop, MD, Rajavithi Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 28, 2015
• Primary Completion (Actual): July 30, 2015
• Study Completion (Actual): August 30, 2015

Study Registration Dates

• First Submitted: January 23, 2015
• First Submitted That Met QC Criteria: January 28, 2015
• First Posted (Estimate): January 29, 2015

Study Record Updates

• Last Update Posted (Actual): October 23, 2020
• Last Update Submitted That Met QC Criteria: October 21, 2020
• Last Verified: January 1, 2015

More Information

Terms related to this study

• Keywords: Dexamethasone; Paclitaxel; Hypersensitivity reaction
• Additional Relevant MeSH Terms: Immune System Diseases; Hypersensitivity; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protease Inhibitors; Dexamethasone; Dexamethasone acetate; BB 1101
• Other Study ID Numbers: pHSR01