Dexamethasone Regimens for Prophylaxis of Paclitaxel-associated Hypersensitivity Reaction

NCT ID: NCT02349763

Last Updated: 2020-10-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 260 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-02-28
• Study Completion Date: 2015-08-30

Brief Summary

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.

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.

Conditions

Hypersensitivity Reaction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

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

Group Type: ACTIVE_COMPARATOR

Oral Dexamethasone

Intervention Type: DRUG

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

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

Group Type: EXPERIMENTAL

Intravenous Dexamethasone

Intervention Type: DRUG

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

Interventions

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

Intervention Type: 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

Intervention Type: DRUG

Other Intervention Names

Dexazone; Dexazone

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Chulalongkorn University

OTHER

Sponsor Role: collaborator

Department of Medical Services Ministry of Public Health of Thailand

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dr Marut Yanaranop, MD

Role: PRINCIPAL_INVESTIGATOR

Department of Medical Services Ministry of Public Health of Thailand

Locations

Rajavithi Hospital

Bangkok, , Thailand

Countries

Thailand

Other Identifiers

pHSR01

Identifier Type: -

Identifier Source: org_study_id